Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma

Purpose: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN alpha 2a) is superior to IFN alpha 2a alone in patients with advanced renal cell carcinoma (RCC). Patients and Methods: Two hundred eighty-four patients were randomized to treatment with IFN alpha 2a plus 13-CRA or treatment with IFN alpha 2a alone. IFN alpha 2a was given daily subcutaneously, starting at ct dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless greater than or equal to grade 2 toxicity occurred, in which case dose escalation was stopped. patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFN alpha 2a. Quality of life (QOL) was assessed. Results: Complete or partial responses were achieved by 12% of patients treated with IFN alpha 2a plus 13-CRA and 6% of patients treated with IFN alpha 2a (P = .14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P = .03). Nineteen percent of patients treated with IFN alpha 2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFN alpha 2a alone (P = .05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P = .26). QOL decreased during the first 8 weeks of treatment, and ct partial recovery followed. Lower scores were associated with the combination therapy. Conclusion: Response proportion and survival did not improve significantly with the addition of 13-CRA to IFN alpha 2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFN alpha 2a therapy in patients with IFN alpha 2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL. (C) 2000 by American Society of Clinical Oncology.