RESUMO
Interferon-α-2a (IFNa) has proven antitumor activity in a variety of neoplastic diseases, but no clear modality of administration has been validated. The aim of our study was to estimate the optimal dose of continuous subcutaneous administration of IFNa in stage IV metastatic melanoma patients. An innovative dose-finding approach, combining phase I and phase II trials, was planned to evaluate the toxicity and efficacy of four dose levels of IFNa (3, 6, 9, and 12 MIU/day). Sixteen patients were enrolled in this study. Three patients were treated according to the dose-allocation rule with IFNa at 3 MIU/day, nine patients at 6 MIU/day, and four patients at 9 MIU/day. Dose-limiting toxicities were grade 3 in five patients (three at a dose level of 6 MIU/day and two at a dose level of 9 MIU/day). Four clinically relevant responses were obtained, one at dose level 3 MIU/day, one at a dose level of 6 MIU/day, and two at a dose level of 9 MIU/day. The three final responses, at dose levels of 6 and 9 MIU/day, were associated with a dose-limiting toxicity. A dose level of 6 MIU/day was well tolerated but did not reach the desired efficacy target of 20%, and a dose level of 9 MIU/day was estimated to be too toxic. This original dose-finding methodology made it possible to estimate the rate of toxicity and efficacy in a small sample of patients without toxicity associated with each dose level.
