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Introduction: This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and methods: Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results: A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions: This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS. [ABSTRACT FROM AUTHOR]

Background In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. Patients and methods In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS). Results 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients. Conclusion Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In a first-line study of advanced NSCLC, pemetrexed–cisplatin was more effective among patients with adenocarcinoma and large-cell carcinoma compared with gemcitabine–cisplatin (median survival of 11.8 versus 10.4 months, P =.005), while survival with pemetrexed–cisplatin was shorter than with gemcitabine–cisplatin in patients with squamous cell carcinoma. The comparability of pemetrexed–cisplatin to other commonly used regimens within histology subgroups needs to be explored. Methods: This retrospective analysis combined the patient-level data from three phase 3 randomized controlled trials that compared the efficacy of different third generation platinum- and non-platinum based doublets. Unadjusted median survival times and Cox covariate-adjusted treatment hazard ratio (HR) estimates were calculated. Overall results and subgroups by histological type were reported. Results: This combined analysis consisted of 3467 patients. In the overall analysis, adjusted HRs favored pemetrexed (HR <1.0) to each of the other 5 regimens, though none of these HRs were statistically significant. Among patients with non-squamous histology, pemetrexed–cisplatin produced favorable HRs to each of the other regimens, achieving statistical significance when compared with vinorelbine–cisplatin (HR=0.67; 95% confidence intervals [CI]: 0.50, 0.91) and gemcitabine–cisplatin (HR=0.85; 95% CI: 0.75, 0.97). Among patients with squamous histology, 4 of the 5 comparison regimens produced favorable HRs (HR >1.0) when compared with pemetrexed–cisplatin, with only the comparison with gemcitabine–cisplatin achieving statistical significance (HR=1.23; 95% CI: 1.00, 1.51). Conclusion: In the absence of randomized clinical trial data comparing pemetrexed–cisplatin to commonly used doublets in advanced NSCLC other than gemcitabine–cisplatin, this combined analysis of multiple trials provides estimates for such comparisons. [Copyright &y& Elsevier]

Background: The efficacy and safety of weekly carboplatin (CBDCA) and gemcitabine (GEM) was evaluated as first-line chemotherapy with advanced non-small cell lung cancer (NSCLC). Methods: 46 chemotherapy-naive patients with measurable NSCLC were enrolled. Patients underwent a combination chemotherapy of GEM 1,000 mg/m2 plus CBDCA at an area under the curve of 2 on days 1 and 8 every 3 weeks. Results: Response rate was 30% (14/46; 95% confidence interval: 17.7-45.8%). The median number of treatment cycles was 3 (range 1-2). Time to progressive disease was 19.4 weeks and the median survival was 46.3 weeks. The 1-year survival rate was 46.9%. The major toxicity was hematotoxicity: grade 3 or 4 neutropenia (58.7%) and thrombocytopenia (45.7%). There were no other severe toxicities. Conclusion: Weekly chemotherapy with CBDCA plus GEM is a well-tolerated and promising regimen as first-line treatment of advanced NSCLC. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the activity and toxicity of two sequential chemotherapy regimens in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Methods: Eighty-eight chemonaive patients with stage IIIB/IV NSCLC were randomised to receive either three cycles of 75 mg/m cisplatin plus 75 mg/m docetaxel, both administered on day 1 every 21 days, followed by three cycles of 1,200 mg/m gemcitabine on days 1 and 8 every 3 weeks (arm A), or three cycles of 25 mg/m cisplatin plus 25 mg/m docetaxel on days 1, 8 and 15 every 28 days, followed by three cycles of 1,200 mg/m gemcitabine on days 1 and 8 every 3 weeks (arm B). Results: Of the evaluable patients, 61% in arm A ( n = 41) and 36% ( n = 44) in arm B completed treatment as per the protocol. The best tumour response rates were as follows (arm A and arm B): complete response: 2.4 and 2.3%; partial response: 39 and 20.4%; stable disease: 26.8 and 13.6%; and progressive disease: 31.8 and 45.4%. The median progression-free and overall survival were 3.9 and 12.3 months in arm A, respectively, 3.1 and 7.7 months in arm B. Grade 3-4 adverse events were more common in arm A. Grade 3-4 neutropenia was the main toxicity observed (56.1% in arm A and 11.4% in arm B). Conclusions: Our data demonstrate the feasibility of a sequential approach of cisplatin plus docetaxel followed by single-agent gemcitabine. Weekly administration of platinum-docetaxel is associated with an improved safety profile but lower efficacy than the conventional three-weekly schedule (registration ID 2004-001044-72). [ABSTRACT FROM AUTHOR]

Abstract: Background: Metastatic breast cancer (MBC) patients with rapid disease relapse after neo/adjuvant chemotherapy including anthracyclines and taxanes have limited treatment options and their efficacy is marginal. Two phase III studies compared ixabepilone plus capecitabine vs. capecitabine alone as first-line treatment in MBC patients pretreated with anthracyclines and taxanes in the neo/adjuvant setting. Here we report the efficacy and safety of these treatments in a prespecified subset of patients whose disease relapsed within 12 months. Patients and methods: Of 1973 patients across two studies, 293 relapsed within 12 months of neo/adjuvant treatment and received ixabepilone plus capecitabine (n = 149) or capecitabine alone (n = 144) as first-line chemotherapy for MBC. Analysis included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and toxicity. Results: In 293 patients, ixabepilone plus capecitabine, as compared to capecitabine alone, increased PFS (median: 5.6 months vs. 2.8 months; hazard ratio, 0.58; p < 0.0001), ORR (46% vs. 24%) and OS (median: 15.1 months vs. 12.5 months; hazard ratio, 0.84; p = 0.208). Major toxicities of this regimen included neuropathy, neutropenia and hand-foot syndrome, but were manageable. Conclusions: Patients with breast cancer with early relapse following neo/adjuvant treatment with anthracyclines and taxanes may benefit from ixabepilone plus capecitabine. (ClinicalTrials.gov identifiers: NCT00080301 and NCT00082433.) [Copyright &y& Elsevier]

Background: Many studies have investigated the efficacy of Endostar combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is a meta-analysis of available evidence. Methods: Fifteen studies reporting Endostar combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of Endostar combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 14.7% and 13.5% improvement, respectively (P < 0.00001). In addition, the time to progression (TTP) and quality of life (QOL) were improved after the treatment of Endostar combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, hepatic toxicity, and nausea/vomiting. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Endostar combined with PBDC was associated with higher RR, DCR, and TTP as well as superior QOL profiles compared with PBDC alone. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone. [ABSTRACT FROM AUTHOR]

The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5′UTR variable number tandem repeat, TYMS 3′UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade≥2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only. [ABSTRACT FROM AUTHOR]

Introduction: This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and methods: Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results: A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions: This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS. [ABSTRACT FROM AUTHOR]

Abstract: Background: Thymic carcinoma is a rare, malignant mediastinal tumor that is definitively distinguished from thymoma by its wide extensiveness and poor prognosis. At present, cisplatin-based triplet or quartet chemotherapy with the second generation antitumor agents, referred to as Einhorn''s protocol for germ cell tumors, is used as first-line chemotherapy for advanced thymic carcinoma, though an optimal chemotherapeutic regimen has not yet been established. In this retrospective study, the effectiveness and toxicity of cisplatin and irinotecan combination chemotherapy were evaluated over a nine-year period. Patients and methods: Patients with advanced thymic carcinoma who were treated with cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2010, were retrospectively identified from our database and medical records. The endpoints in this study were disease control, response rate, progression-free survival (PFS), and overall survival (OS). Significant hematological and non-hematological toxicities were also assessed. Results: Among identified nine patients, disease control was achieved in 8 patients (88.9%), and a clinical response was achieved in 5 (55.6%). The median PFS was 7.9 months, and the median OS was 33.8 months. One- and two-year OS were 77.7% and 55.6%, respectively. Grade 3/4 hematological toxicities were observed in 2 patients (22.2%), and Grade 3/4 non-hematological toxicities were seen in 2 patients (22.2%). No febrile neutropenia or toxic death was recorded. Conclusion: Cisplatin and irinotecan combination chemotherapy appears to be acceptable for advanced thymic carcinoma as first-line chemotherapy with respect to efficacy, toxicity, and usage in the clinical setting. [Copyright &y& Elsevier]

Purpose: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin in combination with levofolinate and infusion 5-fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with unresectable metastatic colorectal cancer. Methods: Sixty consecutive patients with histologically confirmed advanced or metastatic colorectal cancer were enrolled in the study. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred. Results: Two patients were ineligible. Toxicity was evaluated in 60 patients, who had received a part or all of the protocol therapy. A partial response was observed in 20 patients. The overall response rate was 34.5% (95% CI, 22.5%-48.1%) and the tumor control rate (partial response + stable disease) was 82.8%. The median progression-free survival was 6.9 months (95% CI, 5.1-9.8 months), and the median overall survival was 31.5 months (95% CI, 18.1-40.1 months). There were no toxicity-related deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a delay in the subsequent treatment course. Mild to moderate cumulative peripheral sensory neuropathy affected 71.7% of patients. Conclusion: The results showed good tolerability and efficacy for first-line FOLFOX4 in the treatment of patients with advanced colorectal cancer, indicating the promise of this regimen as first-line therapy for advanced colorectal cancer in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: A combination of fluorouracil and leucovorin (5-FU/LV) with oxaliplatin (FOLFOX) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. A strategy to stop FOLFOX, deliver 5-FU/LV as a maintenance therapy and reintroduce FOLFOX was found to be equivalent in terms of efficacy while neurotoxicity was substantially reduced. The aim of this study was to evaluate feasibility of a stop-and-go strategy with S-1, an oral fluoropyrimidine derivative, as a maintenance therapy administered between modified FOLFOX6 (mFOLFOX6) as a first-line treatment of mCRC. Methods: Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 followed by maintenance therapy with oral S-1. Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or upon tumor progression. The primary endpoint was duration of disease control (DDC). Results: Twenty-one of the 30 patients who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in 15 patients. Median DDC and progression-free survival were 9.3 and 7.9 months, respectively. The response rates and disease control rates were 40.0 and 86.6% for the initial mFOLFOX6, 23.8 and 57.1% for S-1 maintenance therapy and 20.0 and 73.3% for mFOLFOX6 reintroduction, respectively. Twenty-eight patients (93.3%) had peripheral neuropathy, but grade 3 neurotoxicity was observed in only 1 patient (3.3%). Conclusion: The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible as a first-line treatment for Japanese mCRC patients. Further prospective randomized control study is warranted. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin (DXP) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer. Methods: Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine (days 1-14) and intravenous docetaxel and cisplatin (day 1) every 3 weeks. Results: In the phase I study, 15 patients were treated with 4 different dose levels. Asthenia and neutropenic fever were the dose-limiting toxicities. For the phase II study, 1,125 mg/m of capecitabine was initially recommended with 60 mg/m docetaxel and 60 mg/m cisplatin. However, frequent dose modifications at this dose level resulted in a final optimal dose of 937.5 mg/m capecitabine. Among the 40 patients enrolled in the phase II study, 4 complete and 23 partial responses were observed, presenting objective response rate of 68%. Ten patients achieving good response with complete disappearance of distant metastases underwent surgery, and 4 pathologic complete responses were identified. After the median follow-up of 83.7 months (range, 20.2-86.5) in surviving patients, the median overall survival was 14.4 months and median progression-free survival was 7.6 months. The most frequent grade 3/4 adverse events were neutropenia (62.5%) and asthenia (37.5%). Ten per cent of the patients experienced neutropenic fever, with one case of sepsis-induced death. Conclusion: DXP displays considerable antitumor activity, and may thus present effective first-line treatment for advanced gastric cancer. Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant settings is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, randomized trials have recently demonstrated the efficacy of several new drugs (pemetrexed, bevacizumab, cetuximab, erlotinib, gefitinib) in this setting. Hence, the choice of optimal treatment is no longer limited to the different platinum-based doublets. In order to guide clinical management of patients with advanced NSCLC, assess the strengths and limitations of available evidence, and to suggest priorities for clinical research, the Italian Association of Thoracic Oncology organized an International Expert Panel Meeting on the first-line treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2009. Experts recommended that every effort should be made to obtain adequate tumor tissue before initiating treatment. Tumor histology/cytology subtyping is now important for the correct choice of treatment. In particular, considering efficacy data obtained with pemetrexed and safety concerns with bevacizumab, a division between squamous and non-squamous tumors is necessary. Epidermal growth factor receptor (EGFR) mutation analysis, at present, is not recommended in all patients, but should be performed in subgroups of patients characterized by higher prevalence of sensitizing mutations (Asians, never smokers, women, adenocarcinoma). When a mutation is present, first-line treatment with single-agent EGFR tyrosine-kinase inhibitor may be considered. Finally, the potential benefit of maintenance treatment for patients without progression at the end of first-line should be carefully discussed with each patient. Although the number of treatment options for patients with advanced NSCLC has increased recently, their results remain modest and further research is mandatory. [Copyright &y& Elsevier]

OBJECTIVE: To probe into the clinical efficacy of pemetrexed combined with cisplatin as first-line chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer. METHODS: 68 patients with advanced non-small cell lung cancer undergoing chemotherapy admitted from Jan. 2010 to Dec. 2015 were selected to be divided into observation group and control group via the throwing dice method, with 34 cases in each.The observation group were treated with pemetrexed combined with cisplatin, while the control group were given cisplatin combined with docetaxel, the efficacy, 1, 3 and 5 year survival rate, changes of tumor size and safety of two groups were observed. RESULTS: The total control of observation group was 79.41% (27/34), significantly higher than that of control group 52.94% (18/34), with statistically significant difference (P<0.05). The 5 year survival rate of observation group was 41.18% (14/34), significantly higher than that of control group 17.65% (6/34), with statistically significant difference (P<0.05). There were 7 cases (20.59%) with increase of the tumor size in observation group, while in control group was 16 cases (47.06%), with statistically significant difference (P <0.05). The incidence of bone marrow inhibit and liver function damage of observation group were lower than those of control group, with statistically significant difference (P <0.05). CONCLUSIONS:The efficacy of pemetrexed combined with cisplatin in treatment of elderly patients with advanced non-small cell lung cancer is significant, with high safety, which is worthy of application in clinic. [ABSTRACT FROM AUTHOR]

Background: This phase II study evaluated the clinical benefit of pegylated liposomal doxorubicin (PLD) and docetaxel (Taxotere) as first-line therapy for metastatic breast cancer (MBC). [ABSTRACT FROM PUBLISHER]

Background: Primary treatment goals in less aggressive metastatic breast cancer (MBC) are prolonged survival, good quality of life and control of the disease and its symptoms. High activity, oral administration and no alopecia make capecitabine monotherapy attractive in slowly evolving disease. Methods: We retrospectively analysed 226 patients who had received single-agent capecitabine as 1st-line chemotherapy at our institution. Results: The median interval between breast cancer diagnosis and MBC was 52 months (range 0–479); 76% had received endocrine therapy for MBC, 58% had visceral involvement and 30% had 3 or more metastatic sites. The median starting dose was 1,000 mg/m2 twice daily. Disease was improved in 56% of the patients (median duration: 13.2 months) and stabilised in 20%. Median time to treatment failure was 8.8 months (95% CI: 7.1–10.5); median overall survival from initiating capecitabine was 23.6 months (95% CI: 19.7–27.4). Prior adjuvant chemotherapy, endocrine therapy for MBC, visceral disease, hormone receptor status and initial capecitabine dose did not influence time to treatment failure. Among 161 patients <75 years, 90% received further chemotherapy. Conclusion: Based on these findings, 1st-line capecitabine should be considered in slowly progressing disease, offering an active, well-tolerated oral treatment with minimal toxicity and no alopecia. More toxic treatments may be reserved for more aggressive disease. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To test toxicity, tolerability, time to progression, survival and response rate in the 3-day administration of topotecan (T) followed by carboplatin (C), and then etoposide (E) in a study for small cell lung cancer (SCLC) treatment. Patients: 44 chemotherapy-naive patients with SCLC (median age 63.5, PS 0–1). ED was present in 28 patients. Methods: Each treatment cycle consisted of T (0.8mg/m2 on days 1–3), C (AUC=5, day 3) and a standard oral dose of E (100mg on days 15–17). Cycles were repeated every 32 days and up to eight were performed. Responders received radiotherapy to the primary site (50Gy) after the 4th cycle and complete responders also received PCI. Results: Complete response (CR) was achieved in 4 patients, partial response (PR) in 18, stable disease in 10 and PD in 12. Median survival was 280 (±36.7) days and median time to progression 137 days. 11 patients developed grade 3/4 neutropenia and 3 patients grade 3/4 anaemia. Non-haematological toxicity was mild. Conclusion: In contrast to ORR, PFS and survival were quite similar to those of SCLC patients suffering from ED treated by a platinum–etoposide regimen. The T/C/E combination was well tolerated and with low toxicity, but without improvement in the ORR and survival in comparison to platinum analogue regimes. [Copyright &y& Elsevier]

Summary: Germ cell tumors (GCTs) account for the majority of testicular cancer cases occurring in men of young age and are divided into two main histologic groups, seminomas and non-seminomas. The introduction of cisplatin in the treatment of germ cell tumors was a breakthrough, classifying them among curable diseases. The identification of 3 subgroups of patients with non-seminomatous tumors (good-risk, intermediate and poor-risk), with different profiles concerning prognosis and response to treatment, supported clinical trials aiming to assess different treatment strategies and recommend the most effective and less toxic regimens. This review describes the toxic effects of therapy and the efforts aiming to overcome toxicity and improve treatment efficacy, focusing on the trials which form the basis of current standard treatment of non-seminomatous germ cell tumors. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of this work was to explore the value of serum vascular endothelial growth factor-A (VEGF-A) in patients with metastatic triple negative breast cancer (TNBC) treated with chemotherapy. The primary end point was overall survival (OS). Secondary end points were response rate (RR), progression-free survival (PFS) and VEGF-A level at baseline, mid-therapy and at the end of therapy. Design and methods: Female patients aged 18 years or above with histologically proven metastatic TNBC were included. Serum VEFG-A levels were measured at baseline, after the 3rd and 6th cycles of FAC chemotherapy regimen (Fluorourcil, Adriamycin, and Cyclophamide). Results: The overall RR was 57%. The median PFS and OS were 7 and 11.2 months, respectively (95% CI: 4.3–9.7 and 3.8–18.5 months, respectively). Patients whose disease progressed despite therapy had a significantly higher baseline VEGF-A level than those who did not progress. VEGF-A level did not drop with continuation of therapy. Patients with high VEGF-A level had a significantly lower PFS but not OS than patients with low levels. Conclusion: The outcome of metastatic TNBC is poor with FAC chemotherapy regimen. Alternative chemotherapeutic regimens and novel therapeutic approaches including targeting of VEGF and/or its receptors are warranted. [Copyright &y& Elsevier]

The article presents a study that aims to analyze pathological and clinical prognostic factors in patients with primary fallopian tube carcinoma (PFTC). The study shows that reactivity for vascular endothelial growth factor was observed in 85% of specimens and progesterone receptors in 27%. Regarding clinical prognostic factors, the hazard ratio for advancement and death for patients with tumor residue >2 centimeter was 5.24 and 11.19.

Abstract: Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been reported to have a certain anti-tumor effect in previously treated patients with non-small cell lung cancer (NSCLC). However, the prognostic factors in those patients with and without a positive response to gefitinib treatment remain unclear. A retrospective chart review was performed in 131 advanced NSCLC patients who received 250mg of gefitinib as either a second-line or even later stage treatment from July 2002 to December 2005. The clinical factors including age, gender, performance status (PS), stage, histology, the number of prior types of chemotherapy, and the response to first-line chemotherapy were analyzed. One and 38 patients experienced a complete and partial response, respectively, to gefitinib treatment with an overall response rate of 30%. The median survival time (MST) of all patients receiving gefitinib treatment was 10 months while the MST was 28 months in the 39 gefitinib responders and 6 months in the 92 non-responders. Among the 39 gefitinib responders, the predominant prognostic factor was found to be the effectiveness of the first-line chemotherapy. The MST of the 20 patients with a response to the first-line chemotherapy was 32 months while the MST of the 19 patients without a response to the chemotherapy was 22 months (p =0.025). Among the 92 gefitinib non-responders, the predominant prognostic factor was the PS (p <0.001). The effectiveness of the first-line chemotherapy was therefore found to be a prognostic factor in the gefitinib responders with previously treated NSCLC, while the PS was shown to be a prognostic factor in the gefitinib non-responders. [Copyright &y& Elsevier]

The efficacy and toxicity of combined paclitaxel (PTX) and gemcitabine (GEM) was evaluated as a protocol for first-line chemotherapy in 40 patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel, 100 mg/m2, was administered intravenously (IV) as a 1-h infusion, followed by GEM, 1,000 mg/m2, IV over 30 min on days 1 and 8 of a 21-day cycle. The median age of patients was 66 years with a range of 33–75 years. Nearly all patients (39/40) had an ECOG performance status of 0 or 1. Thirteen patients (32%) had initial stage IIIB disease and 27 patients (68%) had stage IV disease. Histological subtypes were adenocarcinoma (73%) and squamous cell carcinoma (25%). Twenty-two patients (55%) achieved a partial response and none achieved a complete response, giving an overall response rate of 55% (95% confidence interval: 38.2–71.8%). Disease stability was achieved in 14 patients (35%), and 4 patients (10%) had progressive disease. The median survival time was 11.9 months (95% CI: 10.3–14 months), with a 1-year survival rate of 47.5%. Grade 3 or 4 hematological toxicities observed included neutropenia in 37.5%, anemia in 2.5%, and thrombocytopenia in 5.0% of these patients. Non-hematologic toxicities were mild, with the exception of grade 3 and 4 pneumonitis. There were no deaths due to toxicity. Weekly chemotherapy with PTX plus GEM is effective and is acceptable for the first line treatment of advanced NSCLC. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the value of telomerase activity (TA) in the detection of early recurrence in primary epithelial ovarian cancer (EOC). It states that TA was studied in ascites in EOC patients and peritoneal washings with saline solution in control subjects. It suggests that there was no relation between TA levels at second-look surgery and early recurrence of EOC.

The goal of treatment for patients with advanced breast cancer is to prolong survival, control symptoms, and reduce disease-related complications. Despite the introduction of many cytotoxic agents during the past decade, only modest improvement in survival in metastatic breast cancer has been achieved. In order to improve this situation, new cytotoxic drugs as well as molecule-targeted agents are now under investigation. Bendamustine is a bifunctional alkylating agent with cytotoxic activity against several types of solid tumors. In the search for new anthracycline-free combinations, taxanes and alkylating agents might be worth investigating, in order to reduce cardiac toxicity. In this article, we reviewed the latest information regarding antitumor activity, toxicity, pharmacokinetics, and clinical application of bendamustine as a cytotoxic agent in metastatic breast cancer. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cisplatin combined with 5-fluorouracil (5-Fu) is widely used in the management of advanced nasopharyngeal carcinoma (NPC). However, catheters and pumps are necessary for the continuous infusion of 5-Fu, which add to the cost, immobility and inconvenience of treatment. Capecitabine, an oral fluoropyrimidine, is a potentially more active and more convenient substitute to 5-Fu. A phase II study was conducted to evaluate the efficacy and safety of a capecitabine and cisplatin combination in metastatic NPC. In the multicenter, open-label, single-arm phase II study, patients with metastatic NPC who previously received no palliative chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m2 twice daily from day 1 to 14) and intravenous cisplatin (80 mg/m2, day1) every 3 weeks. A total of 48 patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. There were 3 patients (6.3%) with complete response and 27 patients (56.3%) with partial response, giving an overall response rate of 62.5% (95% CI, 49.1–76.4%). The median duration of response in the 30 responding patients was 7.5 months (range 1.4–22.4 months). With a median follow-up period of 13.3 months (range 2.3–50 months), the median time to progression and median overall survival for all patients were 7.7 months (95% CI, 6.3–9.2 months) and 13.3 months (95% CI, 9.4–17.2 months), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (14.6%), anemia (4.2%) and thromocytopenia (2.1%), nausea (8.3%), vomiting (10.4%), diarrhea (8.3%), stomatitis (6.3%) and hand–foot syndrome (HFS) (4.2%). The combination of capecitabine and cisplatin is active and well tolerated as a first-line therapy for patients with metastatic NPC. [ABSTRACT FROM AUTHOR]

Abstract: Owing to the slow but sustained progress made in lung cancer treatment over the last 20 years, several therapeutic options are now available in the first-line setting as well as for patients who have progressed after one or more previous lines of treatment. Considering the growing array of choices currently confronting clinicians involved in the treatment of advanced non-small cell lung cancer (NSCLC), an effort should be made to define the optimal treatment option in each disease setting and to identify a logical therapeutic strategy after initial disease progression. This is especially crucial in the management of young, fit patients, who may be suitable candidates for two or more lines of therapy. At present, a rational treatment strategy for advanced NSCLC may be designed on the basis of patient clinicopathological features and rely on evidence from large, well-conducted clinical trials. In a near future the results of prospective validation studies will provide more sophisticated approaches for the classification of lung cancer patients, allowing clinicians to make individualised treatment decisions based on tumour molecular profile and on novel, more refined predictive/prognostic factors. [Copyright &y& Elsevier]

Summary: Background: The combination of alternate i.v./oral (hybrid) administration of vinorelbine (VNR) plus cisplatin (CDDP), followed by oral VNR, could result in a more suitable first-line regimen for patients (pts) with advanced non-small cell lung cancer (aNSCLC) in the outpatient setting. Methods: The induction treatment consisted of CDDP 80mg/m2 i.v. and VNR 25mg/m2 i.v. day 1 and VNR 60mg/m2 oral day 8, every 3 weeks for 4 courses. A dose escalation of VNR to 80mg/m2 oral from day 8 of the second course and to 30mg/m2 i.v. from day 1 of the third course was planned in the absence of G3–4 toxicity. Pts with disease control after 4 courses underwent consolidation treatment with oral VNR 80mg/m2 days 1 and 8 every 3 weeks up to intolerance or progression. Results: Fifty-three pts entered the study: 80% males; median age 63 years (range 43–71); median ECOG PS 0 (range 0–1); histotype: adenocarcinoma 59%, epidermoid 31%, undifferentiated 10%; disease stage: IIIB 22%, IV 70%, recurrent disease 8%. The objective response was as follows: 1 (2%) CR, 20 (38%) PR, 16 (30%) SD, 11 (21%) PD and 5 (9%) pts were not assessable. Median TTP and OS were 6 and 10 months, respectively. G3–4 neutropenia was observed in 23 and 24% of pts in the induction and in the consolidation phases, respectively, with febrile neutropenia in 6 pts (11%) and 2 (8%), respectively. G3–4 non-haematological toxicity was rare, being represented by nausea–vomiting and neurotoxicity in 3 pts (6%) in the induction phase. Conclusions: This combination regimen including hybrid administration of VNR plus CDDP is feasible, tolerable and effective as a first-line treatment in pts with aNSCLC. [Copyright &y& Elsevier]

To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77-93%) in the CIP arm and 90% (95% CI 84-96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach. [ABSTRACT FROM AUTHOR]

To study the toxicity and efficacy of weekly paclitaxel and carboplatin (PC-W) in women with primary ovarian cancer This investigation extended a phase-I dose finding study and was approved by the institutional review boards of all participating institutions. Between 1999 and 2003, women with radically resected ovarian cancer of FIGO stages II B to IV were enrolled at 17 German centres. Patients received weekly paclitaxel at a dose of 100 mg/m2, followed by carboplatin AUC 2. After a first treatment block consisting of six cycles of chemotherapy, patients had a treatment-free interval of 14 days, followed by a second block of six cycles. Treatment was completed by a 28-days break and a final block of six cycles. Altogether, 129 women with a mean age of 59 ± standard deviation 11 years entered the study. Most patients (82.9%) had serous papillary carcinoma of FIGO stage III (72.9%) and IV (20.9%). Participants received 1,851 cycles of chemotherapy; averaging 14.3 ± 4.3 cycles each patient. PC-W produced low rates of peripheral neuropathy (grade 3: 2.3%, 95% confidence interval [CI] 0.5–6.6%), with rapid recovery after 3 months. However, 72 patients had grade III/IV anaemia (55.8%, 95% CI 46.8–64.5%). There were 36 events of grade III/IV leukopenia (27.9%, 95% CI 20.4–36.5%). One patient sustained neutropenic fever. CA-125- and objective response was noted in 73.9% (95% CI 64.7–81.8%) and 55.6% (95% CI 41.4–69.1%) of patients. Median progression free and overall survival was 21 and 43 months, respectively. PC-W is feasible; a randomized study is warranted to compare this new regimen with conventional 3-weekly treatment. [ABSTRACT FROM AUTHOR]

The treatment decision for patients with metastatic breast cancer who have received anthracyclines within the course of adjuvant chemotherapy is troublesome, particularly if trastuzumab and hormonal treatment are not indicated. In the first part of this review we discuss the value of retreatment with anthracyclines, a topic that has been indirectly evaluated by retrospective studies with conflicting results and within a small phase III trial with a negative outcome. Evidence on liposomal anthracyclines is also reviewed. In the second part of the review, alternative options of first-line chemotherapy are discussed. These include taxanes as single agents, taxanes in combination with other cytotoxic drugs, combinations without anthracyclines and taxanes, and innovative treatments including target-based agents. Both the amount and the quality of evidence on these treatments are poor. Few phase III studies are available and most of them have been performed with registrative aims sponsored by the companies who own the winning drug. Beyond indications derived from such studies, there is a great need for more clinical research in this setting. [ABSTRACT FROM AUTHOR]

Summary: Sixty-three patients received capecitabine at 1000mg/m2 twice daily every 2 out of 3 weeks as first-line treatment for advanced disease at our institution. Forty-five patients (71%) had previously received adjuvant or neoadjuvant chemotherapy. The median number of capecitabine cycles administered was 5(1–40). Forty-eight patients had measurable disease with response rate (RR) of 29%. The median time to progression (TTP) was 18(2–122) weeks. Seven patients (11%) had TTP of >1yr, four of whom received more than 10(24–40) cycles of capecitabine. Thirty-seven percent of patients still needed dose reductions. Our retrospective audit is consistent with a previously published study which used a higher starting dose of capecitabine as first-line chemotherapy. For a subgroup of patients, capecitabine can result in a long TTP with minimal toxicity. The benefit of continuing capecitabine beyond a fixed number of cycles should be investigated further. Schedules using even lower doses of capecitabine for longer periods may also be of interest. [Copyright &y& Elsevier]

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m−2 week−1 and trastuzumab: 4 mg kg−1 on day 1 as a loading dose followed by 2 mg kg−1 week−1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6–12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4–32.6). This regimen was safe: grade 3–4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.British Journal of Cancer (2006) 95, 788–793. doi:10.1038/sj.bjc.6603351 www.bjcancer.com Published online 12 September 2006 [ABSTRACT FROM AUTHOR]

Objective: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients. Methods: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m2 day 1, leucovorin 200 mg/m2, 5-fluorouracil bolus 400 mg/m2 and 22 h 600 mg/m2 days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or stable disease (SD) then received oral capecitabine 2,500 mg/m2 days 1–14 every 3 weeks; L-HOP was reintroduced as soon as progression occurred. Results: Twenty-eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX-4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was 9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty-eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.1%). Conclusions: FOLFOX-4 stop and go and capecitabine maintenance chemotherapy was associated with a very low incidence of grade 3 neurotoxicity. Although the number of patients enrolled was far too low for a definite conclusion, RD and PFS were comparable to those usually reported in the treatment of MCC patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective. : To determine the toxicity and efficacy of combined therapy with cisplatin and prolonged infusion topotecan as front line therapy in women with epithelial ovarian cancer. Patients and methods. : Women with previously untreated, measurable and non-measurable epithelial ovarian cancer, stages Ic–IV were eligible. Patients were treated with cisplatin 75 mg/m2 on day 1, followed by topotecan 0.3 to 0.4 mg/m2/day given as a continuous infusion over 14–21 days, every 28 days. Dose levels and duration of infusion were adjusted for toxicity as appropriate. Patients were evaluated for response to treatment and treatment toxicity by standard NYGOG criteria. Results. : Sixty patients were enrolled. Among the 20 patients with post-surgical residual disease >2 cm, 80% [95% CI (56.3%, 94.3%)] demonstrated an objective response to therapy. The median progression-free survival for all 60 patients enrolled was 19.3 months with a median overall survival of 45.6 months given the median follow-up of 55 months (range 6–81 months). Five year survival is estimated to be 41%. Toxicity was observed in the first four patients treated with topotecan (0.4 mg/m2/day × 21 days) and dosing was continued at 0.3 mg/m2/day × 14 days thereafter. Of the 56 patients treated at the amended dose level, marrow suppression continued to be dose-limiting, with 86% of patients experiencing grade 3 or 4 neutropenia, 55% experiencing grade 3 or 4 thrombocytopenia and 50% of patients experiencing grade 3 or 4 anemia. Nonetheless, only 11/245 cycles administered were associated with febrile neutropenia and/or infection (8 port-related). Other non-hematologic toxicity was as expected. There were no treatment-related deaths. Conclusion. : This large, multicenter phase II study of prolonged infusion topotecan in combination with cisplatin demonstrated similar response, time to progression and survival compared with reported results of taxane and platinum combinations. Hematologic toxicity was greater but tolerated. Further studies investigating topotecan in combination with platinum therapy as a first line agent are warranted. [Copyright &y& Elsevier]

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m2. However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m2 docetaxel for the treatment of breast cancer. This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m2. [ABSTRACT FROM AUTHOR]

Background. To evaluate the efficacy of carboplatin and docetaxel combination in patients with advanced non-small-cell lung cancer. Methods. In a phase II study, patients with inoperable stage IIIB or stage IV non-small-cell lung cancer (ECOG performance status of 0 or 1) were treated with the combination of carboplatin AUC 5 mg/ml·min and docetaxel 80 mg/m2 administered once every 3 weeks. Results. A total of 45 patients were accrued to the study. The median age was 62 years and adenocarcinoma was the most common histology. Patients received a median of four cycles of chemotherapy. The objective response rate was 29% with a median survival of 11.9 months among evaluable patients. The 1-year survival rate was 47%. Febrile neutropenia (17%) was the most common hematological toxicity associated with the regimen whereas grade 3 fatigue (4%) was the major nonhematological toxicity. Conclusions. The combination of carboplatin plus docetaxel is well tolerated and is effective for the treatment of patients with previously untreated advanced or metastatic non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Paclitaxel is a cytotoxic agent with proven antitumour activity in metastatic breast cancer. Weekly administration of paclitaxel has demonstrated sustained efficacy together with a more favourable toxicity profile (e.g. less myelotoxicity) than the 3-weekly administration. This study evaluates the activity and toxicity of weekly paclitaxel (Taxol®) as first-line chemotherapy in elderly patients (>70 years of age) with hormone-refractory metastatic breast cancer. Patients with metastatic breast cancer received 80 mg/m2 paclitaxel administered weekly on days 1, 8 and 15 of a 28-day cycle. Additional cycles were given until disease progression, or unacceptable toxicity. A dose increase to 90 mg/m2 was allowed in the absence of toxicity. 26 Patients received a total of 101 cycles (median 4, range 1–11). 22 patients completed at least two cycles (six administrations). In 23 patients who were evaluable for response, there were 10 partial responses (38%), 9 patients with stable disease (35%), while 4 patients had disease progression (15%). The median duration of response was 194 days (>6 months). Overall treatment was relatively well tolerated, but 8 patients (32%) had to prematurely discontinue treatment because of fatigue. Neuropathy >grade 1 was noted only after five or more cycles in 4 patients. Weekly paclitaxel at this dose and schedule is an effective treatment regimen in the elderly patient with metastatic breast cancer, and is feasible, but yields relevant fatigue in a subset of patients. [Copyright &y& Elsevier]

Objectives: To assess the efficacy and tolerability of gemcitabine and paclitaxel as first-line treatment in advanced breast cancer. Methods: Patients with histologically confirmed metastatic or metastatic plus locally advanced breast cancer received gemcitabine 1,200 mg/m[sup 2] on days 1 and 8 and paclitaxel 175 mg/m[sup 2] on day 1 every 21 days for 8 cycles. Results: From December 1999 to August 2001, 45 patients, with a median age of 53.5 years (range, 22–77), received a total of 260 cycles. All were assessable for response and toxicity. Twenty-seven patients had prior adjuvant therapy. Hormonal receptor status was positive in 31.1% and negative in 40.0% of patients. Main metastatic sites included soft tissue (62.2%) and lung (53.3%). The objective response rate was 66.7%; complete response, 22.2%; partial response, 44.4%; stable disease, 15.6%; progressive disease, 17.8%. Median duration of response was 18 months and median time to tumor progression was 11 months. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia developed in 13.3% of patients, and 15.5% developed grade 3/4 mucositis. No treatment-related deaths occurred. Median overall survival was 19 months. Conclusion: Gemcitabine plus paclitaxel is an active combination with a favorable toxicity profile as first-line treatment for patients with advanced breast cancer. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose. In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated. Methods. Epirubicin (75 mg/m2) and docetaxel (75 mg/m2) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC. Results. The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7–12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure. Conclusions. The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile. [ABSTRACT FROM AUTHOR]

: ObjectiveThe goal of this study was to evaluate the efficacy and tolerability of irinotecan plus cisplatin as first-line chemotherapy in metastatic or recurrent cervical cancer.: MethodsChemotherapy-naive patients with metastatic or recurrent disease and at least one measurable tumor site received irinotecan (60 mg/m2 IV infusion over 90 min) on Days 1, 8, and 15, followed by cisplatin (60 mg/m2 IV over 90 min) on Day 1, every 28 days for a maximum of six cycles.: ResultsThirty patients were included in the response and toxicity analysis. The median age was 45 years (34–65). Nineteen patients had metastatic disease, 6 presented with locally recurrent disease, and 5 presented with locally recurrent plus metastatic disease. Seven patients were stage IVB at diagnosis. There were 2 complete and 18 partial responses and overall response rate was 66.7% (95% confidence interval: 47–85%). Stable disease was observed in 2 patients (6.7%) and progression in 8 (26.7%). Median time to relapse was 13.4 months, with a median survival time of 16.9 months. One-year disease-free survival and overall survival were 26.7 and 65.1%, respectively. Dose-limiting toxicity was observed in 4 patients (13.3%) with grade 3 renal toxicity. Nine patients (30%) developed grade 3 neutropenia, and only grade 1–2 acute and late diarrhea were observed in 20 and 40%, respectively. A patient developed pancolitis after the sixth cycle. There were no chemotherapy-related deaths.: ConclusionThe combination of irinotecan and cisplatin is a clinically active regimen for metastatic and/or recurrent cervical cancer with acceptable tolerability. [Copyright &y& Elsevier]

Purpose. To evaluate the efficacy and tolerability of a combination of vinorelbine (VNR) and docetaxel (DOC) as first-line chemotherapy in patients with metastatic breast cancer. Patients and methods. The study group comprised 40 women with untreated metastatic breast cancer with visceral (85%) and bone (70%) metastases. Of the 40 patients, 24 (60%) had previously received adjuvant chemotherapy, which had included anthracyclines in 12 patients (30%). Treatment consisted of VNR 25 mg/m2 on days 1 and 5, and DOC 75 mg/m2 on day 1 every 3 weeks. Depending on the neutrophil nadir (grade 3 or 4 neutropenia by WHO criteria) recombinant human granulocyte colony-stimulating factor (G-CSF) 5 µg/kg on days 2–4 and 6–13 was given for all subsequent treatment cycles. Results. The overall response rate (ORR) was 40% (95% confidence interval, CI 15–65). Six patients (15%) achieved a complete response (CR) and ten patients (25%) achieved a partial response (PR). Stable disease (SD) was observed in six patients (15%), and 18 patients (45%) had progressive disease (PD). The median duration of response was 8 months and the median predictive time to progression (TTP) was 6 months. The main toxicity was neutropenia grade 3 and 4 in 28 patients (70%). Febrile neutropenia requiring hospitalization occurred in 12 patients (30%). Grade 3 or 4 anemia was seen in two patients (5%) and grade 3 or 4 thrombocytopenia was seen in one patient (2.5%). Severe nonhematologic toxicity, except alopecia, was uncommon and included stomatitis in two patients (5%), vomiting in two (5%) and diarrhea in one (2.5%). There were no treatment-related deaths. Conclusions. The combination of VNR and DOC at the doses used in this study showed moderate activity as first-line chemotherapy in metastatic breast cancer. Neutropenia was considerable despite G-CSF administration. [ABSTRACT FROM AUTHOR]

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Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m[sup 2] of TMTX intravenously, then 24 h later 200 mg/m[sup 2] of FA (i.v.) and 500 mg/m[sup 2] of 5-FU (i.v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25–49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. To date there have been four large randomized studies in Western countries examining the role of combining cisplatin and paclitaxel as first-line treatment for ovarian cancer. A phase II study of paclitaxel and cisplatin in Japanese patients with advanced ovarian cancer was performed to determine the objective response rate and toxicity of this regimen. Methods. Previously untreated patients with stage III or IV ovarian cancer and a good performance status were eligible. Treatment consisted of paclitaxel 180 mg/m2 administered as a 3-h intravenous (i.v.) infusion followed by cisplatin 60 mg/m2 i.v. Treatment was repeated every 3 weeks for at least four cycles. Granulocyte colony-stimulating factor (G-CSF) was not routinely used. Results. Among 26 eligible patients, there were 4 complete and 17 partial responses, for an overall response rate of 80.8% (95% confidence interval [CI], 60.6% to 93.4%). One hundred and twenty-nine treatment cycles were administered to the 26 patients. Grade 4 neutropenia was observed in 64 treatment cycles (50%) and in 23 patients (88%). Thrombocytopenia was less common. The most common nonhematologic toxicities included neurotoxicity, fatigue, arthralgia/myalgia, and nausea/emesis. Conclusion. Paclitaxel plus cisplatin is a highly active regimen in patients with advanced ovarian cancer. The toxicities of this regimen are well tolerated. [ABSTRACT FROM AUTHOR]