A Randomized Phase 2 Trial of Bevacizumab with or without Daily Low-Dose Interferon Alfa-2b in Metastatic Malignant Melanoma |
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Authors: | Kimberly A Varker MD Jennifer E Biber BS Cheryl Kefauver RN Rhonda Jensen RN Amy Lehman BS Donn Young PhD Haifeng Wu MD Gregory B Lesinski PhD Kari Kendra MD PhD Helen X Chen MD Michael J Walker MD William E Carson III MD |
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Institution: | (1) Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, N924 Doan Hall, 410 W 10th Avenue, Columbus, Ohio 43210, USA;(2) Clinical Trials Office, The Ohio State University Comprehensive Cancer Center, A075 Starling Loving Hall, 320 W 10th Avenue, Columbus, Ohio 43210, USA;(3) Center for Biostatistics, The Ohio State University Comprehensive Cancer Center, M200 Starling Loving Hall, 320 W 20th Avenue, Columbus, Ohio 43210, USA;(4) Department of Pathology, The Ohio State University Comprehensive Cancer Center, 185A Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210, USA;(5) Division of Human Cancer Genetics, The Ohio State University Comprehensive Cancer Center, 302 Wiseman Hall, 400 W 12th Avenue, Columbus, Ohio 43210, USA;(6) Division of Hematology and Oncology, The Ohio State University Comprehensive Cancer Center, B415 Starling Loving Hall, 320 W 10th Avenue, Columbus, Ohio 43210, USA;(7) National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, Maryland, USA |
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Abstract: | Background Vascular endothelial growth factor (VEGF) is a proangiogenic molecule produced by melanoma cells. We hypothesized that administration
of bevacizumab (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa-2b (IFN-α2b), an inhibitor
of basic fibroblast growth factor (FGF), would lead to the regression of metastatic melanoma.
Methods Patients with metastatic melanoma were randomized to receive Bev (15 mg/kg intravenously every 2 weeks) with or without low-dose
IFN-α2b (1 MU/m2 subcutaneously daily). Patients exhibiting a clinical response or stable disease after 12 weeks were treated until disease
progression.
Results Thirty-two patients (16 per arm) were accrued (18 male, 14 female; mean age 57.5 years). Both regimens were well tolerated.
Six patients developed easily managed exacerbations of preexisting hypertension. Two patients developed grade 3 proteinuria
that resolved after a treatment break. IFN-α2b therapy was associated with grade 1 to 2 constitutional symptoms. Arterial
thromboembolic complications were observed in three patients (two mild myocardial infarctions, one transient ischemic attack),
all of whom had risk factors. One patient (Bev plus IFN-α2b arm) had locally recurrent scalp disease that partially responded
to therapy. Eight patients (five Bev, three Bev plus IFN-α2b) had prolonged disease stabilization (24 to 146 weeks). Plasma
levels of VEGF and FGF did not correlate with any clinical parameter. The patient with the longest period of stable disease
had the highest baseline VEGF and FGF.
Conclusions Bev was well tolerated at this dose and prolonged disease stabilization was achieved in one-quarter of metastatic melanoma
patients. Low-dose IFN-α2b did not augment the activity of Bev. |
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Keywords: | Bevacizumab Vascular endothelial growth factor (VEGF) Angiogenesis Interferon alfa-2b Metastatic melanoma Phase 2 clinical trial |
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