DOXIFLURIDINE AND LEUCOVORIN - AN ORAL TREATMENT COMBINATION IN ADVANCED COLORECTAL-CANCER

Purpose: This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether t he pharmacokinetics of dFUR and fluorouracil (FU) are affected by demo graphic and/or biologic parameters. Materials and Methods: One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dF UR 1,200 mg/m(2) on days 1 to 5, with the cycle being repeated every 1 0 days, Results: Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median r esponse duration was 4 months (range, 2 to 13) and the median survival time, 14 months, Among 46 pretreated patients, there were three CRs a nd three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12)and the median survival time, 12 months. No toxic deat hs were observed, The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients). Conclusion: This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also d etected in the patients previously treated with FU, which suggests inc omplete cross-resistance between the two drugs. The pharmacokinetic re sults suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those me asured after classical FU therapy. Under the experimental conditions u sed in this study, the interpatient variability of pharmacokinetic par ameters remains largely unexplained by the tested variables. (C) 1995 by American Society of Clinical Oncology.