Subcutaneous interleukin-2 and interferon-alpha plus cisplatin with and without prophylactic cimetidine in patients with metastatic malignant melanoma: a phase II study

A phase II study was performed to evaluate the efficacy of cisplatin combin ed with interleukin-2 and interferon-alpha 2b administered subcutaneously t o patients with metastatic malignant melanoma (MMM), Between April 1994 and January 1999, 87 patients with MMM and a WHO performance status of less th an or equal to 2 were entered into the study. The first 42 patients had pro phylactic cimetidine; the other 45 patients did not. An overall response ra te of 27% was achieved in the 82 patients evaluable for response. The media n response duration was 7.0 months (range 4.4-29.0 months). The median surv ival for all patients was 10.1 months (range 0.4-64.9+ months). Toxicity wa s substantial but generally manageable and usually reversed on dose reducti on or temporary interruption of treatment. Two patients (2%) died of treatm ent-related toxicity. No difference in response or survival was seen in the patients treated with or without cimetidine, In multivariate analysis, lac tate dehydrogenase level (P<0.001), number of metastatic sites (P=0.014) an d performance status (P=0.035) was shown to be independent prognostic facto rs for survival. This high dose interleukin-2 subcutaneous regimen resulted in a small fraction of long-term survivors. The response and survival resu lts were not superior to other studies using lower and less toxic interleuk in-2 doses. (C) 2000 Lippincott Williams & Wilkins.