INTERFERON GAMMA-1B COMPARED WITH PLACEBO IN METASTATIC RENAL-CELL CARCINOMA

Background Most trials of immunomodulators in metastatic renal-cell ca rcinoma have been uncontrolled and subject to selection bias. The obje ctive of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human i nterferon gamma-1b or placebo. Methods Patients with biopsy-proved met astatic renal-cell carcinoma were randomly assigned to receive interfe ron gamma-1b (60 mu g per square meter of body-surface area subcutaneo usly once weekly) or placebo. The primary tumor had been treated by ne phrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all respon ses were independently reviewed by a committee that was unaware of the treatment. Results A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-o ne patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well ba lanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more meta static sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively , of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related ev ents were rare, occurring in 1 percent of patients in the interferon g roup. No significant differences between groups were observed in overa ll response rates, time to disease progression, or survival. The overa ll response rate was 4.4 percent (3.3 percent complete response and 1. 1 percent partial response) in the interferon group and 6.6 percent (3 .3 percent complete response and 3.3 percent partial response) in the placebo group (P = 0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1 .9 months in both groups (P = 0.49), and there was no significant diff erence in median survival (12.2 months with interferon vs. 15.7 months with placebo, P = 0.52). Conclusions No difference in outcome was obs erved in patients with metastatic renal-cell carcinoma who were treate d with interferon gamma-1b as compared with placebo. These results emp hasize the necessity of testing the efficacy of immunomodulators in ra ndomized studies. (C)1998, Massachusetts Medical Society.