A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel (FLTAX) as first-line therapy for advanced gastric cancer.
OBJECTIVE
To determine the dose-limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil (5-FU) and weekly paclitaxel in patients with advanced gastric cancer (GC).


METHODS
Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled. Paclitaxel was administered as a 1-h intravenous (i.v.) infusion followed by 5-FU as a bolus i.v. infusion on Days 1, 8 and 15. A 2-h i.v. infusion of l-leucovorin was started at the same time as the paclitaxel infusion on Days 1, 8 and 15. Treatment cycles were repeated every 28 days until disease progression or unacceptable toxicity occurred. Patients were scheduled to receive 5-FU, l-leucovorin and paclitaxel at four dose levels (mg/m(2)/week): 500/250/60 (level 1), 500/250/80 (level 2), 600/250/80 (level 3) and 600/250/100 (level 4), respectively.


RESULTS
Eighteen patients were enrolled. During the first cycle of the highest dose level (level 4), two of the six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash. Furthermore, three of the four patients who received the second consecutive cycle of treatment at dose level 4 had Grade 4 neutropenia. Dose level 3 was thus determined to be the MTD. Eleven (61%) of the 18 patients had partial responses, and the median progression-free survival time was 6.8 months.


CONCLUSIONS
The MTD and the recommended dose for phase II studies of this regimen were determined to be 5-FU 600 mg/m(2)/week, l-leucovorin 250 mg/m(2)/week and paclitaxel 80 mg/m(2)/week.
Matsubara
Junichi
J
Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan. junjun0808@hotmail.com
Shimada
Yasuhiro
Y
Takashima
Atsuo
A
Takahari
Daisuke
D
Hirashima
Yoshinori
Y
Okita
Natsuko T
NT
Nakajima
Takako E
TE
Kato
Ken
K
Hamaguchi
Tetsuya
T
Yamada
Yasuhide
Y
Shirao
Kuniaki
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil