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Phase III Trial of Interferon Alfa-2a With or Without 13-cis-Retinoic Acid for Patients With Advanced Renal Cell Carcinoma

From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, and the Departments of Medical Imaging and Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center; Joan and Sanford I. Weill Medical College of Cornell University; and New York Presbyterian Hospital, New York, NY; Vanderbilt University, Nashville, TN; Indiana University, Indianapolis, IN; University of Wisconsin, Madison, WI; AMC Cancer Research Center, Denver, CO; and Evanston Northwestern Healthcare and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.

Address reprint requests to Robert J. Motzer, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.

PURPOSE: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN2a) is superior to IFN2a alone in patients with advanced renal cell carcinoma (RCC).

PATIENTS AND METHODS: Two hundred eighty-four patients were randomized to treatment with IFN2a plus 13-CRA or treatment with IFN2a alone. IFN2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless 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 IFN2a. Quality of life (QOL) was assessed.

RESULTS: Complete or partial responses were achieved by 12% of patients treated with IFN2a plus 13-CRA and 6% of patients treated with IFN2a (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 IFN2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFN2a 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 a 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 IFN2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFN2a therapy in patients with IFN2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.

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