Search

Background The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC). Patients and methods In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rIL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 106 IU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-α at a daily dose of 6 x 106 IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity. Results Twenty-three percent (95% CI: ± 17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI: ± 11.9) and 9% (95% CI: ± 11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine, months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN. Conclusions Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.

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.