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| |  Addition of Irinotecan to Cisplatin/Docetaxel Provides No Benefit in NSCLC, More Severe Toxicities: Presented at ASCO By Brian Hoyle CHICAGO -- June 6, 2010 -- The addition of irinotecan to a cisplatin/docetaxel combination did not improve the efficacy of the doublet chemotherapy on survival of patients with advanced non-small-cell lung cancer (NSCLC), researchers said here at the 2010 Annual Meeting of the American Society for Clinical Oncology (ASCO). Triple-combination treatment was also accompanied by increased severe toxicity. The findings reinforce the view that the triple-combo chemotherapy is not useful clinically. The findings of the randomised phase 3 study from the Okayama Lung Cancer Study Group were reported by Katsuyuki Kiura, MD, University Graduate School of Medicine, Okayama, Japan, during a poster presentation on June 5. The study was prompted by the authors' previous demonstration in a phase 2 trial that cisplatin plus docetaxel conferred a response rate of 57.1% and mean survival time (MST) of 17 months for previously untreated patients with advanced NSCLC. In an effort to improve these notable but "modest" benefits, a triple chemotherapy regimen incorporating irinotecan was pressed into service in the treatment of 25 patients with NSCLC and was evaluated in this phase 3 trial. As previously reported, response and survival were favourable in the 25 patients, toxicities, especially neutropenic fever, which occurred in over 50% of the patients, blunted enthusiasm over the triple-combination approach as a first-line treatment. The present results provide more substantive evidence. One hundred twenty patients with NSCLC who had not previously received chemotherapy were enrolled from 2004 to 2009 and randomised to receive cisplatin 60 mg/m2 (day 1), docetaxel 60 mg/m2 (day 1), and irinotecan 60 mg/m2 (day 2 and then every 3 weeks; n = 60) or double chemotherapy with cisplatin 80 mg/m2 and docetaxel 60 mg/m2 (day 1 and then every 3 weeks). The primary endpoint was overall survival (OS) and secondary endpoints included response rates, progression-free survival (PFS), and toxicity. Patients were treated for a median of 4 cycles. A beneficial response occurred with equal frequency in both treatment arms; at a median follow-up time of nearly 38 months, the MST was 12.1 months and the median PFS time was 4.2 months. Comparable objective responses were also noted in each arm concerning complete/partial responses, stable disease, and disease progression. However, consistent with the results from the aforementioned 25 patients, the benefit came at a cost for those patients receiving the triple therapy. The dose needed to be reduced for 52% of patients in triple-combination group, compared with 20% of patients in the double-combination group. Myelosuppression occurred as grade 3/4 neutropenia in 93% and 58% of patients in triple-combination and double-combination groups, respectively. Grade 3 neutropenia was evident in 53% and 18% of patients, respectively, with grade 4 neutropenia being equally prevalent (40%). The woes for the patients receiving the triple chemotherapy also included significantly increased prevalence of grade 3 or more diarrhoea (15% vs 3%; P = .016). OS data is forthcoming within the next year. The results reinforce the view that irinotecan inclusion in cisplatin plus docetaxel first-line chemotherapy for patients with advanced NSCLC is not a prudent option. Funding for this study was provided by sanofi-aventis. [Presentation title: A Randomized Phase III Study of Cisplatin and Docetaxel With or Without Irinotecan in Pts With Advanced Non-Small Cell Lung Cancer: Okayama Lung Cancer Study Group OLCSG 0403. Abstract 7584]
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