THE FEASIBILITY OF REPETITIVE COURSES OF HIGH-DOSE CONTINUOUS INTRAVENOUS-INFUSION INTERLEUKIN-2 AND SUBCUTANEOUS ALPHA-INTERFERON WITH POLYCHEMOTHERAPY IN ADVANCED MALIGNANT-MELANOMA

Aims and background: A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rlL-2) and subcutaneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficaciuous way to sequence this kind of treatment for advanced malignant melanoma. Study design: Patients who had measurable metastatic melanoma, a Karnofsky performance status greater than or equal to 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m(2) i.v. day 1 in alternating cycles; DTIC, 220 mg/m(2) i.v. days 1, 2 and 3; CDDP, 25 mg/m(2) i.v. days 1,2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18x10(6) IU/m(2)/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha-interferon (IFN) s.c. 3x10(6) U day 12, 6x10(6) U day 14, 9x10(6) U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9x10(6) U days 2, 5, 7, 9, 12, 14, 16, 19, 21, 23, 26, and 28). Two consecutive cycles were planned until response evaluation. Results: Three patients were treated according with the protocol; none of them was able to respect the planned dose-intensity schedule. The given dose intensity/planned dose intensity ratios were as follows: DTIC, 0.74 (range, 0.70-0.80); CDDP, 0.77 (0.72-0.80); BCNU, 0.77 (0.72-0.80); rlL-2, 0.65 (0.36-0.80); alpha-IFN, 0.01 (0-0.03); tameoxifen, 1.0. Systemic side effects of rlL-2 and myelotoxicity were the main reasons for treatment delay and/or dose-reduction, and for the long period of hospital care. Conclusions: We conclude that the treatment schedule is not feasible. However, since we believe that combined chemo-immunotherapy is a potentially active treatment in metastatic malignant melanoma, we have modified it in order to make it more feasible and consequently efficacious.