Docetaxel and cisplatin in patients with advanced or recurrent gastric cancer: a multicenter phase I/II study.
BACKGROUND
Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated the clinical efficacy and feasibility of this combination regimen.


METHODS
Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase I study, docetaxel was administered at a fixed dose of 60 mg/m(2) on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m(2). Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose level.


RESULTS
Recommended doses for the phase II evaluation were determined to be 60 mg/m(2) of docetaxel and 80 mg/m(2) of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients, respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0% (7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and the 1-year survival rate was 39.3%.


CONCLUSIONS
Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival.
Mitachi
Yashushi
Y
Department of Gastroenterology and Medical Oncology, Sendai Kosei Hospital, 4-15, Hirosecho, Aobaku, Sendai, Miyagi 980-0873, Japan.
Sakata
Yuh
Y
Ohtsu
Atsushi
A
Hyodo
Ichinosuke
I
Katsu
Kenichi
K
Sairenji
Motonori
M
Saitoh
Soh
S
Suwa
Toshikazu
T
Sato
Toshinobu
T
Miyata
Yoshinori
Y
D000328:Adult; D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D043823:Taxoids; D017855:Transferases (Other Substituted Phosphate Groups) / Q000187:drug effects; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D019883:Alkyl and Aryl Transferases; C112459:geranylpyrophosphate olivetolate geranyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C106504:UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase; D017239:Paclitaxel; D002945:Cisplatin