Current therapy for malignant melanoma.

Abstract

The majority of patients with stage I melanoma can be cured with surgery. Extension of tumor to the regional lymph nodes portends a poor prognosis, with an expected 5-year survival rate of no more than 20% to 25%. Adjuvant therapy has not been particularly useful in such patients. Patients with metastatic melanoma generally do poorly and have a median survival of 4 to 6 months. Such patients are treated with systemic therapy unless they have a surgically resectable single site of metastasis, in which case surgical resection offers the best palliation. The chemotherapeutic agent that is most widely used is dacarbazine (DTIC), which has been in use for the past 20 years. When used as a single agent, DTIC has produced response rates of 15% to 20%. These responses largely occur in soft-tissue disease and last an average of 3 to 6 months. Complete remissions occur in fewer than 5% of patients. In addition to DTIC, other drugs with significant activity against metastatic melanoma are the nitrosoureas, the vinca alkaloids, and cisplatin. Combinations of DTIC and nitrosoureas have not resulted in significant improvement in the response rate, which has generally been 20% to 25%. During the past decade, several triple-drug combinations have been tested, with some evidence of an increase in the response rate to 25% to 30%. More recently developed combinations incorporating cisplatin and the vinca alkaloids in conjunction with DTIC have yielded response rates of 30% to 40%. Because most of these reports are pilot studies and have not been tested in controlled trials, the evidence of the superiority of these combined regimens over DTIC alone cannot be considered conclusive. Combination chemotherapy regimens do produce slightly higher complete response rates of approximately 10%, and the duration of responses is somewhat longer (6 to 9 months). During the past 5 years, biologic therapy with interferons and interleukin-2 (IL-2) has shown clinical evidence of activity against metastatic melanoma. The recombinant alpha interferons (alfa-2a and alfa-2b) have been widely used and have induced tumor regressions in 15% to 20% of patients. Because the activity of interferons is not compromised by prior chemotherapy, their use is more popular as second-line therapy, with an expected overall response rate of 15%. Other studies have utilized interferon in untreated patients, where the response rate may be slightly higher.(ABSTRACT TRUNCATED AT 400 WORDS)