Pros and cons of adjuvant interferon in the treatment of melanoma

Should interferon alpha (IFN-alpha) be considered the standard of care for the adjuvant therapy of high-risk malignant melanoma? For 2003, it was estimated that 51,400 cases of invasive melanoma would be diagnosed. The risk of recurrence after surgery is reported to be approximately 60% for patients with thick primary lesions (T4N0M0, American Joint Committee on Cancer [AJCC] stage IIB) and 75% for patients with regional nodal metastases (TI-4N1M0, AJCC stage III). The observation that melanoma is susceptible to attack by the host's immune system has resulted in the testing of a remarkably broad spectrum of immunotherapies in the adjuvant setting. Many of these approaches failed to demonstrate a significant clinical impact, until the use of adjuvant IFN-alpha. Conflicting data from several large, randomized clinical trials resulted in a rapid rise and then decline in the use of IFN-alpha in the adjuvant setting. This roller coaster has left many clinicians still hesitant to strongly recommend it, and the use of adjuvant IFN-alpha in high-risk melanoma remains controversial. This manuscript reviews the leading arguments for and against its routine use and addresses questions regarding its role in the management of high-risk malignant melanoma.