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.