Feasibility study of S-1 and intraperitoneal docetaxel combination chemotherapy for gastric cancer with peritoneal dissemination.
BACKGROUND
Gastric cancer with cancer cells on peritoneal cytology has very poor prognosis because of the existence of simultaneous peritoneal metastasis. Here we performed a dose-escalation study of intraperitoneal docetaxel (DTX) combined with S-1 to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer with peritoneal dissemination.


METHODS
Twelve gastric cancer patients with positive cytology were enrolled in this study. Peritoneal lavage specimens were obtained under local anesthesia or staging laparoscopy before treatment and the combination chemotherapy was applied in patients with positive cytology. DTX was administered on day 1 intraperitoneally with initial dose of 40 mg/m(2), stepped up to 50 or 60 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day on days 1-14, followed by 7 days of rest. After two cycles of the combination chemotherapy, staging laparoscopy was performed to evaluate the effect of the chemotherapy. Simultaneous gastrectomy was performed in cases without peritoneal deposits at staging laparoscopy.


RESULTS
The MTD of intraperitoneal DTX was not determined and the RD was defined as 60 mg/m(2) because dose-limiting toxicity occurred in only one patient at level II (DTX: 50 mg/m(2)). Out of twelve patients given the combination chemotherapy, nine had cytologically negative peritoneal lavage and had no peritoneal metastases at surgery after chemotherapy.


CONCLUSIONS
The combined chemotherapy of S-1 plus intraperitoneal DTX was revealed to be safe and may be effective for gastric cancer with peritoneal dissemination.
Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. yfujiwara@gesurg.med.osaka-u.ac.jp
Yoshiyuki
Y
Fujiwara
Toshiro
T
Nishida
Shuji
S
Takiguchi
Kiyokazu
K
Nakajima
Hiroshi
H
Miyata
Makoto
M
Yamasaki
Kazuyoshi
K
Yamamoto
Jeong-Ho
JH
Moon
Masaki
M
Mori
Yuichiro
Y
Doki
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D012074:Remission Induction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid