期刊
JOURNAL OF IMMUNOTHERAPY
卷 34, 期 6, 页码 509-515出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e31821dcefd
关键词
bevacizumab; vascular endothelial growth factor; angiogenesis; interferon alpha 2b; metastatic melanoma; phase 2 clinical trial
资金
- NIH [U01 CA76576, P01 CA095426, P30 CA16058, PPG 6001409, T32 CA009338, K24 CA093670, N01CM62207]
- Genentech
Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-alpha) has antiangiogenic properties through its ability to down-regulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-alpha was administered thrice weekly at 5MU/m(2) subcutaneously during cycle 1 and was increased to 10MU/m(2) during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-alpha dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-alpha included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P = 0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.
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