Annals of Surgical Oncology

, Volume 14, Issue 8, pp 2367–2376

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

  • Kimberly A. Varker
  • Jennifer E. Biber
  • Cheryl Kefauver
  • Rhonda Jensen
  • Amy Lehman
  • Donn Young
  • Haifeng Wu
  • Gregory B. Lesinski
  • Kari Kendra
  • Helen X. Chen
  • Michael J. Walker
  • William E. Carson III
Melanoma

DOI: 10.1245/s10434-007-9389-5

Cite this article as:
Varker, K.A., Biber, J.E., Kefauver, C. et al. Ann Surg Oncol (2007) 14: 2367. doi:10.1245/s10434-007-9389-5

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.

Keywords

Bevacizumab Vascular endothelial growth factor (VEGF) Angiogenesis Interferon alfa-2b Metastatic melanoma Phase 2 clinical trial 

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Kimberly A. Varker
    • 1
  • Jennifer E. Biber
    • 1
  • Cheryl Kefauver
    • 2
  • Rhonda Jensen
    • 2
  • Amy Lehman
    • 3
  • Donn Young
    • 3
  • Haifeng Wu
    • 4
  • Gregory B. Lesinski
    • 5
  • Kari Kendra
    • 6
  • Helen X. Chen
    • 7
  • Michael J. Walker
    • 1
  • William E. Carson III
    • 1
  1. 1.Division of Surgical OncologyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  2. 2.Clinical Trials OfficeThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  3. 3.Center for BiostatisticsThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  4. 4.Department of PathologyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  5. 5.Division of Human Cancer GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  6. 6.Division of Hematology and OncologyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  7. 7.National Cancer InstituteCancer Therapy Evaluation ProgramBethesdaUSA