Biochemical modulation of 5-fluorouracil by leucovorin with or without interferon-alpha-2c in patients with advanced colorectal cancer: Final resultsof a randomised phase III study

5-Fluorouracil (5-FU) remains the mainstay of treatment for advanced colore ctal carcinoma, although response rates are generally less than 20%. Improv ed therapeutic efficacy has been reported using biochemical modulation of 5 -FU by leucovorin (LV) or interferon alpha (IFN), the combination of 5-FU/L V frequently considered as standard therapy in metastatic colorectal cancer . In an attempt to enhance the cytotoxicity of 5-FU, a prospective randomis ed trial was initiated to compare 5-FU/LV with 5-FU/LV plus IFN. Patients w ere randomised to receive either LV, 100 mg/m(2) intravenously (i.v.), foll owed by 5-FU, 500 mg/m(2) as a 1-h i.v. infusion, daily for 4 days, followe d by weekly infusions until week 8, or the same regimen of 5-FU/LV plus IFN -alpha-2c, 30 mu g subcutaneously (s.c.), three times weekly. Cycles were r epeated after a 2-week rest period. Among 269 enrolled patients, 219 were a vailable for response and 243 for toxicity. An objective tumour response wa s observed in 38 of 107 (36%) and 28 of 112 (25%) patients in the treatment arms with and without IFN, respectively (difference not significant). Ther e was no significant difference between the two groups in response duration (median 8.4 versus 12.1 months), time to treatment failure (median 6.5 ver sus 4.9 months), or overall survival (median 10.0 versus 12.6 months). Howe ver, patients in the IFN arm experienced significantly more haematological and gastrointestinal toxicity and more frequent alopecia. In conclusion, th e addition of IFN to 5-FU/LV in the schedules and doses used in the study d id not provide any clinical benefit over 5-FU/LV alone and cannot be recomm ended for routine use in the treatment of advanced colorectal cancer. (C) 1 999 Elsevier Science Ltd. All rights reserved.