A MULTICENTER PHASE-II CLINICAL-TRIAL USING DACARBAZINE AND CONTINUOUS-INFUSION INTERLEUKIN-2 FOR METASTATIC MELANOMA - CLINICAL-DATA AND IMMUNOMONITORING

Background. Treatment of patients with metastatic melanoma with either dacarbazine or recombinant interleukin-2 (rIL-2) resulted in a respon se rate of approximately 15%. This study investigates the possible syn ergism of this chemoimmunotherapy combination. Methods. Fifty-seven pa tients with metastatic malignant melanoma received 135 treatment cycle s. Treatment consisted of dacarbazine (Days 1-5) at 250 mg/m(2) by a 3 0-minute slow infusion, and interleukin-2 by constant intravenous infu sion (Days 21-25 and 28-32) at 18 X 10(6) IU/m(2)/24 hours. After this treatment cycle, a 1-week rest was scheduled, and in the absence of u ndue toxicity or tumor progression, patients received a second cycle a s described. Maximum treatment consisted of two induction and four mai ntenance cycles. In a subgroup of patients, immunoparameters were anal yzed to identify prognostic factors. Standard supportive care was give n. Results. Common toxicities included fever, hypotension, nausea/vomi ting, anemia, leukopenia, thrombocytopenia, an increase in serum lacti c dehydrogenase levels and diarrhea. The objective response rate was 1 5.8% (one complete response and eight partial responses). In 14 patien ts, the disease stabilized. For patients who had an objective response , median response duration was 13.9 months (6.3-39.0(+)), and median s urvival was 19.0 months (6.3-39.0(+)); overall survival was 9.3 months (0.8-39.0(+)). Immunomonitoring did not reveal any relevant prognosti c factors for overall response. Conclusions. Sequential treatment with dacarbazine and rIL-2 is feasible and produces long-lasting responses in a minority of patients.