OBJECTIVE: We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of interleukin-2 (IL-2) for the treatment of patients with unresectable or metastatic renal cell carcinoma (RCC). METHODS: We searched the literature to identify RCTs or meta-analyses of RCTs comparing treatment regimens with IL-2 to those without. Outcomes of interest included overall or progression-free survival, response rate, toxicity and quality of life. RESULTS: We identified 36 RCTs, and 6 met the eligibility criteria (1098 patients). We studied IL-2 alone and in combination with other agents, including interferon-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamoxifen. No trials comparing high-dose IL-2 to non-IL-2 regimens were identified. A meta-analysis of 1-year mortality data from the 6 trials did not show a difference between IL-2-based regimens and non-IL-2 controls. Two of the 6 trials detected statistically significant longer survival with IL-2 combined with IFN-a and 5-FU. Of the 4 trials that assessed progression-free survival, 3 reported significantly longer progression-free intervals with IL-2-based regimens. Five trials reported response rates; pooling the rates from these trials gave an overall weighted response rate of 13.3% (range 9%-39%) and 5.3% (range 0%-20%) for IL-2-containing regimens and non-IL-2 regimens, respectively. IL-2-based regimens were more toxic than were non-IL-2 controls; the most frequently reported grade 3-4 toxicities were hypotension (range 6%-68%), fever (2%-56%), nausea or vomiting or both (6%-34%), diarrhea (1%-28%) and cardiac toxicity (11%-25%). None of the trials reported health-related quality-of-life data. CONCLUSION: Non-high-dose IL-2 containing regimens do not provide superior treatment efficacy over non-IL-2-based regimens, with added toxicity, and therefore should not be used as standard treatment for patients with unresectable or metastatic RCC. High-dose IL-2 should only be used by experienced physicians in the context of a clinical trial or investigative setting.
OBJECTIVE: We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of interleukin-2 (IL-2) for the treatment of patients with unresectable or metastatic renal cell carcinoma (RCC). METHODS: We searched the literature to identify RCTs or meta-analyses of RCTs comparing treatment regimens with IL-2 to those without. Outcomes of interest included overall or progression-free survival, response rate, toxicity and quality of life. RESULTS: We identified 36 RCTs, and 6 met the eligibility criteria (1098 patients). We studied IL-2 alone and in combination with other agents, including interferon-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamoxifen. No trials comparing high-dose IL-2 to non-IL-2 regimens were identified. A meta-analysis of 1-year mortality data from the 6 trials did not show a difference between IL-2-based regimens and non-IL-2 controls. Two of the 6 trials detected statistically significant longer survival with IL-2 combined with IFN-a and 5-FU. Of the 4 trials that assessed progression-free survival, 3 reported significantly longer progression-free intervals with IL-2-based regimens. Five trials reported response rates; pooling the rates from these trials gave an overall weighted response rate of 13.3% (range 9%-39%) and 5.3% (range 0%-20%) for IL-2-containing regimens and non-IL-2 regimens, respectively. IL-2-based regimens were more toxic than were non-IL-2 controls; the most frequently reported grade 3-4 toxicities were hypotension (range 6%-68%), fever (2%-56%), nausea or vomiting or both (6%-34%), diarrhea (1%-28%) and cardiac toxicity (11%-25%). None of the trials reported health-related quality-of-life data. CONCLUSION: Non-high-dose IL-2 containing regimens do not provide superior treatment efficacy over non-IL-2-based regimens, with added toxicity, and therefore should not be used as standard treatment for patients with unresectable or metastatic RCC. High-dose IL-2 should only be used by experienced physicians in the context of a clinical trial or investigative setting.
Authors: S Negrier; B Escudier; C Lasset; J Y Douillard; J Savary; C Chevreau; A Ravaud; A Mercatello; J Peny; M Mousseau; T Philip; T Tursz Journal: N Engl J Med Date: 1998-04-30 Impact factor: 91.245
Authors: Robert J Motzer; Thomas E Hutson; Piotr Tomczak; M Dror Michaelson; Ronald M Bukowski; Olivier Rixe; Stéphane Oudard; Sylvie Negrier; Cezary Szczylik; Sindy T Kim; Isan Chen; Paul W Bycott; Charles M Baum; Robert A Figlin Journal: N Engl J Med Date: 2007-01-11 Impact factor: 91.245
Authors: J Atzpodien; H Kirchner; H J Illiger; B Metzner; D Ukena; H Schott; P J Funke; M Gramatzki; S Jürgenson; T Wandert; T Patzelt; M Reitz Journal: Br J Cancer Date: 2001-10-19 Impact factor: 7.640
Authors: Daila S Gridley; James M Slater; Xian Luo-Owen; Asma Rizvi; Stephen K Chapes; Louis S Stodieck; Virginia L Ferguson; Michael J Pecaut Journal: J Appl Physiol (1985) Date: 2008-11-06