Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: A systematic review and practice guideline

Abstract

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 inter-est 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 interfer-on-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamox-ifen. 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 dif-ference 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 reg-imens. 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, respec-tively. 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 there-fore should not be used as standard treatment for patients with unresectable or metastatic RCC. High-dose IL-2 should only be used by experienced physi-cians in the context of a clinical trial or investigative setting. © 2007 Canadian Urological Association.