Abstract
Aims and background
A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rIL-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 ≥ 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m2 i.v. day 1 in alternating cycles; DTIC, 220 mg/m2 i.v. days 1, 2 and 3; CDDP, 25 mg/m2 i.v. days 1, 2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18 × 106 IU/m2/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha-interferon (IFN) s.c. 3 × 106 U day 12, 6 × 106 U day 14, 9 × 106 U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9 × 106 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); rIL-2, 0.65 (0.36-0.80); alpha-IFN, 0.01 (0-0.03); tamoxifen, 1.0. Systemic side effects of rIL-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.
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