Is there a role for adjuvant high-dose interferon-alpha-2b in the management of melanoma?
The knowledge that melanoma is susceptible to attack by the host's immune system has resulted in the testing of a variety of immunotherapies. Interferon-alpha-2b, which has several anti-tumour mechanisms including an antiproliferative effect, an anti-angiogenesis effect, the enhancement of natural-killer cell activity and the upregulation of tumour antigen presentation, has shown tremendous potential. Early trials using low-dose and intermediate-dose regimens demonstrated no benefit to survival. However, the Eastern Cooperative Oncology Group trial EST 1684, showed that a high-dose regimen involving an induction phase of intravenous interferon-alpha-2b 20 MU/m(2) 5 days a week for 4 weeks, followed by a maintenance phase of subcutaneous 10 MU/m(2) 3 days a week for the remainder of a year, led to significant improvements in both disease-free and overall survival compared with observation. On the basis of these results, the US FDA approved high-dose interferon-alpha-2b for the post-surgical adjuvant therapy of high-risk melanoma. Unfortunately, the results of subsequent trials involving high-dose interferon-alpha-2b have not been as clear, and its role in the adjuvant treatment of melanoma remains controversial. Concerns remain regarding the design and interpretation of the clinical trials, the cost and toxicity of treatment, and the appropriate selection of patients who should be treated. This article reviews the existing data and attempt to address the arguments for and against a role for adjuvant high-dose interferon-alpha-2b in the management of melanoma.
Sabel
Michael S
MS
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA. msabel@umich.edu
Sondak
Vernon K
VK
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins