Antonio C. Buzaid, MD

The results of treatment for metastatic melanoma remain disappointing.Single-agent chemotherapy produces response rates ranging from8% to 15%, and combination chemotherapy, from 10% to 30%. However,these responses are usually not durable. Immunotherapy, particularlyhigh-dose interleukin (IL)-2 (Proleukin), has also shown a lowresponse rate of approximately 15%, although it is often long-lasting.In fact, a small but finite cure rate of about 5% has been reported withhigh-dose IL-2. Phase II studies of the combination of cisplatin-basedchemotherapy with IL-2 and interferon-alfa, referred to as biochemotherapy,have shown overall response rates ranging from 40% to60%, with durable complete remissions in approximately 8% to 10% ofpatients. Although the results of the phase II single-institution studieswere encouraging, phase III multicenter studies have reported conflictingresults, which overall have been predominantly negative. Variousfactors probably explain these discrepancies including differentbiochemotherapy regimens, patient selection, and, most importantly,“physician selection.” Novel strategies are clearly needed, and the mostencouraging ones for the near future include high-dose IL-2 in combinationwith adoptive transfer of selected tumor-reactive T cells afternonmyeloablative regimens, BRAF inhibitors in combination with chemotherapy,and the combination of chemotherapeutic agents andbiochemotherapy with oblimersen sodium (Genasense).

The treatment of advanced cutaneous melanoma remains disappointing. Single-agent cytotoxic drugs usually produce response rates of less than 20%, though newer agents, particularly fotemustine and temozolomide, show some promise, especially in patients with brain metastases.