Randomized trial assessing the addition of interferon α-2a to fluorouracil and leucovorin in advanced colorectal cancer
Seymour MT., Slevin ML., Kerr DJ., Cunningham D., James RD., Ledermann JA., Perren TJ., McAdam WA., Harper PG., Neoptolemos JP., Nicholson M., Duffy AM., Stephens RJ., Stenning SP., Taylor I.
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.