RISK AND OUTCOME IN METASTATIC MALIGNANT-MELANOMA PATIENTS RECEIVING DTIC, CISPLATIN, BCNU AND TAMOXIFEN FOLLOWED BY IMMUNOTHERAPY WITH INTERLEUKIN-2 AND INTERFERON ALPHA2A

Combined chemo-/immunotherapy has shown high objective response rates and a significant though small proportion of longterm complete respond ers in metastatic malignant melanoma. The purpose of this study was to determine response rates, freedom from treatment failure (FFTF) and o verall survival in patients with advanced metastatic malignant melanom a treated with combined chemo-/ immunotherapy, and to determine the va lue of a prognostic model for prediction of treatment outcome, FFTF an d survival. Sixty-nine patients with metastatic malignant melanoma rec eived combined chemo-/immunotherapy consisting of up to four cycles of DTIC (220 mg m(-2) i.v, days 1-3), cisplatin (35 mg m(-2) i.v. days 1 -3), BCNU (150 mg m(-2) i.v. day 1, cycles 1 and 3 only) and tamoxifen (20 mg orally, daily). Two cycles of chemotherapy were followed by 6 weeks of outpatient immunotherapy with combined interleukin 2 (20 x 10 (6) IU m(-2) days 3-5, weeks 1 and 4; 5 x 10(6) IU m(-2) days 1, 3, 5, weeks 2, 3, 5, 6) and interferon-alpha (6 x 10(6) IU m(-2) s.c. day 1 , weeks 1 and 4; days 1, 3, 5, weeks 2, 3, 5, 6). All patients were ev aluated on an intention-to-treat basis. Of 69 patients entered in the study, seven achieved complete remissions and 20 reached partial remis sions with an objective response rate of 39% (95% confidence interval 28-52%). Median survival was 11 months, median FFTF was 5 months. Seve n patients achieved ongoing long-term remissions, with maximum surviva l of 58 + months, and maximum FFTF of 58 + months. By Kaplan-Meier sur vival analysis and two-proportional Cox regression analysis, pretreatm ent performance status and serum lactic dehydrogenase were statistical ly significant and independent predictors of survival; risk groups cou ld be defined as (a) the absence of both or (b) the presence of either one or both of these risk factors. Whereas survival and response were significantly influenced by patient risk, no infuence could be demons trated for FFTF. This combined outpatient chemo-/immunotherapy is feas ible and results in objective response rates and survival similar to e arlier trials. Pretreatment risk, as defined by serum lactate dehydrog enase (LDH) and performance status, has a significant impact on treatm ent outcome and patient survival.