Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer.
BACKGROUND
Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents.


METHODS
Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP.


RESULTS
In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18 mg/m2, with CDDP 3 mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16 mg/m2 with CDDP, 3 mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%).


CONCLUSIONS
The RD was determined to be TXL 14 mg/m2, with CDDP 3 mg/m2.
Department of Gastroenterology, Saitama Cancer Center Hospital, Komuro 818, Ina-machi, Saitama, 362-0806, Japan.
Kensei
K
Yamaguchi
Tomotaka
T
Shimamura
Yoshito
Y
Komatsu
Akinori
A
Takagane
Takashi
T
Yoshioka
Soh
S
Saitoh
Masaki
M
Munakata
Yu
Y
Sakata
Tsukasa
T
Sato
Tatsuhiro
T
Arai
Hiroshi
H
Saitoh
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D015996:Survival Rate
D017239:Paclitaxel; D002945:Cisplatin