Phase II trial of irinotecan, carboplatin, and bevacizumab in the treatment of patients with extensive-stage small-cell lung cancer.

INTRODUCTION: Bevacizumab's role in the treatment of small cell lung cancer (SCLC) is unknown. A multicenter phase II trial with bevacizumab plus chemotherapy was conducted in patients with untreated extensive-stage SCLC.

METHODS: Eligibility: no prior SCLC chemotherapy, no active brain metastases, no hemoptysis, and Eastern Cooperative Oncology Group performance status 0-1. Treatment consisted of irinotecan (60 mg/m2) administered intravenously (IV) on days 1, 8, 15; carboplatin area under the concentration-time curve = 4, IV, on day 1; bevacizumab (10 mg/kg, IV) on days 1 and 15 every 28 days for up to six cycles. Restaging was performed every two cycles (8 weeks). Patients with no progression received maintenance bevacizumab. Primary end point is 40% improvement in historical median time to progression (TTP) of 6 months.

RESULTS: Fifty-one patients were enrolled from February 2006 to March 2007 (22-month median follow-up). Baseline features: median age 66 years (range 46-81 years); male 57%; and Eastern Cooperative Oncology Group performance status 0-1 33/67%. Objective response rate 84% (95% CI 71-93%): 1 complete and 42 partial responses. Two patients (4%) had stable disease, and two patients had progressive disease. Four patients were unassessable because of treatment-related toxicity. Median TTP was 9.13 months (95% CI 7.36-9.46 months). Median overall survival was 12.1 months (95% CI 9.6-13.5 months); 1- and 2-year overall survivals were 51 and 14%, respectively. Grade 3/4 toxicity (> or = 10%): neutropenia (39%), thrombocytopenia (22%), dehydration (10%), diarrhea (31%), fatigue (20%), and pulmonary symptoms (10%). No significant bleeding occurred.

CONCLUSIONS: In this phase II trial, irinotecan, carboplatin, and bevacizumab achieved response, TTP, and survival outcomes that compare favorably with larger randomized trials using chemotherapy alone. Randomized trials can best assess bevacizumab's impact in the first-line treatment of extensive-stage SCLC.