Background Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease.

Methods In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group.

Results Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients who received interferon alone. Overall survival in the combination-therapy group did not differ significantly from that in the interferon group (hazard ratio, 0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the interferon group, the temsirolimus group, and the combination-therapy group were 7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia, and hyperlipidemia were more common in the temsirolimus group, whereas asthenia was more common in the interferon group. There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group (P=0.02).

Conclusions As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. (ClinicalTrials.gov number, NCT00065468 [ClinicalTrials.gov] .)

Source Information

From the Fox Chase Cancer Center, Philadelphia (G.H.); Sidney Kimmel Comprehensive Cancer Center, Baltimore (M.C.); Klinika Onkologii, Oddzial Chemioterapii, Pozna, Poland (P.T.); Our Lady of Mercy Medical Center, Bronx, NY (J.D.); University of California, Los Angeles, Los Angeles (R.F.); McMaster University, Hamilton, ON, Canada (A.K.); Lublin Oncological Center, Lublin, Poland (E.S.); Vanderbilt University Medical Center, Nashville (J.S.); Beth Israel Deaconess Medical Center, Boston (D.M.); National Institute of Oncology, Budapest, Hungary (I.B.); Military Medical Academy, Belgrade, Serbia (Z.K.); Regional Clinical Center of Urology and Nephrology, Kharkov, Ukraine (V.L.); University of Bonn, Bonn, Germany (I.G.H.S.-W.); Kemerovo State Medical Academy, Regional Clinical Hospital, Kemerovo, Russia (O.B.); Ege University Medical Faculty, Izmir, Turkey (E.G.); Wyeth Research, Cambridge, MA (T.O., S.L., L.M.); and Memorial Sloan-Kettering Cancer Center, New York (R.J.M.).

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