57 results on '"Phase II trial"'
Search Results
2. Safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination in stage IV non-small-cell lung cancer: An open-label phase II trial (VinMetAtezo).
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Vergnenegre, Alain, Monnet, Isabelle, Ricordel, Charles, Bizieux, Acya, Curcio, Hubert, Bernardi, Marie, Corre, Romain, Guisier, Florian, Hominal, Stéphane, Le Garff, Gwenaelle, Bylicki, Olivier, Locher, Chrystèle, Geier, Margaux, Chouaïd, Christos, and Robinet, Gilles
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NON-small-cell lung carcinoma , *CLINICAL trials , *IMMUNE checkpoint inhibitors - Abstract
• 2nd-line metronomic oral vinorelbine-atezolizumab in advanced NSCLC was assessed. • 4-month PFS rate was 32%; median PFS and OS were 2.2 and 7.9 months, respectively. • The predefined PFS threshold was not achieved. • No new safety signal was reported for the vinorelbine-atezolizumab combination. To evaluate the safety and efficacy of second-line metronomic oral vinorelbine–atezolizumab combination for stage IV non-small-cell lung cancer. This was a multicenter, open-label, single-arm Phase II study performed in patients with advanced NSCLC without activating EGFR mutation or ALK rearrangement who progressed after first-line platinum-doublet chemotherapy. Combination treatment was atezolizumab (1200 mg IV day 1, every 3 weeks) and oral vinorelbine (40 mg, 3 times by week). The primary outcome was progression-free survival (PFS) during the 4-month follow-up from the first dose of treatment. Statistical analysis was based on the exact single-stage Phase II design defined by A'Hern. Based on literature data, the Phase III trial threshold was set at 36 successes in 71 patients. 71 patients were analyzed (median age, 64 years; male, 66.2%; ex-smokers/active smokers, 85.9%; ECOG performance status 0–1, 90.2%; non-squamous NSCLC, 83.1%; PD-L1 ≥ 50%, 4.4%). After a median follow-up of 8.1 months from treatment initiation, 4-month PFS rate was 32% (95% CI, 22–44), i.e. 23 successes out 71 patients. OS rate was 73.2% at 4 months and 24.3% at 24 months. Median PFS and OS were 2.2 (95% CI, 1.5–3.0) months and 7.9 (95% CI, 4.8–11.4) months, respectively. Overall response rate and disease control rate at 4 months were 11% (95% CI, 5–21) and 32% (95% CI, 22–44), respectively. No safety signal was evidenced. Metronomic oral vinorelbine-atezolizumab in the second-line setting did not achieve the predefined PFS threshold. No new safety signal was reported for vinorelbine-atezolizumab combination. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study.
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Longo-Muñoz, Federico, Castellano, Daniel, Alexandre, Jerome, Chawla, Sant P., Fernández, Cristian, Kahatt, Carmen, Alfaro, Vicente, Siguero, Mariano, Zeaiter, Ali, Moreno, Victor, Sanz-García, Enrique, Awada, Ahmad, Santaballa, Ana, and Subbiah, Vivek
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THERAPEUTIC use of antineoplastic agents , *CONFIDENCE intervals , *FEBRILE neutropenia , *CANCER patients , *TREATMENT effectiveness , *NEUROENDOCRINE tumors , *ODDS ratio , *PROGRESSION-free survival - Abstract
Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy. This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks in 32 NETs patients treated in the second- or third-line setting. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1 assessed by the investigators. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8–21.4%). Median DoR was 4.7 months (95% CI, 4.0–5.4 months), median PFS was 1.4 months (95% CI, 1.2–3.0 months) and median OS was 7.4 months (95% CI, 3.4–16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%). Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population. Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42. ClinicalTrials.gov reference: NCT02454972. • ORR with lurbinectedin in patients with NETs was 6.5% (95%CI, 0.8–21.4%). • Median DoR, PFS and OS were 4.7, 1.4 and 7.4 months, respectively. • Safety profile was predictable and manageable. • Development of lurbinectedin in a selected NETs population is warranted. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Hypofractionated proton and carbon ion beam radiotherapy for sacrococcygeal chordoma (ISAC): An open label, randomized, stratified, phase II trial.
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Seidensaal, Katharina, Froehlke, Andreas, Lentz-Hommertgen, Adriane, Lehner, Burkhard, Geisbuesch, Andreas, Meis, Jan, Liermann, Jakob, Kudak, Andreas, Stein, Katharina, Uhl, Matthias, Tessonnier, Thomas, Mairani, Andrea, Debus, Juergen, and Herfarth, Klaus
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ION beams , *OVERALL survival , *PROTON therapy , *PROGRESSION-free survival , *DOSE fractionation , *CHORDOMA , *RADIOTHERAPY - Abstract
• Phase II study on safety and feasibility of hypofractionated proton and carbon ion beam therapy for sacrococcygeal chordomas. • The trial enrolled 82 patients, achieving 96% 2-year and 81% 4-year overall survival rates. • Local progression-free survival rates were 84% at 2 years and 70% at 4 years. • The treatment with carbon ions or protons was delivered in 16 fractions of 4 Gy RBE over 5-6 fractions per week. • No significant differences were observed between the proton and carbon ion therapy groups with this distinct fractionation scheme. Sacrococcygeal chordomas have high recurrence rates and are challenging to treat. In this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3–5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). The study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5–6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). The initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma. [ABSTRACT FROM AUTHOR]
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- 2024
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5. A randomized phase II trial of Captem or Folfiri as second-line therapy in neuroendocrine carcinomas.
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Bongiovanni, Alberto, Liverani, Chiara, Foca, Flavia, Bergamo, Francesca, Leo, Silvana, Pusceddu, Sara, Gelsomino, Fabio, Brizzi, Maria Pia, Di Meglio, Giovanni, Spada, Francesca, Tamberi, Stefano, Lolli, Ivan, Cives, Mauro, Marconcini, Riccardo, Pucci, Francesca, Berardi, Rossana, Antonuzzo, Lorenzo, Badalamenti, Giuseppe, Santini, Daniele, and Recine, Federica
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THERAPEUTIC use of antineoplastic agents , *THERAPEUTIC use of antimetabolites , *NAUSEA , *VOMITING , *IRINOTECAN , *ANEMIA , *PATIENT safety , *TEMOZOLOMIDE , *MICRORNA , *TREATMENT effectiveness , *RANDOMIZED controlled trials , *TUMOR markers , *THROMBOCYTOPENIA , *NEUROENDOCRINE tumors , *FOLINIC acid , *RESEARCH , *GENE expression profiling , *QUALITY of life , *FLUOROURACIL , *PROGRESSION-free survival , *CONFIDENCE intervals , *OVERALL survival , *SEQUENCE analysis , *PATIENT aftercare , *NEUTROPENIA , *PLATINUM , *EVALUATION , *DISEASE risk factors ,RISK factors - Abstract
Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4–60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7–46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9–51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. NCT03387592 • No second-line treatment recognized for NEC patients after platinum-based therapy. • This phase II trial investigates activity and safety of second-line treatments in NEC. • FOLFIRI and CAPTEM in second-line setting improve the quality of life of NEC patients. • FOLFIRI or CAPTEM might be used interchangeably according ly to , comorbidities and toxicity profile. • miR-1246, miR-1290 and miR-320c are NEC independent prognostic predictors. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer.
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Yuan, Yuan, Lee, Jin Sun, Yost, Susan E., Stiller, Tracey, Blanchard, M. Suzette, Padam, Simran, Katheria, Vani, Kim, Heeyoung, Sun, Canlan, Tang, Aileen, Martinez, Norma, Patel, Niki Dipesh, Sedrak, Mina S., Waisman, James, Li, Daneng, Sanani, Shamel, Presant, Cary A., and Mortimer, Joanne
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The tolerability and efficacy of targeted therapy in older adults with cancer has not been adequately studied. Neratinib is a novel HER1, HER2, HER4 tyrosine kinase inhibitor that has recently been granted FDA approval for treatment of breast cancer. The major toxicity of neratinib is diarrhea, which affects up to 90% of patients. This phase II trial evaluates the safety and tolerability of neratinib in adults ≥60. Patients aged 60 or older with histologically proven metastatic breast cancer and HER2 amplification (defined by ASCO/CAP guideline) or HER2/HER3 activating mutation were enrolled to receive neratinib at 240 mg daily in 28-day cycles. The association between tolerability, defined as dose reduction and number of completed courses, and log 2 Cancer and Aging Research Group (CARG) toxicity risk score was assessed using a Student's t -test and linear regression, respectively. Response rate, progression free survival, and overall survival were also evaluated. 25 patients were enrolled with median age of 66 (range 60–79). Seventy-six percent of patients were white, 16% Asian, and 8% African-American. Seventy-six percent were patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and 24% were patients with HR negative MBC. Median number of prior lines of metastatic therapy were 3 (range 0–11). 20/25 (80%) had worst grade toxicities ≥2. A total of 9/25 (36%) had grade 3 toxicities including 5/20 (20%) diarrhea, 2/20 (8%) vomiting, and 2/20 (8%) abdominal pain. There were no grade 4 or 5 toxicities. A total of 9/25 (36%) had dose reduction, and 2/25 (8%) discontinued therapy due to toxicity. The association between dose reductions and CARG toxicity score reached borderline statistical significance suggesting a trend with participants with higher CARG toxicity risk scores being more likely to require a dose modification (p = 0.054). 1/25 (4%) had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not assessed. Median progression free survival (PFS) was 2.6 months (95% CI [2.56–5.26]), and median overall survival (OS) was 17.4 months (95% CI [10.3, NA]). Neratinib was safe in this population of older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer (BC). Higher CARG toxicity risk score may be associated with greater need for dose adjustments. Future studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery – 7-Year results of a phase II trial.
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Mészáros, Norbert, Major, Tibor, Stelczer, Gábor, Jánváry, Levente, Zaka, Zoltán, Pukancsik, Dávid, Takácsi-Nagy, Zoltán, Md, János Fodor, and Polgár, Csaba
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ACCELERATED partial breast irradiation ,LUMPECTOMY ,IMAGE-guided radiation therapy ,INTENSITY modulated radiotherapy ,INTERSTITIAL brachytherapy - Abstract
To present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS). Between 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3–5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed. At a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively. 7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI. • Phase II APBI trial using 3D-CRT or IG-IMRT. • Twice-a-day fractionation, with a total dose of 36.9 Gy (9 × 4.1Gy). • No Grade 2 or worst late side effects with IG-IMRT at median follow up of 90 months. • These APBI techniques are valid alternatives to WBI or brachytherapy based APBI. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16).
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Metaxas, Y., Früh, M., Eboulet, E.I., Grosso, F., Pless, M., Zucali, P.A., Ceresoli, G.L., Mark, M., Schneider, M., Maconi, A., Perrino, M., Biaggi-Rudolf, C., Froesch, P., Schmid, S., Waibel, C., Appenzeller, C., Rauch, D., and von Moos, R.
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MESOTHELIOMA , *IMMUNOTHERAPY , *CLINICAL trials , *CANCER treatment , *DRUG efficacy - Abstract
Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6–9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS 12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%). Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS 12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2–7.4). No significant difference in PFS 12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3–4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. NCT03213301 • Lurbinectedin demonstrated clinical activity in 42 patients with progressing MPM, with acceptable toxicity. • Analysis of histology, prior immunotherapy, time to progression on first-line chemotherapy revealed benefit in all subgroups. • Lurbinectedin emerges as a new treatment option and evaluation in a larger randomised trial is warranted. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Individualized accelerated isotoxic concurrent chemo-radiotherapy for stage III non-small cell lung cancer: 5-Year results of a prospective study.
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De Ruysscher, Dirk, van Baardwijk, Angela, Wanders, Rinus, Hendriks, Lizza E., Reymen, Bart, van Empt, Wouter, Öllers, Michel C., Bootsma, Gerben, Pitz, Cordula, van Eijsden, Linda, and Dingemans, Anne-Marie C.
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NON-small-cell lung carcinoma , *LONGITUDINAL method - Abstract
• With isotoxic radiotherapy dose escalation given concurrently with chemotherapy in patients with stage III NSCLC, toxicity was indeed as predicted and fairly low, but dose escalation could only be achieved in a minority of patients. • Local failure rates as well as the overall survival were similar to those reported with conventional radiotherapy. Stage III non-small cell lung cancer (NSCLC) still has a poor prognosis. Prior studies with individualized, accelerated, isotoxic dose escalation (INDAR) with 3D-CRT showed promising results, especially in patients not treated with concurrent chemo-radiotherapy. We investigated if INDAR delivered with IMRT would improve the overall survival (OS) of stage III NSCLC patients treated with concurrent chemotherapy and radiotherapy. Patients eligible for concurrent chemo-radiotherapy were entered in this prospective study. Radiotherapy was given to a dose of 45 Gy/30 fractions BID (1.5 Gy/fraction), followed by QD fractions of 2 Gy until a total dose determined by the normal tissue constraints. The primary endpoint was OS, secondary endpoints were loco-regional relapses and toxicity. From May 4, 2009 until April 26, 2012, 185 patients were included. The mean tumor dose was 66.0 ± 12.8 Gy (36–73 Gy), delivered in a mean of 39.7 fractions in an overall treatment time of 38.2 days. The mean lung dose (MLD) was 17.3 Gy. The median OS was 19.8 months (95% CI 17.3–22.3) with a 5-year OS of 24.3%. Loco-regional failures as first site of recurrence occurred in 59/185 patients (31.8%). Isolated nodal failures (INF) were observed in 3/185 patients (1.6%). Dyspnea grade 3 was seen in 3.2% of patients and transient dysphagia grade 3 in 22%. INDAR with IMRT concurrently with chemotherapy did not lead to a sign of an improved OS in unselected stage III NSCLC patients. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Organizing a clinical trial for the new investigator.
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Kukreja, Janet Baack, Thompson, Ian M., and Chapin, Brian F.
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CLINICAL trials , *NEW trials , *MENTORING - Abstract
Abstract Background and purpose Clinical trials organization can be daunting especially when orienting to a new system. The steps to a successful clinical trial are not concrete and vary based on the system. Methods In this section the discussion centers on how to shape the question for the clinical trial which is rational and feasible to answer within the planned study design. Findings Senior mentorship, collaboration and early involvement of stakeholders can help shape a successful clinical trial. Keeping in mind ethics and the processes within a system will make planning easier. Questions about key elements of the trial should be answered early to prevent delays of study initiation. Conclusion Clinical trial development and implementation can be very rewarding, but successful outcomes require careful planning and considerations. [ABSTRACT FROM AUTHOR]
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- 2019
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11. Adjuvant postoperative high-dose radiotherapy for atypical and malignant meningioma: A phase-II parallel non-randomized and observation study (EORTC 22042-26042).
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Pica, Alessia, Weber, Damien C., Lucas, Anna, Veninga, Theo, Jefferies, Sarah, Ricardi, Umberto, Stelmes, Jean-Jacques, Liu, Yan, Collette, Laurence, Collette, Sandra, Miralbell, Raymond, Ares, Carmen, Baumert, Brigitta G., Villa, Salvador, Peerdeman, Saskia M., and Renard, Laurette
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MENINGIOMA , *CLINICAL trials , *RADIOTHERAPY , *PROGRESSION-free survival , *DOSE-response relationship (Radiation) - Abstract
Purpose The therapeutic strategy for non-benign meningiomas is controversial. The objective of this study was to prospectively investigate the impact of high dose radiation therapy (RT) on the progression-free survival (PFS) rate at 3 years in WHO grade II and III meningioma patients. Materials and methods In this multi-cohorts non-randomized phase II and observational study, non-benign meningioma patients were treated according to their WHO grade and Simpson’s grade. Patients with atypical meningioma (WHO grade II) and Simpson’s grade 1–3 [Arm 1] entered the non-randomized phase II study designed to show a 3-year PFS > 70% (primary endpoint). All other patients entered the 3 observational cohorts: WHO grade II Simpson grade 4–5 [Arm 2] and Grade III Simpson grade 1–3 or 4–5 [Arm 3&4] in which few patients were expected. Results Between 02/2008 and 06/2013, 78 patients were enrolled into the study. This report focuses on the 56 (median age, 54 years) eligible patients with WHO grade II Simpson’s grade 1–3 meningioma who received RT (60 Gy). At a median follow up of 5.1 years, the estimated 3-year PFS is 88.7%, hence significantly greater than 70%. Eight (14.3%) treatment failures were observed. The 3-year overall survival was 98.2%. The rate of late signs and symptoms grade 3 or more was 14.3%. Conclusions These data show that 3-year PFS for WHO grade II meningioma patients undergoing a complete resection (Simpson I–III) is superior to 70% when treated with high-dose (60 Gy) RT. [ABSTRACT FROM AUTHOR]
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- 2018
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12. A randomized phase II study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive‐disease small cell lung cancer.
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Salgia, Ravi, Stille, John R., Weaver, R. Waide, McCleod, Michael, Hamid, Oday, Polzer, John, Roberson, Stephanie, Flynt, Amy, and Spigel, David R.
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CANCER treatment , *SMALL cell lung cancer , *COMBINATION drug therapy , *CARBOPLATIN , *ETOPOSIDE , *PATIENTS - Abstract
Objectives This multicenter, open-label, randomized phase II study evaluated the efficacy and safety of LY2510924 (LY) added to first‐line standard of care (SOC) chemotherapy for extensive-disease small cell lung cancer (ED-SCLC) and explored the predictive value of C‐X‐C motif receptor 4 (CXCR4) tumor response. Materials and methods Patients with treatment-naïve ED-SCLC were randomized (1:1) to receive up to six 21-day cycles of carboplatin/etoposide alone (SOC) or in combination with 20 mg LY2510924 administered subcutaneously on days 1–7 of each cycle (LY + SOC). The primary efficacy endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety. Response relative to CXCR4 expression on baseline tumor was an exploratory endpoint. Results Of 94 patients randomized, 90 received treatment (LY + SOC, n = 47; SOC, n = 43). Median PFS (95% confidence interval [CI]) was 5.88 (4.83, 6.24) months for LY + SOC versus 5.85 (4.63, 5.51) months for SOC (hazard ratio [95% CI], 1.01 [0.62, 1.63]; p = 0.9806). Median OS (95% CI) was 9.72 (6.64, 11.70) months for LY + SOC versus 11.14 (8.25, 13.44) months for SOC. ORR was 74.5% for LY + SOC versus 81% for SOC. Safety results between arms were similar, although the following adverse events were more frequent on the LY + SOC arm: anemia (61.7% vs 46.5%), neutropenia (61.7% vs 53.5%), leukopenia (27.7% vs 9.3%), vomiting (27.7% vs 16.3%), and pneumonia (10.6% vs 2.3%). In patients whose baseline CXCR4 expression was above the optimal cutoff (H‐score 210), the hazard ratio (95% CI) was 1.27 (0.51, 3.15). Conclusion LY2510924 did not improve efficacy but had an acceptable toxicity profile when added to SOC for ED‐SCLC. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Phase II trial of weekly nab-paclitaxel for previously treated advanced non–small cell lung cancer: Kumamoto thoracic oncology study group (KTOSG) trial 1301.
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Sakata, Shinya, Saeki, Sho, Okamoto, Isamu, Otsubo, Kohei, Komiya, Kazutoshi, Morinaga, Ryotaro, Yoneshima, Yasuto, Koga, Yuichiro, Enokizu, Aimi, Kishi, Hiroto, Hirosako, Susumu, Yamaguchi, Emi, Aragane, Naoko, Fujii, Shinji, Harada, Taishi, Iwama, Eiji, Semba, Hiroshi, Nakanishi, Yoichi, and Kohrogi, Hirotsugu
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PACLITAXEL , *CANCER treatment , *NON-small-cell lung carcinoma , *CANCER chemotherapy , *MEDICATION safety , *DRUG efficacy , *DISEASE progression , *CLINICAL trials - Abstract
Objectives We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC). Methods Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR). Results Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7% (90% confidence interval, 19.3%–44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4–7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0–18.0 months) months. The median number of treatment cycles was four (range, 1–17) over the entire study period, and the median dose intensity was 89.1 mg/m 2 per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%. Conclusion Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Is there still a role for sorafenib in metastatic renal cell carcinoma? A systematic review and meta-analysis of the effectiveness of sorafenib over other targeted agents.
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Iacovelli, Roberto, Verri, Elena, Cossu Rocca, Maria, Aurilio, Gaetano, Cullurà, Daniela, Santoni, Matteo, de Cobelli, Ottavio, and Nolé, Franco
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SORAFENIB , *METASTASIS , *RENAL cell carcinoma , *SYSTEMATIC reviews , *MEDICAL statistics - Abstract
Background The treatment of metastatic renal cell carcinoma (mRCC) has largely improved over the last decade, due to the availability of several targeted agents (TAs). Sorafenib was the first TA to report a benefit in terms of PFS in this disease, and it has largely been used as a comparator in randomized trials. We tested its activity compared to other TAs by performing a systematic review and meta-analysis. Methods MEDLINE/PubMed, the Cochrane library, and the ASCO university websites were searched for randomized phase II or III trials that compared other TAs to sorafenib in mRCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The measured outcomes were progression free survival (PFS), overall survival (OS), and the overall response rate (ORR). Sub-analyses were performed for MSKCC prognostic groups and lines of therapy. Results A total of 3094 patients were evaluable for PFS. Other TAs significantly reduce the risk of progression compared to sorafenib (HR = 0.78; 95% CI, 0.72–0.85; p < 0.001). This difference remains significant in patients in a good prognostic group with respect to both first- (HR = 0.61; 95%CI, 0.44–0.85; p = 0.003) and second-line therapy (HR = 0.58; 95% CI, 0.42–0.79; p < 0.001). No significant differences were, however, found in patients with an intermediate prognosis in terms of both first- (HR = 0.80; 95% CI, 0.60–1.00; p = 0.05) and second-line treatment (HR = 0.89; 95% CI, 0.73–1.07; p = 0.21). In 2922 patients evaluable for OS, no significant difference was found between other TAs and sorafenib (HR = 1.07; 95% CI, 0.97–1.18; p = 0.18). A benefit was also not identified when the analysis was limited to patients treated with first or subsequent lines of therapy or in patients previously treated with sunitinib. Significant differences were found in terms of the ORR in the 2963 evaluable patients favoring other TAs (RR = 1.48; 95% CI, 1.24–1.76; p < 0.001). This difference remain significant when a sub-analysis was performed per line of therapy. Conclusions Other TAs improve PFS but not OS when compared to sorafenib. The use of sorafenib in patients with an intermediate prognosis, especially in second-line therapy, does not have a detrimental effect on PFS and might be an option for certain patients. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO).
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Bompas, E., Le Cesne, A., Tresch-Bruneel, E., Lebellec, L., Laurence, V., Collard, O., Saada-Bouzid, E., Isambert, N., Blay, J. Y., Amela, E. Y., Salas, S., Chevreau, C., Bertucci, F., Italiano, A., Clisant, S., and Penel, N.
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CANCER chemotherapy , *CHORDOMA , *EPIDERMAL growth factor , *SACRUM , *RADIOTHERAPY , *THERAPEUTICS - Abstract
Background: There is no consensual treatment of locally advanced or metastatic chordomas. Patients and methods: We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. Results: Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30-86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1-88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8-96.5). Survival curves were similar in pretreated and not pretreated patients. Discussion: Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted. [ABSTRACT FROM AUTHOR]
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- 2015
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16. A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma.
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Gilbert, Jill, Schell, Michael J., Zhao, Xiuhua, Murphy, Barbara, Tanvetyanon, Tawee, Leon, Marino E., Neil Hayes, D., Jr.Haigentz, Missak, Saba, Nabil, Nieva, Jorge, Bishop, Justin, Sidransky, David, Ravi, Rajani, Bedi, Atul, and Chung, Christine H.
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CANCER treatment , *SQUAMOUS cell carcinoma , *CETUXIMAB , *RANDOMIZED controlled trials , *HEAD & neck cancer treatment , *DRUG efficacy , *CANCER relapse , *THERAPEUTICS - Abstract
Summary Introduction A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit. Material and Methods In a randomized phase II study, R/M HNSCC patients were treated with cetuximab 400 mg/m 2 IV on day 1 followed by 250 mg/m 2 IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400 mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p16 and HPV status, and plasma immunomodulatory cytokine levels were assessed. Results Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned treatments and 43 were evaluable for response. Overall response rate was 8% for both arms. Median overall survival (OS) and progression-free survival (PFS) were 9.0 and 3.0 months in Arm A, and 5.7 and 3.2 months in Arm B, respectively. Forty-four patients had tumors available for p16 staining (35-negative, 9-positive). Three of nine p16-positive tumors were also HPV positive. The p16-negative patients had significantly better PFS compared to the p16-positive patients (3.7 vs. 1.6 months; p -value: 0.03), regardless of study arms. Twenty-four plasma samples were tested for 12 cytokine levels and patients with higher TGFβ1 levels had inferior PFS compared to lower levels (1.9 vs. 4.7 months; adjusted p -value: 0.015), regardless of study arms. Conclusions A subset of R/M patients with p16-negative tumors or lower plasma TGFβ1 levels had longer PFS given the cetuximab-based therapy. However, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit. [ABSTRACT FROM AUTHOR]
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- 2015
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17. A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer.
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Zhao, Hanxi, Xie, Peng, Li, Xiaolin, Zhu, Wanqi, Sun, Xindong, Sun, Xiaorong, Chen, Xiaoting, Xing, Ligang, and Yu, Jinming
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EOSINOPHILIC esophagitis , *ESOPHAGUS diseases , *RADIOTHERAPY , *LUNG cancer prognosis , *CARCINOGENS , *THERAPEUTICS - Abstract
Background Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients’ quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440 μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly ( P = 0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline ( P = 0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment. [ABSTRACT FROM AUTHOR]
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- 2015
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18. A phase II study of cisplatin plus S-1 with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer: The Okayama Lung Cancer Study Group Trial 0501.
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Nogami, Naoyuki, Takigawa, Nagio, Hotta, Katsuyuki, Segawa, Yoshihiko, Kato, Yuka, Kozuki, Toshiyuki, Oze, Isao, Kishino, Daizo, Aoe, Keisuke, Ueoka, Hiroshi, Kuyama, Shoichi, Harita, Shingo, Okada, Toshiaki, Hosokawa, Shinobu, Inoue, Koji, Gemba, Kenichi, Shibayama, Takuo, Tabata, Masahiro, Takemoto, Mitsuhiro, and Kanazawa, Susumu
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CISPLATIN , *THORACIC surgery , *CANCER radiotherapy , *CANCER treatment , *NON-small-cell lung carcinoma , *HEALTH outcome assessment , *FLUOROURACIL derivatives , *CANCER patients - Abstract
Background Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective. Methods In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40 mg/m 2 on days 1, 8, 29 and 36) and S-1 (80 mg/m 2 on days 1–14 and 29–42) and TRT (60 Gy). The primary endpoint was the response rate. Results A partial response was observed in 37 patients (77%; 95% confidence interval: 63–88%). At a median follow up of 54 months, the median progression-free survival and median survival time were 9.3 and 31.3 months, respectively. No difference in efficacy was observed when the patients were stratified by histology. Toxicities were generally mild except for grade 3 or worse febrile neutropenia and pneumonitis of 8% and 4%, respectively. No patient developed severe esophagitis. At the time of this analysis, 35 (73%) of the 48 patients recurred; 15 (31%) showed distant metastasis, 17 (35%) had loco-regional disease, and 2 (4%) showed both loco-regional disease and distant metastasis. Conclusions This chemoradiotherapy regimen yielded a relatively favorable efficacy with mild toxicities in patients with locally advanced NSCLC. [ABSTRACT FROM AUTHOR]
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- 2015
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19. Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: A phase II randomised trial.
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Reni, Michele, Cereda, Stefano, Milella, Michele, Novarino, Anna, Passardi, Alessandro, Mambrini, Andrea, Di Lucca, Giuseppe, Aprile, Giuseppe, Belli, Carmen, Danova, Marco, Bergamo, Francesca, Franceschi, Enrico, Fugazza, Clara, Ceraulo, Domenica, and Villa, Eugenio
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CONFIDENCE intervals , *METASTASIS , *SCIENTIFIC observation , *HEALTH outcome assessment , *PANCREATIC tumors , *PHOSPHOTRANSFERASES , *PROBABILITY theory , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *CHEMICAL inhibitors , *EVALUATION - Abstract
Abstract: Background: New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Methods: Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6months (arm B). The primary outcome measure was the probability of being progression-free at 6months (PFS-6) from randomisation. Assuming P0=10%; P1=30%, α .10; β .10, the target accrual was 26 patients per arm. Results: 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91days (7–186). Main grade 3–4 toxicity was thrombocytopenia, neutropenia and hand–foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0–10.6%) and 22.2% (95% CI: 6.2–38.2%; P <0.01); 2y overall survival was 7.1% (95% CI: 0–16.8%) and 22.9% (95% CI: 5.8–40.0%; P =0.11), stable disease 21.4% and 51.9% (P =0.02). Conclusion: This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population. [Copyright &y& Elsevier]
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- 2013
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20. Optimal continuous-monitoring design of single-arm phase II trial based on the simulated annealing method.
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Chen, Nan and Lee, J. Jack
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CLINICAL trials , *PATIENT monitoring , *NULL hypothesis , *PROBABILITY theory , *SIMULATED annealing , *MATHEMATICAL optimization - Abstract
Abstract: Simon's two-stage design is commonly used in phase II single-arm clinical trials because of its simplicity and smaller sample size under the null hypothesis compared to the one-stage design. Some studies extend this design to accommodate more interim analyses (i.e., three-stage or four-stage designs). However, most of these studies, together with the original Simon's two-stage design, are based on the exhaustive search method, which is difficult to extend to high-dimensional, general multi-stage designs. In this study, we propose a simulated annealing (SA)-based design to optimize the early stopping boundaries and minimize the expected sample size for multi-stage or continuous monitoring single-arm trials. We compare the results of the SA method, the decision-theoretic method, the predictive probability method, and the posterior probability method. The SA method can reach the smallest expected sample sizes in all scenarios under the constraints of the same type I and type II errors. The expected sample sizes from the SA method are generally 10–20% smaller than those from the posterior probability method or the predictive probability method, and are slightly smaller than those from the decision-theoretic method in almost all scenarios. The SA method offers an excellent alternative in designing phase II trials with continuous monitoring. [Copyright &y& Elsevier]
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- 2013
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21. Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer
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Haigentz, Missak, Kim, Mimi, Sarta, Catherine, Lin, Juan, Keresztes, Roger S., Culliney, Bruce, Gaba, Anu G., Smith, Richard V., Shapiro, Geoffrey I., Chirieac, Lucian R., Mariadason, John M., Belbin, Thomas J., Greally, John M., Wright, John J., and Haddad, Robert I.
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SQUAMOUS cell carcinoma , *CANCER treatment , *HISTONE deacetylase inhibitors , *CLINICAL trials , *HEAD & neck cancer treatment , *CANCER relapse , *METASTASIS - Abstract
Summary: Objectives: Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors. Methods: A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13mg/m2 as a 4-h intravenous infusion on days 1, 8 and 15 of 28day cycles, with response assessment by RECIST every 8weeks. Results: Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21Waf1/Cip1 characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors. Conclusions: Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified. [ABSTRACT FROM AUTHOR]
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- 2012
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22. A multicenter phase II randomized trial of gemcitabine followed by erlotinib at progression, versus the reverse sequence, in vulnerable elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0505 study)
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LeCaer, H., Greillier, L., Corre, R., Jullian, H., Crequit, J., Falchero, L., Dujon, C., Berard, H., Vergnenegre, A., and Chouaid, C.
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RANDOMIZED controlled trials , *CANCER invasiveness , *OLDER patients , *CANCER treatment , *SMALL cell lung cancer , *GERIATRIC assessment , *CANCER chemotherapy - Abstract
Abstract: Background: The aim of this randomized phase II trial was to evaluate the feasibility and activity of weekly gemcitabine (G) followed by erlotinib at disease progression (arm A) versus erlotinib followed by G at progression (arm B) in vulnerable elderly patients with advanced non small-cell lung cancer (NSCLC), selected on the basis of a comprehensive geriatric assessment (CGA). Methods: Vulnerable elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a CGA (socioeconomic, cognitive and emotional status, depression, nutritional status, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), time to first progression (TTP1) and safety were secondary endpoints. Results: Between May 2006 and January 2010, 21 centers enrolled 100 patients, of whom 94 were eligible. TTP2 was 4.3 and 3.5 months in arm A and arm B, respectively; TTP1 was 2.5 and 2.2 months; and the median OS time was 4.4 and 3.9 months. The respective one-year survival rates were 27.3% and 20%. There was no major unexpected toxicity. Conclusion: In vulnerable elderly patients with NSCLC not selected for EGFR expression, both strategies were feasible but had modest efficacy. Further studies are needed to identify elderly patients who should receive palliative care only. [Copyright &y& Elsevier]
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- 2012
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23. Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: A phase II trial
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Kennecke, Hagen, Berry, Scott, Wong, Ralph, Zhou, Chen, Tankel, Keith, Easaw, Jacob, Rao, Sanjay, Post, Jacqueline, and Hay, John
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ANALYSIS of variance , *ANTINEOPLASTIC agents , *CLINICAL trials , *SURGICAL complications ,RECTUM tumors - Abstract
Abstract: Background: To evaluate the safety and efficacy of pre-operative chemoradiation, using capecitabine, oxaliplatin and bevacizumab with standard doses of radiation, in patients with high-risk rectal cancer. Methods: Patients with locally advanced or low rectal cancer were treated with capecitabine 825mg/m2 twice daily on days 1–14 and 22–35, oxaliplatin 50mg/m2 on days 1, 8, 22 and 29, bevacizumab 5mg/kg on days 14, 1, 15 and 29, and radiation 50.4Gy in 28 fractions including boost. Total mesorectal excision was performed 7–9weeks after chemoradiation. The primary end-point was complete tumour regression (ypT0NX) by central review. Findings: Forty-two evaluable patients were enrolled, and 38 proceeded to definitive surgery. Eighteen patients (43%) had clinical T4 tumours and/or N2 tumours. Mean relative dose intensity was >90% for all systemic agents, and 97% for radiation. Grade 3/4 diarrhoea occurred in 10 patients (24%) and pain in 4 patients (10%) pre-operatively, while grade 3/4 pain, fatigue and infection were each reported among 5 patients (13%) post-operatively. Re-operation due to complications occurred in 4 patients (11%). Complete tumour regression (ypT0) was seen in 9 patients (23.7%) of which two had N1 disease and the pathological complete response (pCR) rate (ypT0N0) was 18.4%. Central review changed pathologic stage in six cases (16%). Interpretation: In this study, pre-operative bevacizumab added to oxaliplatin, capecitabine and radiation was safe and resulted in a promising tumour regression rate. Surgical complications were closely monitored and occurred with the expected frequency. Central pathology review should be considered for trials with pathologic response as the primary end-point. Funding: British Columbia Cancer Agency, Hoffmann-La Roche Canada and Sanofi-Aventis. [Copyright &y& Elsevier]
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- 2012
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24. Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.
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Stupp, R., Tosoni, A., Bromberg, J. E. C., Hau, P., Campone, M., Gijtenbeek, J., Frenay, M., Breimer, L., Wiesinger, H., Allgeier, A., van den Bent, M. J., Bogdahn, U., van der Graaf, W., Yun, H. J., Gorlia, T., Lacombe, D., and Brandes, A. A.
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GLIOMAS , *CANCER chemotherapy , *DISEASE progression , *PHARMACOKINETICS , *BLOOD plasma , *NEUROPATHY , *ONCOLOGY - Abstract
Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood–brain barrier has demonstrated preclinical activity in glioma models.Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points.Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3–18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3–12.3), with a 1-year survival rate of 31.6% (95% CI 17.7–46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination.Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration. [ABSTRACT FROM AUTHOR]
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- 2011
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25. Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer.
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Zweifel, M., Jayson, G. C., Reed, N. S., Osborne, R., Hassan, B., Ledermann, J., Shreeves, G., Poupard, L., Lu, S.-P., Balkissoon, J., Chaplin, D. J., and Rustin, G. J. S.
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OVARIAN cancer , *PHOSPHATES , *PACLITAXEL , *NEUTROPENIA , *THROMBOCYTOPENIA , *NEUROPATHY , *NITROGLYCERIN - Abstract
Background: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer.Patients and methods: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m2 minimum 18 h before paclitaxel 175 mg/m2 and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks.Results: Five of the first 18 patients’ disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%.Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis. [ABSTRACT FROM AUTHOR]
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- 2011
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26. Phase II trial of amrubicin and carboplatin in patients with sensitive or refractory relapsed small-cell lung cancer
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Hirose, Takashi, Nakashima, Masanao, Shirai, Takao, Kusumoto, Sojiro, Sugiyama, Tomohide, Yamaoka, Toshimitsu, Okuda, Kentaro, Ohnishi, Tsukasa, Ohmori, Tohru, and Adachi, Mitsuru
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LUNG cancer treatment , *ANTINEOPLASTIC agents , *ANTHRACYCLINES , *CANCER relapse , *CLINICAL trials , *XENOGRAFTS - Abstract
Abstract: Amrubicin is a novel, totally synthesized anthracycline derivative, and has antitumor activity against several human tumor xenografts. The combination of amrubicin with platinum derivative showed additive effect against a human small-cell lung cancer (SCLC) cell line. Until now, the combination of amrubicin plus carboplatin has not been studied in patients with previously treated SCLC. Therefore, we examined the safety and efficacy of the combination of amrubicin plus carboplatin in patients with sensitive or refractory relapsed SCLC. Patients with previously treated SCLC were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. Twenty-five patients were enrolled (21 men and 4 women; median age, 65 years; age range 55–73 years). Patients received the combination of amrubicin (30mg/m2 on days 1–3) plus carboplatin (with a target area under the concentration-versus-time curve of 4mgmin/ml using the Calvert formula on day 1) every 3 weeks. The overall response rate was 36.0% (95% confidence interval [CI], 18.0–57.5%). Response rates differed significantly between patients with sensitive relapse (58.3%; 95% CI, 27.7–84.8%) and those with refractory relapse (15.4%; 95% CI, 1.9–15.4%; p =0.03). The median survival time (MST) from the start of this treatment was 7 months (range: 1–42 months); the MST of patients with sensitive relapse (10 months) was significantly longer than that of patients with refractory relapse (5 months: p =0.004). The median progression-free survival (PFS) time was 3 months (range: 1–14 months): the median PFS time of patients with sensitive relapse (5 months) was significantly longer than that of patients with refractory relapse (2 months; p =0.01). The most frequent grade 3–4 toxicity was myelosuppression, especially neutropenia, which developed in 88% of patients. Grade 3–4 thrombocytopenia developed in 44% of patients, and anemia developed in 56%. Nonhematologic toxicities were generally mild to moderately severe and temporary. None of the patients had cardiotoxicity. In conclusion, this therapy is effective and well tolerated for previously treated SCLC. [Copyright &y& Elsevier]
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- 2011
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27. Phase II trial of paclitaxel and uracil–tegafur in metastatic breast cancer. TEGATAX trial.
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Villanueva, C., Chaigneau, L., Dufresne, A., Thierry Vuillemin, A., Stein, U., Demarchi, M., Bazan, F., N’Guyen, T., and Pivot, X.
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CLINICAL trials ,PACLITAXEL ,URACIL ,METASTASIS ,BREAST cancer treatment ,DRUG therapy ,ANTHRACYCLINES ,DRUG dosage ,DISEASE progression - Abstract
Abstract: This Phase II trial investigated the combination paclitaxel (P) and uracil–tegafur (UFT) in patients with metastatic breast cancer (MBC). Methods: Main eligibility criteria included HER-2 negative MBC, ECOG performance status of 0–2, exposure to 1–2 prior chemotherapy regimen in the metastatic setting, previous exposure to an anthracycline containing regimen either at metastatic or adjuvant setting. Each 35-day cycle consisted of P at 80 mg/m
2 by intravenous infusion on days 1, 8, 15, 22 and 29 and oral UFT at 300 mg/m2 TID (three time a day) from days 1–28 and oral folinic acid at 90 mg QD (one a day). Results: Between March 2003 and December 2007, 31 patients were enrolled. Median age was 66 years (range 44–78). All tumours were HER-2 negative and 7% were triple negative (ER, PgR, HER-2). The majority of patients had visceral disease (81%). All patients had received an anthracycline containing regimen and 74% had a previous docetaxel containing treatment. Median of 4 and 3 cycles of P and UFT were administered with a relative dose intensity of 85.3% and 94.3%, respectively. Twelve (40%)(95% CI: 22.5–57.5) confirmed ORR were observed. Stable and progression disease were reported in 43% and 17% of cases. Median Response duration was 8.4 month (95% CI: 4.9–11.7), median Time to progression was 9.5 months (95% CI: 6.6–13.8) and median Overall Survival was 23.5 months (95% CI: 16.8–37.2). Thirteen pts (43%) experienced a grade 3 or 4 adverse events (AEs): One death occurred related to the study drugs (febrile neutropenia). Chemotherapy was discontinued due to toxicity in 30% of pts Conclusions: Accrual was closed in January 2008 due to concerns regarding the degree and accumulative nature of AEs. Nonetheless, the ORR is encouraging and warranted further studies with adapted doses and schedules. [Copyright &y& Elsevier]- Published
- 2011
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28. Phase II study of S-1, an oral fluoropyrimidine, in patients with advanced or recurrent cervical cancer.
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Katsumata, N., Hirai, Y., Kamiura, S., Sugiyama, T., Kokawa, K., Hatae, M., Nishimura, R., and Ochiai, K.
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FLUOROPYRIMIDINES , *CLINICAL trials , *CERVICAL cancer treatment , *CERVICAL cancer patients , *DRUG efficacy , *CANCER chemotherapy , *FOLLOW-up studies (Medicine) - Abstract
Background: S-1 is an oral fluoropyrimidine. This phase II study was designed to evaluate the efficacy and safety of S-1 in patients with advanced or recurrent uterine cervical cancer.Patients and methods: S-1 35 mg/m2 was given twice daily for 28 days repeated every 6 weeks. Eligible patients were women aged 20–74 years, who had Eastern Cooperative Oncology Group performance status of zero or one, who had stage IVB or recurrent uterine cervical cancer, and who had received no more than one platinum-containing chemotherapy regimen for stage IVB or recurrent disease. The primary end point was overall response rate (ORR) determined by RECIST.Results: A total of 37 patients were enrolled in the trial and 36 were eligible. The median number of cycles administered was 4. The confirmed ORR was 30.6% (95% confidence interval 15.5% to 45.6%). The response rate for patients who had received platinum-based treatment including chemoradiotherapy was 31.8% (7 of 22). After a median follow-up duration of 25 months, the median time to progression and the median survival time were 5.2 and 15.4 months, respectively. The most frequent grade 3 or 4 adverse events were anemia (16%), anorexia (16%), and diarrhea (22%).Conclusions: This phase II study of S-1 in cervical cancer suggests a promising response rate and a contribution toward prolonging survival, with modest toxic effects. Phase III studies of S-1 in patients with advanced or recurrent cervical cancer are thus warranted. [ABSTRACT FROM AUTHOR]
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- 2011
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29. Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up.
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Penel, N., Le Cesne, A., Bui, B. N., Perol, D., Brain, E. G., Ray-Coquard, I., Guillemet, C., Chevreau, C., Cupissol, D., Chabaud, S., Jimenez, M., Duffaud, F., Piperno-Neumann, S., Mignot, L., and Blay, J.-Y.
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CANCER treatment , *IMATINIB , *CLINICAL trials , *CANCER invasiveness , *CANCER relapse , *FOLLOW-up studies (Medicine) , *DRUG efficacy - Abstract
Background: Imatinib evaluated as a new treatment option in patients with recurrent or established progressive aggressive fibromatosis/desmoid tumor (AF/DT).Patients and methods: Forty patients with unresectable and progressive symptomatic AF/DT were treated with imatinib (400 mg/day for 1 year) in a Simon's optimal two-stage phase II study (P0 = 10%, P1 = 30%, α = 5%, β = 10%). The primary end point was non-progressive at 3 months (RECIST).Results: The study population consisted of 28 women and 12 men, with a mean age of 41 (range 20–72 years). Most of the primary sites were extra-abdominal (24, 54.5%). Familial adenomatous polyposis was observed in six (15%) cases. The median follow-up was 34 months. Imatinib toxicity was similar to that previously reported in literature. Tumor assessment was validated by a central independent radiology committee for 35 patients At 3 months, one (3%) complete and three (9%) partial confirmed responses were observed. The non-progression rates at 3, 6 and 12 months were, respectively, 91%, 80% and 67%. The 2-year progression-free and overall survival rates were 55% and 95%, respectively. Two patients with mesenteric AF/DT died from progressive disease.Conclusion: Imatinib is active in the treatment of recurrent and progressive AF/DT, providing objective response and long-term stable disease in a large proportion of patients. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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30. Clinical development of dietary supplements: The perils of starting at phase III
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Berman, Josh
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DIETARY supplement laws , *PLACEBOS , *ALTERNATIVE medicine , *CLINICAL trials , *DIETARY supplements , *DOSAGE forms of drugs , *DOSE-effect relationship in pharmacology , *MEDICINAL plants , *OMEGA-3 fatty acids , *POLYPHENOLS , *SAW palmetto , *UBIQUINONES , *DRUG development , *PLANT extracts , *PUBLICATION bias - Abstract
Abstract: Dietary supplements are in worldwide use particularly for diseases for which conventional agents are ineffective. Many of the diseases have subjective endpoints and variable natural histories which lead to large placebo effects. Phase III studies with their large resource requirements should not be undertaken until the commonly used dose of the dietary supplement has been evaluated vs placebo, and if necessary raised until specific efficacy is demonstrated, in phase II testing. If phase II tests precede phase III evaluation, a product destined to fail will not consume important resources, and the optimum dose of products destined to succeed can be identified. [Copyright &y& Elsevier]
- Published
- 2011
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31. The Deliverability, Acceptability, and Perceived Effect of the Macmillan Approach to Weight Loss and Eating Difficulties: A Phase II, Cluster-Randomized, Exploratory Trial of a Psychosocial Intervention for Weight- and Eating-Related Distress in People with Advanced Cancer
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Hopkinson, Jane B., Fenlon, Debbie R., Okamoto, Ikumi, Wright, David N.M., Scott, Issy, Addington-Hall, Julia M., and Foster, Claire
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WEIGHT loss , *EATING disorders , *SYMPTOMS , *APPETITE loss , *QUALITATIVE research , *QUANTITATIVE research , *MIXED methods research , *CANCER patients - Abstract
Abstract: Context: Up to 80% of people with cancer will develop weight loss and anorexia during the advanced stages of the disease. The Macmillan Weight and Eating Studies (2000–2009) have used the Medical Research Council complex interventions framework to develop the first psychosocial intervention for weight- and eating-related distress (WRD and ERD) in people with advanced cancer and their carers: The Macmillan Approach to Weight and Eating (MAWE). Objectives: This article reports the findings of a Phase II trial of MAWE that investigated its deliverability, acceptability, and patient-perceived effect on WRD and ERD. Methods: The Phase II trial, conducted in 2006–2007, was of cluster-randomized design, with two community palliative care teams randomized to different arms. It used mixed methods to compare an intervention group (n =25), the MAWE group, which was supported by MAWE-trained clinical nurse specialists, with a group that received usual care (n =25), the control group. Results: MAWE was deliverable in clinical practice and acceptable to patients. Unplanned exposure of the MAWE group to the intervention before an initial measure of WRD and ERD proved problematic to the trial process. Despite this, quantitative and qualitative analyses indicate that MAWE does not exacerbate WRD and ERD and may help patients with advanced cancer live with the weight loss and anorexia that are the symptoms of cancer cachexia syndrome. Conclusion: A follow-on randomized controlled trial of MAWE is warranted but should be of a revised design. [ABSTRACT FROM AUTHOR]
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- 2010
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32. A multicentre Phase II study of non-pegylated liposomal doxorubicin in combination with trastuzumab and docetaxel as first-line therapy in metastatic breast cancer.
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Venturini, M., Bighin, C., Puglisi, F., Olmeo, N., Aitini, E., Colucci, G., Garrone, O., Paccagnella, A., Marini, G., Crinò, L., Mansutti, M., Baconnet, B., Barbato, A., and Del Mastro, L.
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BREAST cancer treatment ,DOXORUBICIN ,METASTASIS ,TRASTUZUMAB ,DOCETAXEL ,DRUG toxicity ,EPIDERMAL growth factor ,CANCER chemotherapy - Abstract
Abstract: To evaluate the cardiotoxicity, general toxicity, and activity of non-pegylated liposomal doxorubicin, in combination with docetaxel and trastuzumab, as first-line therapy in metastatic breast cancer. Thirty-one patients with metastatic human epidermal growth factor receptor 2-overexpressing breast cancer, who had not previously received chemotherapy for metastatic disease, received non-pegylated liposomal doxorubicin (50mg/m
2 ), docetaxel (75mg/m2 ) and trastuzumab (2mg/kg/week) for up to eight cycles, followed by trastuzumab alone for up to 52 weeks. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) to below 45%, or a decrease in LVEF of at least 20% from baseline. Mean LVEF was maintained at baseline level also in the subset of patients who had received anthracycline previously. Cardiotoxicity developed in three patients during the treatment cycles, and in two further patients after the end of the study. The most common adverse events were haematological toxicity, alopecia, asthenia and fever. The best overall response rate was 65.5%. Median time to progression was 13.0 months. The combination of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab combines acceptable cardiac and general toxicity and promising activity as first-line therapy in metastatic breast cancer. [ABSTRACT FROM AUTHOR]- Published
- 2010
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33. Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)
- Author
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Schöffski, Patrick, Blay, Jean-Yves, De Greve, Jacques, Brain, Etienne, Machiels, Jean-Pascal, Soria, Jean-Charles, Sleijfer, Stefan, Wolter, Pascal, Ray-Coquard, Isabelle, Fontaine, Christel, Munzert, Gerd, Fritsch, Holger, Hanft, Gertraud, Aerts, Claire, Rapion, Jérome, Allgeier, Anouk, Bogaerts, Jan, and Lacombe, Denis
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ANTINEOPLASTIC agents , *CLINICAL drug trials , *PHARMACOKINETICS , *DRUG efficacy , *CLINICAL trials , *CANCER treatment , *BREAST tumor treatment , *MELANOMA treatment , *SARCOMA , *TUMOR treatment , *OVARIAN tumors , *CANCER patients , *CELL physiology , *MEDICAL care , *MEDICAL protocols , *MEDICAL societies , *PATIENTS , *DATA analysis , *PHOSPHOTRANSFERASES , *PATIENT selection , *DRUG administration , *DRUG dosage , *DRUG side effects , *EVALUATION , *THERAPEUTICS - Abstract
Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were ⩾18years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4weeks ago. BI 2536 200–250mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3–4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14–15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. [Copyright &y& Elsevier]
- Published
- 2010
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34. Gemcitabine and capecitabine in previously anthracycline-treated metastatic breast cancer: a multicenter phase II study (SOLTI 0301 trial).
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Ciruelos, E. M., Cortés, J., Cortés-Funes, H., Mayordomo, J. I., Bermejo, B., Ojeda, B., García, E., Rodríguez, C. A., Muñoz, M., Gómez, P., Manso, L., Andrés, R., Lluch, A., Saura, C., Mendiola, C., and Baselga, J.
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ANTHRACYCLINES , *DRUG efficacy , *BREAST cancer treatment , *CANCER patients , *FEBRILE neutropenia , *THERAPEUTICS - Abstract
Background: On the basis of clinical activity of capecitabine and gemcitabine for metastatic breast cancer, we carried out a multicenter phase II clinical trial on the combination of these two agents in advanced anthracycline-pretreated breast cancer patients. Main objectives were to assess its efficacy and safety profile. [ABSTRACT FROM PUBLISHER]
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- 2010
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35. A phase II study of amrubicin, a synthetic 9-aminoanthracycline, in patients with previously treated lung cancer
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Kaira, Kyoichi, Sunaga, Noriaki, Tomizawa, Yoshio, Yanagitani, Noriko, Shimizu, Kimihiro, Imai, Hisao, Utsugi, Mitsuyoshi, Iwasaki, Yasuki, Iijima, Hironobu, Tsurumaki, Hiroaki, Yoshii, Akihiro, Fueki, Naoto, Hisada, Takeshi, Ishizuka, Tamotsu, Saito, Ryusei, and Mori, Masatomo
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ANTINEOPLASTIC agents , *LUNG cancer treatment , *DRUG efficacy , *NEUTROPENIA , *DOSE-response relationship in biochemistry , *CLINICAL trials - Abstract
Abstract: Purpose: This study was designed to confirm the efficacy and safety of amrubicin, a new anthracycline agent, in patients with previously treated non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Methods: Eligible patients were required to have recurrent or refractory NSCLC and SCLC after one or two previous chemotherapy regimens. All patients received intravenous amrubicin 35mg/m2 on days 1–3 every 3 weeks. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Sixty-six patients (37 NSCLC and 29 SCLC) were assessable for efficacy and safety evaluation. Grade 3 or 4 neutropenia was observed in 39.4% of all patients (NSCLC, 37.8%; SCLC, 41.4%). Nonhematological toxicities were mild. No treatment-related death was observed. The ORRs were 13.5% (95% CI, 4.5–28.8%) in NSCLC and 44.8% (95% CI, 26.4–64.3%) in SCLC. In SCLC, ORRs were 60.0% in the sensitive relapse and 36.8% in the refractory relapse (p =0.2332). In NSCLC, the PFS, OS, and 1-year survival were 3.3 months, 12.0 months, and 35.3%, respectively. In SCLC, the PFS, OS, and 1-year survival were 4.0 months, 12.0 months, and 46.7%, respectively. Conclusions: Amrubicin is an active and well-tolerated regimen in patients with previously treated lung cancer. Amrubicin 35mg/m2 seems to achieve similar efficacy with less toxicity than amrubicin 40mg/m2 in this patient population. These results warrant further evaluation in previously treated lung cancer. [Copyright &y& Elsevier]
- Published
- 2010
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36. Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) Protocol.
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Meschia, James F., McNeil, Rebecca B., Barrett, Kevin M., Brott, Thomas G., Graff-Radford, Neill R., and Brown, Robert D.
- Abstract
Background: Stroke is the leading cause of acquired disability in adulthood. Ischemic stroke often results in physical, emotional, and cognitive impairment. There is no definitively proven pharmacologic technique to accelerate recovery from stroke. The short-term goal of this study is to develop donepezil hydrochloride as pharmacotherapy for enhancing stroke recovery. Design: The Mayo Acute Stroke Trial for Enhancing Recovery (MASTER) is a prospective, stratified 2-stage trial of donepezil for acute ischemic stroke. Suitable patients must receive treatment within 24 hours of developing symptoms. A total of 30 to 40 patients will be enrolled. Trial Procedures: Participants will receive up to 10 mg of donepezil daily for 90 days. Patients will be assessed at less than 24 hours (pretreatment), 30 days, 60 days, 90 days, and 6 months off-drug poststroke. Assessments will include examinations of neurologic, cognitive, functional, and psychological status. The primary outcome will be excellent neurologic recovery, defined as National Institutes of Health Stroke Scale score of 0 or 1 at 90 days after stroke. Secondary outcome measures are the proportion of patients with favorable outcomes defined as follows: National Institutes of Health Stroke Scale score of 0 or 1 at 6 months; modified Rankin scale score of 0 or 1 at 90 days and 6 months; modified Rankin scale score less than 3 at 90 days and 6 months; and Mini-Mental State Examination score greater than 24 at 90 days and 6 months. Trial Registration: Clinicaltrials.gov identifier NCT00805792. [Copyright &y& Elsevier]
- Published
- 2010
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37. Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer.
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Green, M. D., Francis, P. A., Gebski, V., Harvey, V., Karapetis, C., Chan, A., Snyder, R., Fong, A., Basser, R., and Forbes, J. F.
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BREAST cancer , *EPIDERMAL growth factor , *TUMORS , *CANCER treatment , *TAMOXIFEN - Abstract
Background: Acquired and de novo endocrine resistance in breast cancer (BC) may be associated with overexpression of epidermal growth factor receptor (EGFR). Gefinitib is an orally active selective EGFR inhibitor which might benefit advanced breast cancer (ABC) patients either with acquired hormone resistance or with hormone receptor (HR)-negative tumors. [ABSTRACT FROM PUBLISHER]
- Published
- 2009
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38. Pemetrexed in combination with oxaliplatin as a first-line therapy for advanced gastric cancer: a multi-institutional phase II study.
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Celio, L., Sternberg, C. N., Labianca, R., Torre, I. La, Amoroso, V., Barone, C., Pinotti, G., Cascinu, S., Costanzo, F. Di, Cetto, G. L., and Bajetta, E.
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STOMACH cancer , *CLINICAL trials , *OXALIPLATIN , *PATIENTS , *CANCER - Abstract
Background: This clinical trial assessed the efficacy of pemetrexed combined with oxaliplatin (PEMOX) in patients with advanced gastric cancer (AGC). [ABSTRACT FROM PUBLISHER]
- Published
- 2009
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39. A novel diagram and complement to the CONSORT chart for presenting multimodal clinical trials
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Schuller, Jan C., Mayer, Michael, Lanz, Doris, Schmitz, Shu-Fang Hsu, Brauchli, Peter, and Leupin, Nicolas
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CLINICAL medicine , *MEDICAL research , *MEDICAL experimentation on humans , *CLINICAL trials - Abstract
Abstract: We developed a novel diagram to depict patient flow and outcomes in clinical trials. In contrast to flow diagrams such as the CONSORT chart, our diagram enables individual patient histories to be traced and depicts important patterns of treatment administration and outcomes, such as response and adverse events. Also, it is particularly useful for multimodal treatments or a sequence of different therapies where the CONSORT flow chart is less informative and can be confusing. [Copyright &y& Elsevier]
- Published
- 2009
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40. Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia
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Frakking, Florine N.J., Brouwer, Nannette, van de Wetering, Marianne D., Budde, Ilona Kleine, Strengers, Paul F.W., Huitema, Alwin D., Laursen, Inga, Houen, Gunnar, Caron, Huib N., Dolman, Koert M., and Kuijpers, Taco W.
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PHARMACOKINETICS , *LECTINS , *BLOOD plasma , *NEUTROPENIA , *CHILDHOOD cancer , *CANCER chemotherapy , *BODY weight , *PATIENTS , *THERAPEUTICS - Abstract
Abstract: Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0–12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1–4 weeks). Four patients participated multiple times. Target levels of 1.0μg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06μg/ml (range: 0.66–2.05μg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25kg, was 36.4h (range: 23.7–66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective. [Copyright &y& Elsevier]
- Published
- 2009
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41. An open multicenter phase II trial of docetaxel–gemcitabine in Charlson score and performance status (PS) selected elderly patients with stage IIIB pleura/IV non-small-cell lung cancer (NSCLC): The GFPC 02-02a study
- Author
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LeCaer, H., Fournel, P., Jullian, H., Chouaid, C., LeTreut, J., Thomas, P., Paillotin, D., Perol, M., Gimenez, C., and Vergnenegre, A.
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LUNG cancer , *OLDER people , *COMORBIDITY , *DRUG therapy - Abstract
Abstract: The aim of this study was to determine the impact of patient selection based on age, comorbidity and performance status on the efficacy of platinum-free combination therapy on non-small-cell lung cancer after 65 years of age. We analyzed the overall response rate, the median survival time, the 1-year survival rate, toxicity and quality of life after one to three 6-week cycles of docetaxel 30mg/m2 weekly and gemcitabine 900mg/m2 at weeks 1, 2, 4 and 5. Fifty patients (median age 73.7 years) were eligible. The mean number of comorbid conditions per patient was 0.8 [Balducci L. Lung cancer and aging. ASCO 2005. Educational book. p. 587–91; Piquet J, Blanchon F, Grivaux M, et al. Primary bronchial carcinoma in elderly subjects in France. Rev Mal Respir 2003;20:691–9; Jatoi A, Hillman S, Stella P, et al. Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 2005;23:9113–9; Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000;5:224–37]. Forty-five patients were assessable: 17 (34%) had an objective response, 18 (36%) had stable disease and 10 progressed (20%). The median survival time was 7 months and the 1-year survival rate 23.5%. The main grade III–IV adverse event was neutropenia (32% of patients). Conclusion: Platinum-free dual-agent chemotherapy gives similar results in patients over 65, selected on the basis of their precise age and comorbidity, to that reported in younger subjects. [Copyright &y& Elsevier]
- Published
- 2007
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42. An open multicenter phase II trial of weekly docetaxel for advanced-stage non-small-cell lung cancer in elderly patients with significant comorbidity and/or poor performance status: The GFPC 02-02b study
- Author
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LeCaer, Hervé, Barlesi, Fabrice, Robinet, Gilles, Fournel, Pierre, Geriniere, Laurence, Bombaron, Pierre, Falchero, Lionel, Auliac, Jean Baptiste, Crequit, Jacky, and Chouaid, Christos
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CANCER patients , *ANTINEOPLASTIC agents , *DISEASES in older people , *LUNG cancer - Abstract
Summary: Context: The objective of this study was to evaluate the feasibility and activity of weekly docetaxel monotherapy in frail elderly patients with advanced-stage non-small-cell lung cancer, selected on the basis of their precise age, general condition, and number of comorbid disorders (Charlson score). Methods: Analysis of the response rate, toxicity, quality of life, median survival and 1-year survival rates after 1–3 six-week cycles of docetaxel 30mg/m2 weekly. Results: Fifty patients were enrolled and 42 were assessable. Five patients (10%, [3.7–22.6]) had objective responses, 14 (28%, [16.9–41.6]) had stable disease, and 23 (46%, [32.6–52.8]) progressed. The main grade 3–4 toxicity was fatigue (30%). Quality of life remained stable during treatment. The median survival time was 4.3 months, and the 1-year survival rate was 21.8%. Conclusion: In frail elderly patients selected on the basis of their age, general condition and comorbidity, weekly docetaxel monotherapy has acceptable toxicity and does not negatively affect quality of life. In contrast, it has only moderate activity. [Copyright &y& Elsevier]
- Published
- 2007
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43. Bi-weekly administration of gemcitabine plus vinorelbine in elderly patients with advanced non-small-cell lung cancer: Multicenter phase II trial
- Author
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Araya, Tomoyuki, Kasahara, Kazuo, Kimura, Hideharu, Shibata, Kazuhiko, Kita, Toshiyuki, Shirasaki, Hiroki, Hara, Johsuke, Yoshimi, Yuzo, Sone, Takashi, Oribe, Yoshitaka, Nobata, Kouichi, Nishi, Kouichi, Fujimura, Masaki, and Nakao, Shinji
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CANCER patients , *CANCER treatment , *PATIENTS , *DRUG therapy - Abstract
Summary: Purpose: Gemcitabine (GEM) and vinorelbine (VNR) have demonstrated activity as a first-line treatment in elderly patients with advanced non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial to evaluate the efficacy and toxicity of bi-weekly administration of GEM plus VNR in elderly patients with advanced NSCLC. Patients and methods: Forty-six chemotherapy-naive elderly (age: ≥70 years) NSCLC patients were enrolled. Patients were eligible if they had histologically or cytologically confirmed unresectable NSCLC with measurable and/or assessable disease. Patients received GEM (1000mg/m2) and VNR (25mg/m2) every 2 weeks. Results: The objective response rate of this treatment was 22.7% (95% confidence interval (CI), 10.3–35.1%), median survival time was 310 days, and median time to progression was 133 days. The one-year survival rate was 40.9% (95% CI, 26.3–55.4%), and most adverse events were mild. Only three (6.8%) patients needed to omit GEM because of grade 4 neutropenia or due to physician judgment. No patients suffered treatment-related death. Conclusions: Bi-weekly administration of GEM plus VNR in elderly patients was an effective, feasible and well-tolerated treatment schedule. [Copyright &y& Elsevier]
- Published
- 2007
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44. Brostallicin, an agent with potential activity in metastatic soft tissue sarcoma: A phase II study from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group
- Author
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Leahy, Michael, Ray-Coquard, Isabelle, Verweij, Jaap, Le Cesne, Axel, Duffaud, Florence, Hogendoorn, Pancras C.W., Fowst, Camilla, de Balincourt, Christine, di Paola, Eugenio Donato, van Glabbeke, Martine, Judson, Ian, and Blay, Jean-Yves
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MEDICAL research , *CANCER treatment , *SOFT tissue tumors , *GRANULOCYTOPENIA - Abstract
Abstract: The study aimed to assess the efficacy and safety of brostallicin, a new DNA minor groove binder, at a dose of 10mg/m2, intravenous (i.v.) every three weeks, in patients with advanced or inoperable soft tissue sarcoma (STS) and gastrointestinal stromal tumour (GIST) failing first line therapy. Two groups were recruited: (1) GIST following treatment with imatinib; (2) other STS following treatment with single agent doxorubicin or ifosfamide or a single line of combination therapy. The primary end-point was overall response rate (ORR) as defined by response evaluation criteria in solid tumours (RECIST). Progression free survival (PFS) was a secondary end-point. In the GIST group, a Simon two step design was planned: first step 18 patients, total 32 patients (p1=20% p0=5% alpha=beta=0.1). In the non-GIST group, planned sample size was 40 in a standard Fleming one-step design (p0=10%, p1=25%, alpha=beta=0.1). Forty-three patients with non-GIST and 21 patients with GIST were recruited. In general, the drug was well tolerated. Common Toxicity Criteria (CTC) grade 3 or grade 4 toxicity was granulocytopenia: 70% of patients, 50% of cycles; fatigue: 25% of patients, 8% of cycles; febrile neutropenia: 14% of patients, 4% of cycles. There was one confirmed toxic death due to neutropenic septicaemia. Three patients had clinically significant allergic reactions in 249 cycles delivered. In the GIST group, no patients had a confirmed response and recruitment was discontinued at the first step. In the non-GIST group, there were two confirmed partial responses. The 3 month PFS was 46% in the non-GIST group and 33% in the GIST group. In the non-GIST group, this PFS is in the range of other agents considered active in STS, and may predict for more substantial first line activity. Further investigation in STS other than GIST appears warranted. [Copyright &y& Elsevier]
- Published
- 2007
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45. Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer
- Author
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Trodella, L., De Marinis, F., D’Angelillo, R.M., Ramella, S., Cesario, A., Valente, S., Nelli, F., Migliorino, M.R., Margaritora, S., Corbo, G.M., Porziella, V., Ciresa, M., Cellini, F., Bonassi, S., Russo, P., Cortesi, E., and Granone, P.
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PHARMACOLOGY , *ANTINEOPLASTIC agents , *MEDICAL electronics , *MEDICAL radiology - Abstract
Summary: Background: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. Patients and Methods: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50mg/m2, paclitaxel 125mg/m2 and gemcitabine 1000mg/m2 on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250mg/m2). Toxicity and response of radio-chemotherapy treatment have been assessed. Results: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. Conclusion: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe. [Copyright &y& Elsevier]
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- 2006
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46. Phase II study of capecitabine single-agent therapy in patients with metastatic renal cell carcinoma
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Pagliaro, Lance C., Perez, Cherie A., Tu, Shi-Ming, and Daliani, Danai D.
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RENAL cell carcinoma , *THERAPEUTICS , *CLINICAL trials , *ANTIVIRAL agents - Abstract
Abstract: Fluoropyrimidines are known to have modest activity in the treatment of metastatic renal cell carcinoma (RCC). Capecitabine is an orally administered prodrug that is converted to fluorouracil and is of potential use in the treatment of this disease. We conducted a Phase II clinical trial of capecitabine administered as a single agent to patients with metastatic RCC. The treatment consisted of 1250 mg/m2 capecitabine orally, twice daily (2500 mg/m2 per day) days 1–14, repeated every 21 days. There were 15 patients, including 13 men and 2 women, who underwent a total of 67 cycles (median 3.5; range 1–15). Nine patients had undergone prior systemic therapy consisting of interferon-α in 3, interleukin-2 in 1, interferon-α plus interleukin-2 in 4, and investigational therapy with bryostatin-1 in 1. There were 14 patients assessable for response (one withdrew), and no responses were seen. Median time to progression was 9 weeks (range 1–45). There were 3 patients (21%) who had stable disease for 18, 39, and 45 weeks. Hematologic toxicity was mild. Three patients had grade 3 or 4 gastrointestinal toxicity, and 3 required dose reductions. There were 2 early deaths, including 1 patient with pulmonary edema and 1 with hypotension. The study was terminated because there were no responses in the first 14 assessable patients, indicating that the response rate was likely to be less than 20%. We conclude that single-agent capecitabine has minimal activity for the treatment of metastatic RCC. [Copyright &y& Elsevier]
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- 2006
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47. Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer
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Pohl, Gudrun, Krajnik, Gerhard, Malayeri, Reza, Müller, Rolf-Michael, Klepetko, Walter, Eckersberger, Franz, Schäfer-Prokop, Cornelia, Pokrajac, Boris, Schmeikal, Susanne, Maier, Alfred, Ambrosch, Gerhard, Woltsche, Michael, Minar, Wilma, and Pirker, Robert
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CANCER patients , *LUNG cancer , *ANTINEOPLASTIC agents , *SMALL cell lung cancer - Abstract
Summary: Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol®175mg/m2 over 3h on day 1, ifosfamide 1000mg/m2 daily on days 1–3, cisplatin 60mg/m2 on day 1, and prophylactic filgrastim 5μg/kg daily on days 4–13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36–78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p =0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p =0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC. [Copyright &y& Elsevier]
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- 2006
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48. Rational drug sequencing of paclitaxel, gemcitabine and carboplatin in patients with untreated stage IV and select stage IIIB non-small cell lung cancer
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Sovak, Mika A., Lutzker, Stuart, Zheng, Ling, Guensch, Lisa, Joyce, Margaret, Schwartz, Susan, Wu, Yujun, and Aisner, Joseph
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CANCER treatment , *LUNG cancer , *ANTINEOPLASTIC agents , *PACLITAXEL - Abstract
Summary: Introduction: To conduct a phase II study evaluating the efficacy of rationally sequenced paclitaxel, gemcitabine, and carboplatin in patients with stage IV or select stage IIIB non-small cell lung cancer (NSCLC). Methods: Patients with select stages IIIB (pleural effusion) and IV NSCLC with an ECOG performance status of 0–1 and no prior chemotherapy for their disease were eligible to participate. Treatment was delivered as follows: paclitaxel at 70mg/m2 followed by gemcitabine at 300mg/m2 on day 1, with carboplatin (AUC 5) on day 2 of a 28-day cycle. Response was assessed after every two cycles of therapy. The primary endpoint of this trial was response rate, with secondary endpoints of time to progression and 1 year overall survival. Results: Twenty patients were enrolled on protocol, one of whom never received chemotherapy. The median number of cycles delivered was 3 (range 0–8). A partial response rate of 42% (8/19; 95% CI: 20–67%) and a stable disease rate of 11% (2/19; 95% CI: 1–33%) were observed. The median overall survival time was 9.6 months (95% CI: 4.6–16.6), with a 1 year overall survival rate of 42.1% (95% CI: 24.9–71.3%). Eight patients (42%) stopped treatment due to toxicity. Conclusion: Paclitaxel followed by gemcitabine and then carboplatin is an active, albeit complex, regimen in the treatment of patients with advanced NSCLC with insufficient advantage to justify continuation of this regimen. [Copyright &y& Elsevier]
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- 2006
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49. Clinical experience with the MammoSite® radiation therapy system for brachytherapy of breast cancer: Results from an international phase II trial
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Niehoff, Peter, Polgár, Csaba, Ostertag, Horst, Major, Tibor, Sulyok, Zoltán, Kimmig, Bernhard, and Kovács, György
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CANCER treatment , *CANCER patients , *THERAPEUTICS , *MEDICAL imaging systems - Abstract
Abstract: Background and purpose: In a prospective multi-center phase II trial, we investigated the MammoSite® Radiation Therapy System, a new device for delivering intracavitary brachytherapy following breast conserving surgery. The MammoSite® is a dual lumen, closed ended catheter with a small, spherical inflatable balloon and a port for connecting a remote afterloader to the central lumen. We analyzed the surgical procedure and placement of the MammoSite®, treatment planning and radiation delivery complications and cosmesis, as well the comfort for the patients. Patients and methods: Between 2002 and 2004 a total of 32 patients (pts) were implanted using the MammoSite®. The reference isodose was defined 1cm from the balloon surface. We analyzed the post-implant anatomic position of the applicator and the geometric form of the balloon via ultrasound, CT and X-ray, related side effects, cosmetic outcome and patient quality of life. Results: Twenty-three out of 32 patients (72%) were eligible for MammoSite® intracavitary brachytherapy. Twenty-eight percentage had to be excluded because of different reasons. Eleven patients were treated with primary brachytherapy with a total dose of 34Gy (2×3.4Gy) and 12 had a boost with a mean dose of 13.3Gy (range: 7.5–15Gy; 2×2.5Gy) combined with EBRT and doses ranged between 46 and 50Gy. In three cases a balloon rupture occurred. We observed two abscesses within 3 months of implantation and serious seroma development in 10 patients (39%). Skin related side effects were erythema in 21 patients (91%), hyperpigmentation in 13 patients (56%) and teleangiectasia in six patients (26%) after mean follow-up 20 months. Conclusions: The MammoSite® Radiation Therapy System is a feasible treatment modality for intracavitary brachytherapy of breast cancer after breast conserving surgery. The advantage of the system is only one applicator is necessary for the delivery of a fractionated radiotherapy. In addition, patient tolerance of the procedure is high. Critical issues concern possible overdosages at the skin reflected by a high rate of late skin damage after only 20 months of follow-up time. The method could serve as an alternative to conventional multi-catheter brachytherapy for a selected group of patients. [Copyright &y& Elsevier]
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- 2006
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50. Front-line treatment of advanced non-small cell lung cancer with irinotecan and docetaxel: A multicentre phase II study
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Ziotopoulos, Panagiotis, Androulakis, Nikolaos, Mylonaki, Efthimia, Chandrinos, Vassilios, Zachariadis, Emmanouel, Boukovinas, Ioannis, Agelidou, Athina, Kentepozidis, Nikolaos, Ignatiadis, Michail, Vossos, Andreas, and Georgoulias, Vassilis
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LUNG cancer , *CANCER patients , *ANTINEOPLASTIC agents , *DRUGS - Abstract
Summary: Purpose: : To evaluate the efficacy and tolerance of the irinotecan plus docetaxel combination in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: : Thirty-nine chemotherapy-naïve patients with advanced NSCLC were treated with irinotecan 200mg/m2 followed by docetaxel 80mg/m2 intravenously on day 1 with granulocyte colony-stimulating factor (150μg/m2) support from day 2 to 9. Treatment was repeated every 3 weeks. Results: : A partial response was achieved in 9 (23%; 95% confidence interval 9.85–36.3%) patients; stable and progressive disease were observed in 10 (25.6%) and 20 (51.4%) patients, respectively. The median duration of response was 7.1 months and the median time to tumor progression 3 months. The median survival time was 10.8 months and the 1-year survival 42.2%. Four (10.3%) patients developed grade 4 neutropenia and all but one were complicated with fever; there was no treatment-related death. Nine (23.1%) patients developed grade 3 or 4 diarrhea while grade 2 or 3 fatigue occurred in nine (23.1%), and grade 3 mucositis in two (2.6%). Conclusion: : The combination of irinotecan/docetaxel is a relatively active non-platinum-based chemotherapy regimen with manageable toxicity, which could be given in an outpatient basis; this regimen merits to be further studied in order to improve its tolerance and evaluate its clinical relevance in patients who can not tolerate platinum-based doublets. [Copyright &y& Elsevier]
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- 2005
- Full Text
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