Phase II study of gemcitabine and carboplatin plus bevacizumab for stage III/IV non-small cell lung cancer: Preliminary safety data

Abstract

17091 Background: The current standard of care for stage III/IV non-small cell lung cancer (NSCLC) is platinum-based chemotherapy. Bevacizumab (BV) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that improves survival when used in combination with chemotherapy. In a randomized, phase II study of patients (pts) with advanced NSCLC, the addition of bevacizumab 15 mg/kg to paclitaxel/carboplatin (PC) resulted in prolonged survival and progression-free survival compared with PC alone (Sandler AB et al, ASCO 2005). In the present study, we are using BV 15 mg/kg in combination with gemcitabine/carboplatin (GC) for the treatment of NSCLC. Preliminary safety findings are summarized. Methods: Eligible pts with stage IV NSCLC, PS 0–1, and adequate hematologic, renal and hepatic function, were enrolled; pts with squamous cell carcinoma, tumor in the central airways, baseline hemoptysis, or brain metastases were excluded. GC/BV treatment was given in q 3-weekly cycles for 6 cycles, with BV continued in stable and responding patients. G 1250 mg/m2 was given on days 1 and 8 and C AUC 5 was given on day 1. BV 15 mg/kg was given on day 1. After 7 pts were enrolled, the study was amended to reduce the dose of G to 1000 mg/m2 on days 1 and 8 due to unacceptable neutropenia. Primary endpoint of the study is time to progression. Results: To date, 9 pts have received treatment; we report here the hematologic toxicity of the first 8, and non-hematologic toxicity of the first 7. There are 6 men and 2 women, median age 61.5 years. There was one episode of grade 4 thrombocytopenia, and Grade 3 events have been reported a number of patients: leukopenia (5 pts); neutropenia (4 pts); thrombocytopenia (4 pts); infection (1 pt); hemoglobin toxicity (1 pt); fatigue (1 pt); diarrhea (1 pt); dyspnea (1 pt); and dehydration (1 pt). Adverse events possible related to BV include Grade 3 hypertension (1 pt) and Grade 1 epistaxis (2 pts). No thrombosis or proteinuria has been reported. There have been no fatal toxicities. Conclusions: To date, the addition of BV to GC in pts with NSCLC is generally well tolerated and no unexpected adverse events possibly related to BV were observed. Enrollment is ongoing. [Table: see text]