Subcutaneous low-dose interleukin-2 plus alpha interferon in advanced malignant melanoma

Aims and Background: Interferon (IFN) and interleukin-2 (IL-2) have been proven to be active agents in the treatment of malignant melanoma, but the most effective doses of these cytokines were often associated to important side effects and poor patient compliance. Recently, the subcutaneous administration of low-dose IL-2 was found to be a well-tolerated and effective treatment for renal cancer. Since the combination of low doses of IL-2 and IFN has been hypothesized to have synergistic biologic and cytotoxic effects, we evaluated feasibility and patient compliance of a scheme that combined recombinant IFN-alpha (rIFN-alpha) (3 million units by intramuscular injection, 3 times a week) plus low-dose IL-2 (9 million IU, 3 to 5 times a week) administered subcutaneously for 2 weeks every 28 days. Results: Fifteen patients with disseminated malignant melanoma previously treated with chemotherapy entered the study. All but the first 2 self-administered the therapy at home and were followed in an out-patient setting. None of them required in-patient care for toxicity. No WHO grade 4 side effects were detected; the only grade 3 side effects were fever and asthenia in 5% of the cycles. Mild hematologic toxicity (grade 2) was observed at the highest weekly dose of IL-2. No major responses were observed in this subset of heavily pretreated patients. Conclusions: We conclude that the regimen studied is feasible and well tolerated in an out-patient setting, but it is unlikely to be effective. The good patient compliance makes this schedule eligible to evaluate whether IL-2 plus rIFN-alpha can enhance the results of chemotherapy in this disease.