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Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m 2 ) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10-1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastasis and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Immune checkpoint inhibitors have revolutionized cancer treatment in the last decade. Despite the progress in immunotherapy, most pancreatic cancer patients still do not derive benefit when receiving immune-based therapies. Recently, resistance mechanisms to immune therapies have been mainly focused on tumor microenvironment properties. Pancreatic cancer is considered one of the most lethal and difficult to treat tumors due to its highly immunosuppressive and desmoplastic microenvironment. Low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thromboembolic disease in these patients. However, many nonanticoagulant properties attributed to LMWHs have been described. Exploiting LMWH properties in a combined treatment modality with immune checkpoint inhibition and chemotherapy could provide a new approach in the management of pancreatic adenocarcinoma patients. The ability of LMWH to interfere with various aspects of the tumor microenvironment could result in both the alleviation of immunosuppression and improvement in drug delivery within the tumor, leading to higher cancer cell destruction rates and more potent immune system activity that would, ultimately, lead to better patient outcomes., Competing Interests: The authors declare that there is no conflict of interest.

Background: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines., Patients and Methods: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months., Results: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m 2 ), trauma history, renal insufficiency and bevacizumab use., Conclusion: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy., Methods: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms., Results: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients., Conclusions: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice., Competing Interests: The authors EI, NT, KT, VM, PS, AS, EK, GT and GN declare that are employees in GeneKor MSA. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflicts of interest.

Pancreatic arteriovenous malformation (pAVM) is a very rare entity, as less than 100 cases are reported in the international literature. Patients with pAVM may be asymptomatic or may present a wide range of symptoms, such as vague pain, feeling of fullness, gastrointestinal bleeding, or even portal hypertension. We present the multimodality approach in the diagnosis of a patient with pAVM and treatment via transcatheter arterial embolization of the lesion using steel coils. The patient was free of symptoms 12 months later.

Ciclopirox olamine (CPX) is an antifungal agent that has recently demonstrated promising anti-neoplastic activity against hematologic and solid tumors. Here, we evaluated CPX compared with gemcitabine alone as well as their combination in human pancreatic cancer cell lines; BxPC-3, Panc-1, and MIA PaCa-2 and in humanized xenograft mouse models. We also examined the preclinical pharmacodynamic activity of CPX. CPX caused a pronounced decrease in cell proliferation and clonogenic growth potential. These inhibitory effects were accompanied by induction of reactive oxygen species (ROS), which were strongly associated with reduced Bcl-xL and survivin levels and activation of a panel of caspases, especially caspase-3, and finally resulted in apoptotic death. CPX-induced apoptosis was associated with reduced pEGFR (Y1068) and pAkt (Ser473) protein levels. Additionally, decreased proliferation was observed in CPX-treated xenografts tumors, demonstrating unique tumor regression and a profound survival benefit. Finally, we showed that CPX significantly abrogated gemcitabine-induced ROS levels in pancreatic tissues. These pre-clinical results have verified the superior antitumor efficacy of CPX over gemcitabine alone, while their combination is even more effective, providing the rationale for further clinical testing of CPX plus gemcitabine in pancreatic cancer patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest

Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.

Background: Sequential anthracyclines and taxanes are standard adjuvant chemotherapy for patients with high-risk axillary node-positive breast cancer. We compared a sequential to a concurrent regimen in high-risk node-negative early breast cancer., Methods: Patients were eligible if they had tumours >2 cm or T1c with two of the following characteristics: no oestrogen receptor (ER) and progesterone receptor (PR) expression, histological grade III, Ki67 >40% and vascular, lymphovascular or perineural invasion. They were randomised to receive four cycles of epirubicin 90 mg m -2 followed by four cycles of docetaxel 75 mg m -2 (sequential regimen) or six cycles of epirubicin 75 mg m -2 plus docetaxel 75 mg m -2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with G-CSF prophylaxis only for the concurrent arm. The primary endpoint was disease-free survival (DFS)., Results: Between 2001 and 2013, 658 women received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 years, 43.9% of the patients were premenopausal and of the tumours 44.2% were ⩽2 cm, 52.7% histological grade 3 and 35.3% hormone receptor-negative. After a median follow-up of 70.5 months, there were 29 (8.8%) vs 42 (12.8%) disease relapses (P=0.102) and 11 (3.3%) vs 19 (5.8%) deaths (P=0.135), in the sequential and concurrent arm, respectively. The 5-year DFS rates were 92.6% vs 88.2% for sequential and concurrent arm, respectively (hazard ratio (HR): 1.591; 95% confidence interval (CI): 0.990-2.556; P=0.055). Toxicity included grade 2-4 neutropenia in 54% vs 41% (P=0.001), febrile neutropenia 2.7% vs 6.1% (P=0.06), nausea/vomiting 18.5% vs 12.4% (P=0.03) of patients in the sequential and concurrent arm. There were no toxic deaths., Conclusions: Sequential compared with the concurrent administration of anthracyclines and taxanes is associated with a non-significant but possibly clinically meaningful improvement in DFS. In the era of molecular selection of patients for adjuvant chemotherapy, this study offers valuable information for the optimal administration of anthracyclines and taxanes in patients with node-negative disease.

Background: In this superiority study, pemetrexed was compared with erlotinib in pre-treated patients with metastatic non-small cell lung cancer (NSCLC)., Methods: Patients with stage IIIB/IV NSCLC who progressed after first-line or second-line treatment were randomized to receive either pemetrexed or erlotinib. In total, 21.7% of patients in the pemetrexed arm and 23.5% of patients in the erlotinib arm had squamous cell histology, and treatment was third line in 39.2% and 46.4% of patients, respectively. The primary study endpoint was time to tumor progression (TTP). Epidermal growth factor receptor/v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (EGFR/KRAS) mutation status also was investigated., Results: There was no difference in terms of the TTP (P = .195), the objective response rate (P = .469), or overall survival (P = .986) between the 2 treatment arms. In patients who had squamous cell histology, erlotinib resulted in a superior TTP compared with pemetrexed (4.1 months vs 2.5 months, respectively; P = .006). The incidence of grade 3 and 4 neutropenia, thrombocytopenia, and asthenia was significantly higher in the pemetrexed arm, whereas the incidence of grade 3 and 4 skin rash was higher in the erlotinib arm., Conclusions: Both pemetrexed and erlotinib had comparable efficacy in pre-treated patients with metastatic NSCLC, and the current results indicated that genotyping of tumor cells may have an important effect on treatment efficacy., (© 2013 American Cancer Society.)

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are known to have greater efficacy in EGFR mutation-positive non-small cell lung cancer (NSCLC), although erlotinib also has activity in wild-type disease. We report the successful long-term maintenance treatment of a patient with EGFR wild-type NSCLC with gefitinib and later erlotinib. The patient (male; 44 years old; smoker) was diagnosed with EGFR wild-type NSCLC after computer tomography had revealed a mediastinal mass, and histology and mutation testing had identified the tumor as an EGFR wild-type grade 3 adenocarcinoma. The patient received multiple rounds of chemotherapy, followed by gefitinib maintenance (3 years). Later on, he received erlotinib maintenance and developed a persistent rash (grade 1/2) that lasted throughout the treatment. The patient's condition has remained stable on erlotinib for more than 5 years, with no evidence of progression. We describe the patient's disease course and treatment in the context of EGFR TKI therapy and the prognostic factors for long-term clinical outcomes of NSCLC, including the development of erlotinib-induced rash.

Aim: To compare the efficacy and tolerance of sequential versus alternate front-line administration of cisplatin-etoposide (PE) and topotecan (T) in patients with extensive stage small cell lung cancer (SCLC)., Patients and Methods: Patients were randomized to receive either 4 cycles PE (cisplatin 80 mg/m(2) i.v. day 1 and etoposide100 mg/m(2)/d i.v. days 1-3 every 21 days) followed by 4 cycles T (1.5 mg/m(2)/d i.v. days 1-5 every 21 days) (arm A, 183 patients) or the same regimens using an alternate sequence (arm B, 181 patients)., Results: There was no significant difference in terms of compliance with treatment, overall response rates (51.4% vs. 55.2%; p=0.458), median response duration (4.3 vs. 5.2 months; p=0.780), median time to tumour progression (5.7 vs. 6.4 months; p=0.494), median overall survival (10.9 vs. 9.8 months; p=0.186) and 1-year survival (43.8% vs. 36.5%) between the two arms. The incidence of severe grade 3-4 haematological and grade 2-4 non-haematological (asthenia, mucositis, diarrhoea and neurotoxicity) toxicity was comparable between the two arms., Conclusion: The comparison of sequential versus alternate administration of cisplatin-etoposide and topotecan as front-line treatment of patients with extensive stage SCLC revealed no clinically meaningful differences in terms of efficacy and tolerance.

Oral topotecan has been recently brought into clinical practice at a dose of 2.3 mg/m(2) for 5 days, every 3 weeks. Published data show quite high myelotoxicity. The aim of this trial was to define the daily dose and treatment duration, which permits safe toxicity. The study was designed to begin at a low daily dosage of 1.5 mg/m(2) and was escalated by increasing the topotecan dose and the day-treatment duration. The plan was to end up with 2.3 mg/m(2) daily for 5 days. In cases of tolerability with the last dosage given, we would then continue testing a higher daily dosage. Treatment repetition was planned to be every 21 days. Dosage levels were 1.5, 2.0 and 2.3 mg/m(2) for 3 days, 2.0 and 2.3 mg/m(2) for 4 days, and 2.3 mg/m(2) for 5 days. Toxicity was scored according to the Common Toxicity Criteria. Thirty-two patients (27 male, five female, median age 60 years, range 46-77 years) with small-cell lung cancer were included. The patients on 1.5 and 2 mg/m(2) for 3 days showed no myelotoxicity. Four (25%) patients on 2.3 mg/m(2) 3-day treatment developed grade 3-4 neutropenia. Three of five patients (60%) treated for 4 days at a dose of 2.3 mg/m(2) developed grade 3-4 neutropenia and less than half (two of five, 40%) of these patients had thrombocytopenia. Eight patients (66.7%) on the 5-day treatment presented with serious grade 3-4 myelotoxicity. Two treatment-related deaths were observed in the 5-day group and one in the 4-day group. Granulocyte growth factor was applied in over 60% of the patients. In conclusion, a dose of 2.3 mg/m(2) for 5 days was intolerable. Dose-limiting toxicity was 2.3 mg/m(2) for 4 days without prophylactic granulocyte colony-stimulating factor administration. The safe duration of oral topotecan treatment and the maximum tolerated dose seem to be not longer than 3 days at a dose of 2.3 mg/m(2).

Background: Non-platinum-containing regimens have been proposed as alternatives to platinum-based doublets in the first-line treatment of patients with non-small cell lung cancer (NSCLC). However, conflicting results about their equivalence have been reported., Methods: We reviewed the records of patients enrolled in randomized controlled first-line trials conducted by the Hellenic Oncology Research Group from February 1997 to September 2006. The outcome of patients treated with first-line non-platinum-based chemotherapy who received platinum-based chemotherapy upon progression (cohort A) or platinum-based first-line chemotherapy followed by non-platinum-containing second-line chemotherapy (cohort B) was retrospectively analyzed., Results: Two-hundred and sixty-seven patients were identified in cohort A, and 123 in cohort B. Median follow-up time was 12.5 and 15.7 months for cohorts A and B. A significantly higher response rate and time to tumor progression (TTP) was recorded for patients treated with platinum-based compared to those receiving non-platinum-based first-line chemotherapy (45.5 vs. 21.3%, p < 0.0001 and 5.8 vs. 3.1 months, p= 0.002, respectively). Platinum-based regimens administered as second-line treatment resulted in a 13.1% response rate. TTP for second-line chemotherapy did not differ significantly between the two cohorts. Median overall survival was 13.3 and 15.7 months for cohorts A and B (p = 0.538)., Conclusion: Both sequences resulted in similar efficacy in terms of overall survival. Encouraging median survival was achieved for selected patients with NSCLC who received both first- and second-line chemotherapy., (Copyright 2010 S. Karger AG, Basel.)

Objectives: To compare the efficacy and safety profile of irinotecan (I) versus the combination of irinotecan/gemcitabine (IG) as second-line treatment of patients with extensive stage small-cell lung cancer (SCLC)., Treatment: Patients with SCLC who have received at least one chemotherapy regimen were randomized to receive either the IG regimen (gemcitabine 1000mg/m(2) intravenous (i.v.) on days 1 and 8 and irinotecan 300mg/m(2) i.v. on day 8) or I monotherapy (300mg/m(2) i.v. on day 1) both every 3 weeks., Results: Thirty-eight patients were enrolled in the IG and 31 in the I arm. Due to slow accrual an early closure of the study was decided. Response rate was significantly higher in the IG than in I arm (23.7% vs. 0%; p=0.004). The median time to progression (TTP) was 3.9 months (range: 0.5-14.5 months; 95% CI: 1.4-6.6) and 1.7 months (range: 0.5-9.9 months; 95% CI: 1.2-2.3) (p=0.010) for the IG and I arms, respectively. There was no difference in terms of median overall survival between the two arms (6.8 months and 4.6 months for the IG and I arm, respectively). The most frequent toxicities were grade III/IV neutropenia and grade III/IV diarrhea., Conclusions: Although the IG regimen seems to be more active than the I monotherapy, the premature closure of the study prevents the drawing of definitive conclusions.

The aim of this study was to evaluate the safety and activity of a gemcitabine-oxaliplatin combination (GEMOX) regimen in pretreated patients with advanced ovarian cancer. Twenty-seven platinum-refractory/resistant and 14 platinum-sensitive patients received gemcitabine 1500 mg/m2 intravenously in days 1+8 and oxaliplatin 130 mg/m2 in day 8 every 21 days. Ten responses (one complete, nine partial) were observed; five in platinum-sensitive and five in platinum-resistant tumors. Grade 3-4 neutropenia and thrombocytopenia were observed in 17 and 10 patients, respectively. There were two treatment-related deaths due to thrombocytopenia and non-neutropenic sepsis. The GEMOX regimen has moderate activity in both platinum-sensitive and resistant ovarian cancer and a toxicity profile that can be significant and therefore requires careful monitoring.

Purpose: To evaluate the activity and tolerance of gemcitabine in combination with oxaliplatin (GEMOX regimen) in pretreated patients with advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Thirty-two patients with advanced NSCLC who had disease progression after a cisplatin- and taxane-based front-line regimen were treated with gemcitabine (1500 mg/m(2) on days 1 and 8) and oxaliplatin (130 mg/m(2) on day 8) every 3 weeks. The patients' median age was 62 years and the performance status (WHO) was 0 for 11, 1 for 17 and 2 for 4 patients. The treatment was second line for 22 (69%) and >or=third line for 10 (31%) patients., Results: Partial response was achieved in 5 (16%) patients, stable disease in 8 (25%) and progressive disease in 19 (59%). Two patients with stable disease and one patient with progressive disease while on previous chemotherapy experienced a partial response with GEMOX regimen. The median duration of response was 2.5 months (range, 1-11.5), the median time to tumor progression 3 months (range, 1-18) and the median survival 5.6 months (range, 1-31). Grade III neutropenia occurred in five (16%) patients, grade III thrombocytopenia in two (6%) and grade III anemia in three (9%); moreover, grades II-III asthenia was reported in eight (25%) patients and grades II-III neurotoxicity in three (9%)., Conclusion: The GEMOX combination is a relatively active and well tolerated second-line regimen in NSCLC patients pretreated with a taxane- and/or platinum-based chemotherapy.

Purpose: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC)., Patients and Treatment: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks., Results: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent., Conclusions: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.

Cisplatin or carboplatin plus paclitaxel is considered the standard first-line treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first-line chemotherapy by incorporating new promising agents led to sequential drug administration with two or three doublets. In the present study, we aimed to evaluate the activity and the tolerance of two sequential doublets (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as first-line treatment in patients with FIGO III/IV ovarian cancer. Treatment consisted of four cycles of carboplatin (6 AUC) plus paclitaxel (175 mg/m2; PC regimen) followed by four cycles with carboplatin (6 AUC) plus liposomal doxorubicin (40 mg/m(2); LD/C regimen) every 3 weeks. Forty-one patients in FIGO III or IV were enrolled. In an intention-to-treat analysis, 20 (49%) complete (CR) and 12 (29%) partial (PR) responses were achieved (overall response rate, ORR: 78%; 95% confidence interval, CI: 64.1-91.9%); with the PC regimen (164 cycles); 7 (17%) patients have stable (SD) and 2 (5%) progressive (PD) disease. The LD/C regimen (124 cycles) was administered in 36 (88%) patients because of 2 early deaths and 3 patient withdrawals. Three additional patients, 2 with PR and 1 with SD after PC chemotherapy) achieved a CR. Upon completion of the LD/C chemotherapy there were 18 (44%) patients with CR and 9 (22%) with PR (ORR=66%; 95% CI: 64-92%). The median duration of response was 27 months and the median time to progression 20 months. The probability of 2-year survival was 67%. Grade 3 and 4 neutropenia was observed in 34 and 14.6% of the patients, respectively, during the PC regimen, while during the treatment with LD/C the percentages for grade 3 and 4 neutropenia were 44.4 and 19.4%, respectively. Febrile neutropenia occurred only in patients treated with the PC regimen (4.9%). The incorporation of liposomal doxorubicin in this sequential doublet schedule of first-line treatment of ovarian carcinoma created a feasible and active regimen. Prospective randomized studies are required to assess its efficacy on patient survival., (Copyright (c) 2005 S. Karger AG, Basel.)

Purpose: To compare the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone., Patients and Methods: Chemotherapy-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m(2) on day 1, cisplatin 80 mg/m(2) on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 microg/m(2)/d on days 3 to 9) or D (n = 152; 100 mg/m(2) on day 1 without rhG-CSF) every 3 weeks., Results: The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P =.004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P =.200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P =.580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P =.0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P =.0001), diarrhea (P =.007), neurotoxicity (P =.017), and nephroroxicity (P =.006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P =.098)., Conclusion: DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.

Purpose: To evaluate the efficacy and toxicity of the combination of gemcitabine and docetaxel in pretreated patients with small-cell lung cancer (SCLC)., Patients and Methods: Twenty-two pretreated patients (median age 61 years, PS: 0-1 in 77% and 2 in 23%) with limited or extensive stage disease were treated with gemcitabine 1000 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8, every 21 days. Fifteen (68%) of the 22 patients had received two prior regimens and fourteen (64%) were refractory to front-line chemotherapy., Results: All patients were evaluable for efficacy analysis. No complete or partial responses were observed. Disease stabilization was obtained in one (5%) patient. The median survival was 14 weeks and the six-month survival rate was 28%. WHO grade 2 and 3 toxicities were infrequent and easily manageable., Conclusion: The combination of gemcitabine and docetaxel was inactive as salvage treatment in this poor prognosis group of patients with SCLC.