Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer.
The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.
Yamaguchi
K
K
Department of Gastroenterology, Saitama Cancer Centre, Ina-machi, Kitaadachi-gun, Japan. k-yamaguchi@cancer-c.pref.saitama.jp
Shimamura
T
T
Hyodo
I
I
Koizumi
W
W
Doi
T
T
Narahara
H
H
Komatsu
Y
Y
Kato
T
T
Saitoh
S
S
Akiya
T
T
Munakata
M
M
Miyata
Y
Y
Maeda
Y
Y
Takiuchi
H
H
Nakano
S
S
Esaki
T
T
Kinjo
F
F
Sakata
Y
Y
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D010094:Oxonic Acid / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects; D005641:Tegafur / Q000009:adverse effects; D016896:Treatment Outcome
D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid