Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2003 Aug 15;21(16):3127-32.
doi: 10.1200/JCO.2003.02.122.

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

James C Yang  1 , 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
Affiliations
Clinical Trial

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

James C Yang et al. J Clin Oncol. .

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.

PubMed Disclaimer

Figures

Fig 1
Fig 1
(A) Overall survival of patients randomly assigned to either low-dose (LD) or high-dose (HD) intravenous (IV) bolus interleukin-2 (IL-2). (B) Overall survival of patients concurrently randomized to received IL-2 by either LD IV bolus, HD IV bolus, or daily subcutaneous (SQ) administration.
Fig 2
Fig 2
Survival of patients completely responding to high-dose versus low-dose intravenous interleukin-2.
See this image and copyright information in PMC

References

    1. Rosenberg SA, Lotze MT, Muul L, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485–1492. - PubMed
    1. Lotze MT, Chang AE, Seipp CA, et al. High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer: Responses, treatment-related morbidity and histologic findings. JAMA. 1986;256:3117–3124. - PubMed
    1. Rosenberg SA, Yang JC, White DE, et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2. Ann Surg. 1998;228:319. - PMC - PubMed
    1. Fisher RI, Rosenberg SA, Sznol M, et al. High-dose aldesleukin in renal cell carcinoma: Long-term survival update. Cancer J Sci Am. 1997;3(suppl 1):S70–S72. - PubMed
    1. Parkinson DR, Abrams JS, Wiernik PH, et al. Interleukin-2 therapy in patients with metastatic malignant melanoma: A phase II study. J Clin Oncol. 1990;8:1650–1656. - PubMed

Publication types