Abstract | PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
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Authors | Sylvie Négrier, David Perol, Alain Ravaud, Jacques O Bay, Stéphane Oudard, Sylvie Chabaud, Pierre Fargeot, Remy Delva, Gael Deplanque, Gwenaelle Gravis, Bernard Escudier, French Immunotherapy Group |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 14
Issue 18
Pg. 5907-12
(Sep 15 2008)
ISSN: 1078-0432 [Print] United States |
PMID | 18794104
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interferon-alpha
- Interleukin-2
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Carcinoma, Renal Cell
(drug therapy)
- Disease-Free Survival
- Drug Administration Schedule
- Female
- Humans
- Injections, Intravenous
- Injections, Subcutaneous
- Interferon-alpha
(administration & dosage)
- Interleukin-2
(administration & dosage)
- Kidney Neoplasms
(drug therapy)
- Male
- Middle Aged
- Neoplasm Metastasis
- Prognosis
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