Sequential chemotherapy with combination irinotecan and cisplatin followed by docetaxel for treatment-naïve patients with advanced non-small cell lung cancer.
ABSTRACT Sequential administration of platinum-based doublet therapy and then a taxane may reduce the risk of drug resistance and, therefore, improve treatment outcome. This study was designed to evaluate the efficacy and tolerability of sequential administration of irinotecan and cisplatin and then docetaxel in patients with advanced non-small cell lung cancer (NSCLC).
Eligible patients received irinotecan in 60-mg/m2 infusions for 30 to 60 minutes on days 1, 8, and 15, and cisplatin in 75-mg/m2 infusions for 60 minutes on day 1 every 28 days for four cycles (IC). Regardless of the response, patients received up to four cycles of sequential docetaxel in 75-mg/m2 infusions for 60 minutes.
Forty-six patients with histologically confirmed chemotherapy-naïve stage IIIB or IV NSCLC were enrolled, of whom 42 were evaluable. The response rate at completion of chemotherapy with IC was 45.2% (95% confidence interval [CI]: 30.2%-60.3%). Five patients had improvement of disease status during sequential docetaxel, and seven patients had disease progression. Progression-free survival was 8.0 months (95% CI: 5.4-9.9 months), and the overall median survival was 14.6 months (95% CI: 9.8-17.9 months). The 1-, 2-, and 3-year survival rates were 54.3%, 22.6%, and 12.1%, respectively. The incidence of severe (> or =CTC V2 grade 3) neutropenia during IC was 23.9% compared with 95.7% for sequential docetaxel (p < 0.0001).
Sequential administration of IC and then docetaxel is feasible and is associated with a prolonged progression-free survival, but the current data do not confirm an improvement in treatment outcome by the sequential approach.
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ABSTRACT: BACKGROUND: Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC. METHODS: Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m(2). RESULTS: In total, 46 patients were included. Median age was 59.6 years (range 41.3-74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin-gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin-gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity. CONCLUSION: Sequential chemotherapy with carboplatin-gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.International Journal of Clinical Oncology 09/2012; · 1.41 Impact Factor