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Previous Volume 338:1265-1271 April 30, 1998 Number 18 Next

	Full Text PDF Editorial by Young, R. C. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective 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 interferon gamma-1b or placebo.

Methods Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 µg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses 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-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced 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 metastatic 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 events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall 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 difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P = 0.52).

Conclusions No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Source Information

From the Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver (M.E.G.); McGill University, Montreal (M.E.); Laval University, Quebec City, Que. (Y.F.); McMaster University, Hamilton, Ont. (I.D.); Cross Cancer Centre, Edmonton, Alta. (P.V.); University of Montreal, Montreal (F.S.); Sunnybrook Medical Centre, University of Toronto, Toronto (L.H.K.); and Princess Margaret Hospital, Toronto (M.J.M.) — all in Canada; and Genentech, San Francisco (V.P., A.B.). Other authors were David Bell (Queen Elizabeth Health Science Center, Dalhousie University, Halifax, N.S.), Scott Ernst (Tom Baker Cancer Center, Calgary, Alta.), Ernest Ramsey (Health Sciences Center, University of Manitoba, Winnipeg), Joe Chin (London Health Sciences Center, University of Western Ontario, London), Alvaro Morales (Queens University, Kingston, Ont.), Heidi Martins (British Columbia Cancer Agency, Victoria), and Coree Sanders (Genentech, San Francisco).

Address reprint requests to Dr. Gleave at the Division of Urology, Vancouver Hospital and Health Sciences Centre, D-9 Heather Pavilion, Vancouver, BC V5Z 3J5, Canada.

Full Text of this Article

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Extract | Full Text  
N Engl J Med 1998; 339:849-851, Sep 17, 1998. Correspondence

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