Randomized trial assessing the addition of interferon α-2a to fluorouracil and leucovorin in advanced colorectal cancer

Purpose: To determine the effects of interferon α-2a (IFNα) on the efficacy and toxicity of fluorouracil (FUra) and leucovorin (LV) in patients with advanced colorectal cancer. Patients and Methods: Two hundred sixty chemotherapy-naive patients were randomized to FUra/LV alone or FUra/LV plus IFNα. All patients received: LV 200 mg/m2 intravenous (IV) infusion over 2 hours, then FUra 400 mg/m2 IV bolus plus 400 mg/m2 IV infusion over 22 hours, all repeated on day 2. Treatment was every 2 weeks for up to 12 cycles. Patients randomized to IFNα received 6 x 106 IU subcutaneously every 48 hours throughout. Objective response (OR) and toxicity were assessed conventionally; in addition, palliative benefit and adverse effects were assessed using quality-of-life (QoL) questionnaires. Results: There were no differences in OR rate, progression-free survival, or overall survival. OR rates in assessable patients were as follows: FUra/LV alone (n = 104), complete or partial response (OR) = 27%, no change (NC) = 36%; FUra/LV/IFNα (n = 101), OR = 28%, NC = 30%. Median survival was 10 months in both arms. Dose-limiting FUra toxicities were not significantly increased by co-administration of IFNα, and the delivered FUra dose-intensity was not significantly reduced. However, QoL was adversely affected: patients on IFNα were less likely to report improvement in pretreatment physical and psychologic symptoms, and more likely to report new or worsening symptoms. Conclusion: IFNα, at a dose that impaired QoL, did not improve the efficacy of FUra/LV. The power of this trial is sufficient to exclude with 95% confidence a benefit of 15% in OR or 10 weeks in median survival. Accordingly, we cannot recommend the use of IFNα as a clinical modulator of FUra/LV in the treatment of advanced colorectal cancer.