A phase 2 trial of bevacizumab and high-dose interferon alpha 2B in metastatic melanoma.
Author(s): Grignol VP, Olencki T, Relekar K, Taylor C, Kibler A, Kefauver C, Wei L, Walker MJ, Chen HX, Kendra K, Carson WE 3rd
Affiliation(s): Division of Surgical Oncology, The Ohio State University, Columbus, OH 43210, USA.
Publication date & source: 2011-07, J Immunother., 34(6):509-15.
Publication type: Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, N.I.H., Extramural
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 downregulate 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 5 MU/m subcutaneously during cycle 1 and was increased to 10 MU/m 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.