A Pilot Study of Bevacizumab and Interferon-α2b in Ocular Melanoma

Abstract

Objectives We hypothesized that administration of bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, in combination with high-dose interferon-alpha2b (IFN-α2b), an inhibitor of basic fibroblast growth factor, would have clinical activity in patients with metastatic ocular melanoma. Methods Patients with metastatic ocular melanoma received bevacizumab (15 mg/kg intravenously every 2 weeks) plus IFN-α2b (5 MU/m2 subcutaneously 3 times weekly for 2 weeks followed by a dose of 10 MU/m2 subcutaneously thereafter). Patients exhibiting a clinical response or stabilization of disease were treated until disease progression. Results In this pilot study, 5 patients were treated (3 men, 2 women) with a mean age of 63.8 years (range, 53–71 years). Overall, the regimen was well-tolerated. The following adverse events were noted: grade 3 dyspnea (2 patients), grade 3 and 4 fatigue (2), grade 3 muscle weakness (1), grade 3 anorexia (1), grade 1 and 2 proteinuria (2), and grade 3 diarrhea (1). All adverse events resolved with a treatment holiday or dose reduction. One patient had reduction in tumor burden of 23% by Response Evaluation Criteria in Solid Tumors criteria and 2 patients had stabilization of disease lasting 28 and 36 weeks, respectively. Two patients failed to respond and progressed after 6 and 7 weeks of therapy. Conclusion Bevacizumab and IFN-α2b were well tolerated in this patient population, and clinical activity was observed. Further study of high-dose IFN-α2b in combination with bevacizumab in this setting is warranted.

Survival Rates in Patients After Treatment for Metastasis From Uveal Melanoma

“…[12][13][14] Theoretical advances in treatment included local administration (eg, hepatic artery perfusion and chemoembolization) of some of these same agents 15,16 and treatment with newer monoclonal antibodies. 17 The use of newer classes of drugs, such as methyl ethyl ketone (MEK) inhibitors, 18,19 programmed cell death protein-1 inhibitors, 20,21 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors, 22 has been tested over the past decade or more. None of these treatments has improved progression-free survival rates or overall survival in a meaningful way.…”

Phase II Trial of Sorafenib in Combination with Carboplatin and Paclitaxel in Patients with Metastatic Uveal Melanoma: SWOG S0512

“…This benefit mostly manifested as stabilization of disease (in contrast to the rapid-onset major tumor regressions seen with mutant-BRAF inhibitors in cutaneous melanoma [34]) raising the speculation that it may have been mediated by mechanisms other than inhibition of the MAPK-pathway. Indeed, there is increasing evidence of the importance of neo-angiogenesis in pathogenesis of uveal melanoma [35], [36], [37], [38] and it is plausible that the anti-angiogenic effects of sorafenib contributed to the disease stabilization and minor tumor responses observed in these patients.…”

Uveal melanoma: From diagnosis to treatment and the science in between

“…These studies will provide insight into the role of MEK inhibitors, their molecular targets, and other interacting pathways in the treatment of metastatic uveal melanoma. There have been several small phase 1 and 2 trials targeting pathways other than MAPK, such as gefitinib (an epidermal growth factor inhibitor), 97 thalidomide, 98 lenalidomide, 99 (immunomodulators), bevacizumab (a vascular endothelial growth factor [VEGF]-blocking antibody) plus interferon-a, 100 bevacizumab plus temozolomide, 101 aflibercept (a "decoy" receptor that binds circulating VEGF), 102 carboplatin/paclitaxel/sorafenib (a multikinase inhibitor), 82 imatinib (a KIT inhibitor), 103,104 and sunitinib (a multiple receptor tyrosine kinase inhibitor). 105 Unfortunately, none of these agents or combinations provided meaningful responses in patients with metastatic uveal melanoma.…”