Phase II studies of antiangiogenic four drug regimens for the treatment of advanced renal cell carcinoma: FUNIL-retinoid and the FUNIL-thalidomide protocols.

BACKGROUND AND PURPOSE: The objective of these studies was to determine the activity of two alternative 4- drug combinations using cis-retinoic acid or thalidomide administered with a previously developed combination of 5 fluorouracil, interferon-alpha, and interleukin 2 (FUNIL), for patients with metastatic renal cell carcinoma (RRC). METHODS: Patients enrolled in these studies had progressive measurable metastatic renal cell cancer and signed an informed consent. Treatments included continuous infusions of 5-fluorouracil, interferon-alpha, 6 MIU/m2 given subcutaneous on days 1, 3, and 5 every week, interleukin-2 6 MIU/m2/day given by continuous infusion days 2 to 5 every week, and either cis-retinoic acid at a dose of 1 mg/kg/day orally in two divided doses or thalidomide given at an initial dose of 200 mg per day. Each cycle consisted of 6 or 4 weeks of the combinations, respectively, followed by a 2-week rest. Patients were evaluated for response prior to each successive cycle. A 2-step mini-max statistical design was used. RESULTS: In the cis-retinoid study, 20 patients were enrolled. One patient was ineligible. There were 1 complete and 2 partial responses (one confirmed and one unconfirmed) (15.8%), 1 stable disease, and 15 disease progression. In the thalidomide combination study, 20 patients were enrolled, but only 19 are assessable. One patient progressed early and was never treated. There were 2 partial responses (10.5%), 4 stable disease, and 13 progressive disease. CONCLUSION: Neither the FUNIL-cis-retinoid nor the FUNIL-thalidomide regimens met their primary objective first step endpoint of 3 confirmed responses. Both regimens had significant adverse effects and neither is considered promising for further study.