RESULTS OF INTERLEUKIN-2-BASED TREATMENT IN ADVANCED MELANOMA - A CASE RECORD-BASED ANALYSIS OF 631 PATIENTS

Purpose: In patients with stage IV melanoma, durable responses have be en reported with treatment regimens that involve high-dose interleukin -2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with inter feron alfa 2a or 2b (IFN alpha), or with cytotoxic drugs. Methods: Cas e records that contained pretreatment parameters, response data, and u pdated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox' s regression, respectively. Results: Patients were divided into four g roups according to treatment: IL-2 alone (n = 117), IL-2 and chemother apy (n = 49), IL-2 and IFN alpha (n = 153), and IL-2, chemotherapy, an d IFN alpha (n = 312). The median survival of all patients was 10.5 mo nths and the 2- and 5-year survival rates were 19.9% and 10.4%, respec tively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant fatter for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFN alpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious.Conclusion: Serum LDH, metastatic site, and performance status are useful stratification factors for randomize d trials in metastatic melanoma. The improved longterm survival rates observed in melanoma patients treated with IL-2/IFN alpha-containing r egimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias can not be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospe ctive randomized trials. J Clin Oncol 16:2921-2929. (C) 1998 by Americ an Society of Clinical Oncology.