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Motzer RJ , Hudes GR , Curti BD , McDermott DF , Escudier BJ , Negrier S , Duclos B , Moore L , O'Toole T , Boni JP , Dutcher JP
Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma
Journal of Clinical Oncology. 2007 Sep;25(25) :3958-3964
AbstractPurpose Temsirolimus, an inhibitor of the mammalian target of rapamycin, has single- agent activity against advanced renal cell carcinoma ( RCC). A recommended dose and safety profile for the combination of temsirolimus and interferon alfa ( IFN) were determined in patients with advanced RCC. Patients and Methods Patients were enrolled onto a multicenter, ascending- dose study of temsirolimus ( 5, 10, 15, 20, or 25 mg) administered intravenously once a week combined with IFN ( 6 or 9 million units [ MU]) administered subcutaneously three times per week. An expanded cohort was treated at the recommended dose to obtain additional safety and efficacy information. Results Seventy-one patients were entered to receive one of six dose levels. The recommended dose was temsirolimus 15 mg/ IFN 6 MU based on dose- limiting toxicities of stomatitis, fatigue, and nausea/ vomiting, which were observed at higher doses of temsirolimus and IFN. The most frequent grade 3 or 4 toxicities occurring in any cycle included leukopenia, hypophosphatemia, asthenia, anemia, and hypertriglyceridemia for all patients and those who received the recommended dose. Among patients who received the recommended dose ( n = 39), 8% achieved partial response and 36% had stable disease for at least 24 weeks. Median progression-free survival for all patients in the study was 9.1 months. Conclusion The combination of temsirolimus and IFN has an acceptable safety profile and displays antitumor activity in patients with advanced RCC. Temsirolimus 15 mg plus IFN 6 MU is the recommended dose for evaluation in a randomized phase III study.
NotesISI Document Delivery No.: 209VL Times Cited: 0 Cited Reference Count: 31 Cited References: ATKINS MB, 2004, J CLIN ONCOL, V22, P909 BJORNSTI MA, 2004, NAT REV CANCER, V4, P335 BONI JP, 2005, CLIN PHARMACOL THER, V77, P76 CHAN S, 2005, J CLIN ONCOL, V23, P5314 CHANG SM, 2005, INVEST NEW DRUG, V23, P357 COHEN HT, 2005, NEW ENGL J MED, V353, P2477 DELBUFALO D, 2006, CANCER RES, V66, P5549 DEMULDER PHM, 1995, BRIT J CANCER, V71, P371 DUTCHER JP, 2003, P AN M AM SOC CLIN, V22, P213 GALANIS E, 2005, J CLIN ONCOL, V23, P5294 GIBBONS JJ, 2006, RPT49843 HIDALGO M, 2006, CLIN CANCER RES, V12, P5755 HUDES G, 2006, J CLIN ONCOL S 1, V24, S2 JUSKO WJ, 1992, APPL PHARMACOKINETIC MOTZER RJ, 2000, J CLIN ONCOL, V18, P2972 MOTZER RJ, 2002, J CLIN ONCOL, V20, P289 MOTZER RJ, 2004, J CLIN ONCOL, V22, P454 MOTZER RJ, 2006, J CLIN ONCOL, V24, P16 PANTUCK AJ, 2003, CLIN CANCER RES, V9, P4641 PATEL PH, 2006, BRIT J CANCER, V94, P614 PERALBA JM, 2003, CLIN CANCER RES, V9, P2887 PODSYPANINA K, 2001, P NATL ACAD SCI USA, V98, P10320 PUNT CJA, 2003, ANN ONCOL, V14, P931 RATAIN MJ, 2006, J CLIN ONCOL, V24, P2505 RAYMOND E, 2004, J CLIN ONCOL, V22, P2336 RITCHIE A, 1999, LANCET, V353, P14 SHI YJ, 2002, CANCER RES, V62, P5027 SMITH JW, 2004, J CLIN ONCOL S, V22, S385 THERASSE P, 2000, J NATL CANCER I, V92, P205 THOMAS GV, 2006, NAT MED, V12, P122 WITZIG TE, 2005, J CLIN ONCOL, V23, P5347