Multicenter feasibility study of combination therapy with fluorouracil, leucovorin and paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake.
OBJECTIVE
Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy in such patients.


METHODS
In the first phase of the study, we investigated the maximum tolerated dose and recommended dose in Cycle 1 of fluorouracil, l-leucovorin and paclitaxel, at two dose levels [Level 1 (n = 6): 5-fluorouracil/l-leucovorin/paclitaxel = 500/250/60 mg/m(2); Level 2 (n = 6): 600/250/80 mg/m(2) on Days 1, 8 and 15, every 28 days]. Nineteen additional patients at the recommended dose level were enrolled in the second phase to investigate the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy. The primary endpoint in the second phase was the completion rate of two cycles.


RESULTS
Dose-limiting toxicities were observed in a patient at Level 1 with Grade 4 gastrointestinal perforation (the site of primary tumor), and in two patients at Level 2 with Grade 3 febrile neutropenia and Grade 3 infection, respectively. In Cycle 2, treatment-related death occurred at Level 2 in one patient who had Grade 4 febrile neutropenia with pneumonia. The maximum tolerated dose was set at Level 2, and the recommended dose was determined as Level 1. In the second phase, the completion rate of two cycles was 92% and the ascites response was 44%. Median progression-free survival was 4.2 months and overall survival was 8.0 months. Grade 3/4 neutropenia was observed in 12% of patients.


CONCLUSIONS
Fluorouracil, l-leucovorin and paclitaxel at Level 1 is feasible as first-line treatment for peritoneal disseminated gastric cancer patients with massive ascites or inadequate oral intake.
National Cancer Center Hospital, Tokyo, Japan.
Satoru
S
Iwasa
Masahiro
M
Goto
Hirofumi
H
Yasui
Tomohiro
T
Nishina
Daisuke
D
Takahari
Norisuke
N
Nakayama
Koichi
K
Taira
Hitoshi
H
Kusaba
Nozomu
N
Fuse
Shuichi
S
Hironaka
Yasuhiro
Y
Shimada
Takako Eguchi
TE
Nakajima
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001201:Ascites / Q000209:etiology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004435:Eating; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007416:Intestinal Perforation / Q000209:etiology; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*
D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil