Improved tolerability and quality of life with maintained efficacy using twice-daily low-dose interferon-α-2b -: Results of a randomized phase II trial of low-dose versus intermediate-dose interferon-α-2b in patients with metastatic renal cell carcinoma

BACKGROUND. in vivo data have shown a more potent antiangiogenic effect and a higher antitumor activity of low-dose interferon (IFN) given twice daily. In a randomized Phase II trial, the authors tested the hypothesis that twice-daily low-dose IFN is more effective than daily intermediate-dose IFN in patients with metastatic renal cell cancer (MRCC). METHODS. A total of 118 patients (59 per arm) were randomly assigned to receive IFN at a dose of 0.5 million units (MU) given subcutaneously twice daily (IFN1) or IFN at a dose of 5 MU given subcutaneously daily (IFN5). The primary end-point was progression-free survival (PFS). Secondary endpoints included response rate (RR), overall survival (OS), toxicity, and quality of life (QOL). RESULTS. There were no significant differences in either PFS or OS between IFN1 and IFN5 (median of 3.7 months and median of 3.4 months PFS, respectively; median of 25.5 months and median of 17.5 months OS, respectively). The RRs were identical in the 2 arms (6.7%; 95% confidence interval [95% CI], 1.8-16.5%). Two patients, I in each arm, remained in complete remission at the time of last follow-up, at 45+ and 38+ months from treatment. Thirty-two patients receiving IFN5 and 19 patients receiving IFN1 experienced Grade 3 or higher adverse events (graded using the National Cancer Institute Common Toxicity Criteria [version 2.0]) (P=.025). Eighteen patients receiving IFN5 and 4 patients receiving IFN1 had dose reductions (P=.002). There was a significant deterioration in QOL and an increase in depression associated with IFN5 but no change was noted with IFN1. CONCLUSIONS. Compared with IFN5, IFN1 is neither more nor less effective but is less toxic, with a better reported QOL. These results may have implications for the design of combination regimens incorporating IFN with targeted agents.