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 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 journalArticle

Abstract

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
Volume21
Issue number16
DOIs
StatePublished - Aug 15 2003
Externally publishedYes

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Kidney Neoplasms
Interleukin-2
Renal Cell Carcinoma
Survival
Interleukin-13
Immunologic Factors
Interleukin-10
Hypotension
Survival Rate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yang, J. C., Sherry, R. M., Steinberg, S. M., Topalian, S., Schwartzentruber, D. J., Hwu, P., ... Rosenberg, S. A. (2003). Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. Journal of Clinical Oncology, 21(16), 3127-3132. https://doi.org/10.1200/JCO.2003.02.122

Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. / Yang, James C.; Sherry, Richard M.; Steinberg, Seth M.; Topalian, Suzanne; Schwartzentruber, Douglas J.; Hwu, Patrick; Seipp, Claudia A.; Rogers-Freezer, Linda; Morton, Kathleen E.; White, Donald E.; Liewehr, David J.; Merino, Maria J.; Rosenberg, Steven A.

In: Journal of Clinical Oncology, Vol. 21, No. 16, 15.08.2003, p. 3127-3132.

Research output: Contribution to journalArticle

Yang, JC, Sherry, RM, Steinberg, SM, Topalian, S, Schwartzentruber, DJ, Hwu, P, Seipp, CA, Rogers-Freezer, L, Morton, KE, White, DE, Liewehr, DJ, Merino, MJ & Rosenberg, SA 2003, 'Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer', Journal of Clinical Oncology, vol. 21, no. 16, pp. 3127-3132. https://doi.org/10.1200/JCO.2003.02.122
Yang, James C. ; Sherry, Richard M. ; Steinberg, Seth M. ; Topalian, Suzanne ; Schwartzentruber, Douglas J. ; Hwu, Patrick ; Seipp, Claudia A. ; Rogers-Freezer, Linda ; Morton, Kathleen E. ; White, Donald E. ; Liewehr, David J. ; Merino, Maria J. ; Rosenberg, Steven A. / Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 16. pp. 3127-3132.
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abstract = "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.",
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AU - Sherry, Richard M.

AU - Steinberg, Seth M.

AU - Topalian, Suzanne

AU - Schwartzentruber, Douglas J.

AU - Hwu, Patrick

AU - Seipp, Claudia A.

AU - Rogers-Freezer, Linda

AU - Morton, Kathleen E.

AU - White, Donald E.

AU - Liewehr, David J.

AU - Merino, Maria J.

AU - Rosenberg, Steven A.

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N2 - 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.

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