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.


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.
Poorter
R L
RL
Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
Bakker
P J
PJ
Fockens
P
P
Taat
C W
CW
Bartelsman
J F
JF
Veenhof
C H
CH
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy*
D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil