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 chemothe rapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (contin uous intravenous infusion recombinant interleukin-2 (rlL-2) and subcut aneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficaciuous way to sequence this kind of treatme nt for advanced malignant melanoma. Study design: Patients who had mea surable metastatic melanoma, a Karnofsky performance status greater th an or equal to 80, and no clinically significant hematologic or cardia c disfunction were considered eligible. Treatment consisted of BCNU, 1 50 mg/m(2) i.v. day 1 in alternating cycles; DTIC, 220 mg/m(2) i.v. da ys 1, 2 and 3; CDDP, 25 mg/m(2) i.v. days 1,2 and 3; tamoxifen 10 mg t wice/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, 2 1, 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 r esponse evaluation. Results: Three patients were treated according wit h the protocol; none of them was able to respect the planned dose-inte nsity 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 myelotoxic ity were the main reasons for treatment delay and/or dose-reduction, a nd for the long period of hospital care. Conclusions: We conclude that the treatment schedule is not feasible. However, since we believe tha t combined chemo-immunotherapy is a potentially active treatment in me tastatic malignant melanoma, we have modified it in order to make it m ore feasible and consequently efficacious.