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


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).


CONCLUSIONS
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.
Yang
James C
JC
Surgery Branch, Biostatistics and Data Management Section, Department of Pathology, National Cancer Institute/NIH, Room 2B-37, Building 10, 9000 Rockville Pike, Bethesda, MD 20892, USA. james_yang@nih.gov
Sherry
Richard M
RM
Steinberg
Seth M
SM
Topalian
Suzanne L
SL
Schwartzentruber
Douglas J
DJ
Hwu
Patrick
P
Seipp
Claudia A
CA
Rogers-Freezer
Linda
L
Morton
Kathleen E
KE
White
Donald E
DE
Liewehr
David J
DJ
Merino
Maria J
MJ
Rosenberg
Steven A
SA
D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
D007376:Interleukin-2