PURPOSE: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. PATIENTS AND METHODS: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. RESULTS:A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04). CONCLUSION: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.
RCT Entities:
PURPOSE: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. PATIENTS AND METHODS: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. RESULTS: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04). CONCLUSION: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.
Authors: D R Parkinson; J S Abrams; P H Wiernik; A A Rayner; K A Margolin; D A Van Echo; M Sznol; J P Dutcher; F R Aronson; J H Doroshow Journal: J Clin Oncol Date: 1990-10 Impact factor: 44.544
Authors: J C Yang; S L Topalian; D Parkinson; D J Schwartzentruber; J S Weber; S E Ettinghausen; D E White; S M Steinberg; D J Cole; H I Kim Journal: J Clin Oncol Date: 1994-08 Impact factor: 44.544
Authors: J Atzpodien; A Körfer; P Evers; C R Franks; J Knüver-Hopf; E Lopez-Hänninen; M Fischer; H Mohr; I Dallmann; M Hadam Journal: Mol Biother Date: 1990-03
Authors: S A Rosenberg; M T Lotze; L M Muul; S Leitman; A E Chang; S E Ettinghausen; Y L Matory; J M Skibber; E Shiloni; J T Vetto Journal: N Engl J Med Date: 1985-12-05 Impact factor: 91.245
Authors: A Ravaud; S Négrier; L Cany; Y Merrouche; M Le Guillou; J Y Blay; M Clavel; R Gaston; R Oskam; T Philip Journal: Br J Cancer Date: 1994-06 Impact factor: 7.640
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Authors: Carolina Muriel López; Emilio Esteban; Aurora Astudillo; Pablo Pardo; Jose Pablo Berros; Marta Izquierdo; Guillermo Crespo; Paula J Fonseca; Miguel Sanmamed; Pablo Martínez-Camblor Journal: Invest New Drugs Date: 2012-05-27 Impact factor: 3.850
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