Cisplatin plus gemcitabine with or without vinorelbine as induction chemotherapy prior to radical locoregional treatment for patients with stage III non-small-cell lung cancer (NSCLC): results of a prospective randomized study.

To evaluate possible improvement in objective response of adding vinorelbine (V) to the combination of cisplatin/gemcitabine (CG) in induction chemotherapy for stage III NSCLC, patients (n=154) aged < or =75 years, Karnofsky index > or =70%, were stratified by stage (IIIA versus IIIB) and randomly assigned to receive: C (50mg/m(2) i.v.) plus G (1250mg/m(2) i.v.) or CG plus V (25mg/m(2) i.v.). All drugs were administered on days 1 and 8 of an every 3-week cycle. At conclusion, local treatment (LT) with surgery and/or radiotherapy was scheduled. The results indicated that, following a median of 3 cycles, the overall efficacy was 65% in the CG and 61% in the CGV group. Most patients in both groups received radiotherapy as part of their LT. Pathological complete response was confirmed by surgery in 18% in the CG and 25% in the CGV group. Median progression-free survival was 368 days in the CG and 322 days in the CGV group. There were no statistically significant differences in toxicities between groups. We conclude that the CG and CGV combinations had similar efficacy and moderate toxicity, without accruing to the triplet combination.

Gemcitabine and vinorelbine (GV) versus cisplatin, gemcitabine and vinorelbine (CGV) as first-line treatment in advanced non small cell lung cancer: results of a prospective randomized phase II study.

The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.

Activity of carboplatin in patients with advanced non-small cell lung cancer pre-treated with a non-platinum combination.

To assess the efficacy of carboplatin when used as a single agent in patients with advanced non small cell lung cancer (NSCLC) and who are refractory to chemotherapy with a non-platinum combination, we recruited patients (n=40) NSCLC patients, 36 of whom were males, with an overall median age of 59 years (range 39-79) and Karnofsky Performance Status of 70% (range 60-90%). At baseline, the patients had a median of one disease site (range 1-3) and had received a median of one prior regimen (range 1-2). Carboplatin was administered (i.v.; AUC=6) every 3 weeks until disease progression or non-acceptable toxicity was reached. In total 169 cycles were administered (median 4 cycles/patient; range 1-8). Main toxicities were grade 2-3 anemia and grade 4 thrombocytopenia (22.5% of patients). Overall clinical response rate was 10% (4 partial responses); 26 patients (65%) had stable disease and 8 (20%) had disease progression. Median time to progression and median survival time were 90 and 187 days, respectively. One year survival rate was 13%. We conclude that carboplatin shows minimal toxicity with a discrete anti-tumor activity in patients with NSCLC and who are refractory to non-platinum combinations.

Activity of weekly irinotecan (CPT-11) in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes.

Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the treatment of non-small cell lung cancer (NSCLC). In this report we describe our experience with this drug when used as a single agent in patients with advanced NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous cell carcinoma) with a median age of 52 years (range 34-71) and a Karnofsky performance status of 60% (60-80%) were included in the study. At baseline, the patients had a median of two disease sites and had been treated with a median of two prior regimens. Irinotecan was given at a dose of 100 mg/m(2) i.v.) weekly for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were administered, and each patient received a median of 4 weeks of treatment (range 1-32). All patients were evaluated by intention-to-treat analysis for efficacy and safety. Main toxicities reported were grade 3 neutropenia (10% of patients), diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The overall clinical response rate was 16% (95% CI: 8-24) with three partial responses and 9 (47%) patients with stable disease. The median time to progression and the median survival time were 7 and 15 weeks, respectively. In conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in NSCLC patients refractory to platinum and taxanes.