Interferon-alfa in the treatment of patients with inoperable locally advanced or metastatic renal cell carcinoma: a systematic review

A systematic review was undertaken to determine whether interferon-alfa (IFN-alpha) is an effective treatment for patients with inoperable locally advanced or metastatic renal cell carcinoma (mRCC). MEDLINE, EMBASE, the Cochrane Library, guideline databases and relevant meeting proceedings were searched. Randomized clinical trials (RCTs) or meta-analyses comparing IFN-alpha-containing regimens to placebo or non-immunotherapy controls, and that reported response rate, survival, toxicity or quality of life data were eligible. Two systematic reviews and eight RCTs met the selection criteria. A Cochrane review updated in 2005 reported higher response rates and reduced one-year mortality based on 4 RCTs in patients who received IFN-alpha. Of the eight RCTs, three reporting objective response rate showed significant differences favouring IFN-alpha. Two of five trials reporting survival data showed longer median survival in the IFN-alpha group. Adverse effects of IFN-alpha were consistent across the trials with increased intensity and frequency concordant with increased IFN-alpha dose. Meta-analyses of seven RCTs for objective response and six RCTs for mortality favoured IFN-alpha: odds ratio 6.87 (95% Confidence Interval [CI], 3.29 to 14.35) and hazard ratio 0.79 (95% CI, 0.69 to 0.91), respectively. The effectiveness of IFN-alpha in mRCC has been subject to skepticism. As IFN-alpha has been used as a control arm in RCTs of new targeted therapies, therapies which not all patients may have access to, information about its effectiveness remains relevant. These data confirm genuine, if modest, effectiveness of IFN-alpha in mRCC.