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A Randomized Phase 2 Trial of Bevacizumab with or without Daily Low-Dose Interferon Alfa-2b in Metastatic Malignant Melanoma

  • Melanoma
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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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Acknowledgments

Supported by National Institutes of Health grants CA95426, P30 CA16058-28, P01 CA95426, K24 CA93670 (W.E.C.), and U01 CA-076576-06. K.A.V. is an NRSA T32 fellow (T32 CA09338-27).

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Authors and Affiliations

  1. Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, N924 Doan Hall, 410 W 10th Avenue, Columbus, Ohio, 43210, USA

    Kimberly A. Varker MD, Jennifer E. Biber BS, Michael J. Walker MD & William E. Carson III MD

  2. Clinical Trials Office, The Ohio State University Comprehensive Cancer Center, A075 Starling Loving Hall, 320 W 10th Avenue, Columbus, Ohio, 43210, USA

    Cheryl Kefauver RN & Rhonda Jensen RN

  3. Center for Biostatistics, The Ohio State University Comprehensive Cancer Center, M200 Starling Loving Hall, 320 W 20th Avenue, Columbus, Ohio, 43210, USA

    Amy Lehman BS & Donn Young PhD

  4. Department of Pathology, The Ohio State University Comprehensive Cancer Center, 185A Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio, 43210, USA

    Haifeng Wu MD

  5. Division of Human Cancer Genetics, The Ohio State University Comprehensive Cancer Center, 302 Wiseman Hall, 400 W 12th Avenue, Columbus, Ohio, 43210, USA

    Gregory B. Lesinski PhD

  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

    Kari Kendra MD, PhD

  7. National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, Maryland, USA

    Helen X. Chen MD

Authors
  1. Kimberly A. Varker MD
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  2. Jennifer E. Biber BS
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  7. Haifeng Wu MD
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  9. Kari Kendra MD, PhD
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  10. Helen X. Chen MD
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  11. Michael J. Walker MD
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  12. William E. Carson III MD
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Correspondence to William E. Carson III MD.

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Varker, K.A., Biber, J.E., Kefauver, C. et al. A Randomized Phase 2 Trial of Bevacizumab with or without Daily Low-Dose Interferon Alfa-2b in Metastatic Malignant Melanoma. Ann Surg Oncol 14, 2367–2376 (2007). https://doi.org/10.1245/s10434-007-9389-5

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  • DOI: https://doi.org/10.1245/s10434-007-9389-5

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