ACTIVITY OF CONTINUOUS-INFUSION 5-FLUOROURACIL IN PATIENTS WITH ADVANCED COLORECTAL-CANCER CLINICALLY RESISTANT TO BOLUS 5-FLUOROURACIL

We have recently demonstrated that continuous-infusion (CI) 5-fluorora cil (FU) eradicates human colon carcinoma cells made resistant to bolu s FU in vitro. In addition, in the same experimental system, the mecha nisms of resistance to pulse and CI FU were found to be different. The se observations led us to test the clinical activity of a standard reg imen of CI FU (300 mg/m(2) per day) in a cohort of 15 patients with ad vanced measurable colorectal cancer who were in progression after havi ng failed to respond to bolus treatment with FU alone (3 patients) or FU combined with high-dose 6-S-leucovorin (LV) (12 patients). The medi an age of the patients was 68 years, and their median Eastern Cooperat ive Oncology Group performance status (ECOG PS) was 1. No myelotoxicit y was observed. Mild diarrhea, mucositis, and vomiting occurred in 32% , 26%, and 19% of the patients, respectively, with no WHO grade 3 or 4 episodes being noted. In all, 6 of 15 patients complained of hand-foo t syndrome, which was severe in 2 instances, lasting approximately 1 w eek. Overall, 1 partial response and 6 instances of disease stabilizat ion, including 3 minor responses, were obtained both in patients who h ad been pretreated with pulse FU alone and in patients who had failed first-line treatment with FU + LV. Finally, 8 patients failed CIFU. In conclusion, these results, obtained in patients who were clearly prog ressing after having failed first-line treatment, support our experime ntal finding that resistance to bolus FU may be overcome by CI FU and extend this possibility to patients who are resistant to bolus treatme nt with FU + LV.