Phase I pharmacokinetic study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer.
OBJECTIVE
A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.


METHODS
Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m(2), and intraperitoneally with an initial dose of 20 mg/m(2), stepped up to 30 or 40 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed.


RESULTS
The MTD was determined to be 30 mg/m(2), as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m(2). The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively.


CONCLUSIONS
Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials.
Ishigami
Hironori
H
Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. ishigami-tky@umin.net
Kitayama
Joji
J
Otani
Kensuke
K
Kamei
Takao
T
Soma
Daisuke
D
Miyato
Hideyo
H
Yamashita
Hiroharu
H
Hidemura
Akio
A
Kaisaki
Shoichi
S
Nagawa
Hirokazu
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage; D014018:Tissue Distribution; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel