Randomized study of intravenous versus subcutaneous interleukin-2, and IFNalpha in patients with good prognosis metastatic renal cancer.
OBJECTIVE
Metastatic renal cancer patients with a single metastatic site are potentially amenable to interleukin 2 (IL-2) + IFN-alpha. A French immunotherapy intergroup multicenter trial assessed the potential benefit of i.v. over s.c. administration of IL-2 in this combination.


METHODS
Untreated patients with one metastatic site were randomized to continuous i.v. infusion (18 x 10(6) IU/m(2)/d; arm A) or twice daily s.c. injections (9 x 10(6) or 18 x 10(6) IU; arm B) of IL-2, associated with s.c. IFN-alpha (6 x 10(6) IU) 3 days per week in both arms. Tumor response was assessed (WHO criteria) at weeks 12 and 24 to 26. The primary end point was overall survival, with an expected 15% improvement at 4 years with i.v. IL-2. The planned sample size was 220 (80% power, 5% significance, one-sided test). Intent-to-treat analysis was done and survivals were compared using log-rank tests.


RESULTS
From January 2000 to January 2005, 80 and 75 patients were randomized to arms A and B, respectively. Enrollment was stopped early because of low accrual; analysis was done at 42.5 months median follow-up. Patient characteristics were well balanced between groups. Response rates were 17.9% versus 21.3% in arms A and B. Progression-free survival rates were not significantly different. Overall survival difference was not significant: median 33 months (95% confidence interval, 27.0-40.2; P = 0.202).


CONCLUSIONS
In combination with IFN-alpha in selected, good prognosis metastatic renal cell carcinoma patients, i.v. IL-2 offers no significant advantage over s.c. IL-2 and induces higher toxicity. Although i.v. IL-2 induced longer responses, it seems unreasonable to continue recommending this regimen after the recent introduction of more effective therapies.
Négrier
Sylvie
S
Université de Lyon, Centre Léon Bérard, Medical Oncology Department, Institut National de la Sante et de la Recherche Medicale U.590 and Biostatistics Unit, Centre Léon Bérard, Lyon Cedex 08, France. reynaud@lyon.fnclcc.fr
Perol
David
D
Ravaud
Alain
A
Bay
Jacques O
JO
Oudard
Stéphane
S
Chabaud
Sylvie
S
Fargeot
Pierre
P
Delva
Remy
R
Deplanque
Gael
G
Gravis
Gwenaelle
G
Escudier
Bernard
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis
D016898:Interferon-alpha; D007376:Interleukin-2