Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial.
OBJECTIVE
This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC).


METHODS
Eligibility requirements were resected locally advanced (LA; T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history.


RESULTS
Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival.


CONCLUSIONS
One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.
Clark
Joseph I
JI
Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. jclark@lumc.edu
Atkins
Michael B
MB
Urba
Walter J
WJ
Creech
Steven
S
Figlin
Robert A
RA
Dutcher
Janice P
JP
Flaherty
Larry
L
Sosman
Jeffrey A
JA
Logan
Theodore F
TF
White
Richard
R
Weiss
Geoffrey R
GR
Redman
Bruce G
BG
Tretter
Christopher P G
CP
McDermott
David
D
Smith
John W
JW
Gordon
Michael S
MS
Margolin
Kim A
KA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D007376:Interleukin-2