Intermittent continuous infusion of 5-fluorouracil in combination with epirubicin and cisplatin in advanced gastric cancer: the importance of dose intensity.

BACKGROUND

Recently, high response rates have been reported in patients with advanced gastric cancer with a schedule of epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (5-FU). We modified this schedule based on the assumption that shorter treatment intervals are more convenient for patients and that cytokinetically based data showed that most gastric cancers have a relatively short potential doubling time of of less than 14 days.

PATIENTS AND METHODS

Fourteen patients with advanced gastric adenocarcinoma with progressive, measurable disease entered the study. Patients were treated from days 1 to 14 with 5-FU 200 mg/m2 per day as a continuous infusion using a portable infusion pump. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1. Courses were repeated every 4 weeks.

RESULTS

No responses were observed (response rate 0% [95% CI 0-23%]). Toxicity was mild. Grade 3 toxicity occurred in only 2 patients (14%). The median progression free survival was 3.5 months (range 2 to 17). The median survival was 6.5 months (range 2 to 31+).

CONCLUSIONS

The unexpected results of this study are most likely due to a diminished dose intensity. When comparing the results of several schedules with epirubicin, cisplatin, and 5-FU, it seems that the dose intensity for all three drugs may be important, but especially for 5-FU.