SUBCUTANEOUS LOW-DOSE INTERLEUKIN-2 PLUS ALPHA-INTERFERON IN ADVANCEDMALIGNANT-MELANOMA

Aims and Background: Interferon (IFN) and interleukin-2 (IL-2) have be en 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 s ubcutaneous administration of low-dose IL-2 was found to be a well-tol erated and effective treatment for renal cancer. Since the combination of low doses of IL-2 and IFN has been hypothesized to have synergisti c biologic and cytotoxic effects, we evaluated feasibility and patient compliance of a scheme that combined recombinant IFN-alpha (rIFN-alph a) (3 million units by intramuscular injection, 3 times a week) plus l ow-dose IL-2 (9 million IU, 3 to 5 times a week) administered subcutan eously for 2 weeks every 28 days. Results: Fifteen patients with disse minated malignant melanoma previously treated with chemotherapy entere d 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 cy cles. Mild hematologic toxicity (grade 2) was observed at the highest weekly dose of IL-2. No major responses were observed in this subset o f heavily pretreated patients. Conclusions: We conclude that the regim en studied is feasible and well tolerated in an out-patient setting, b ut it is unlikely to be effective. The good patient compliance makes t his schedule eligible to evaluate whether IL-2 plus rIFN-alpha can enh ance the results of chemotherapy in this disease.