Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer

James C. Yang, Richard M. Sherry, Seth M. Steinberg, Suzanne L. Topalian, Douglas J. Schwartzentruber, Patrick Hwu, Claudia A. Seipp, Linda Rogers-Freezer, Kathleen E. Morton, Donald E. White, David J. Liewehr, Maria J. Merino, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

664 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3127-3132
Number of pages6
JournalJournal of Clinical Oncology
Issue number16
StatePublished - Aug 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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