Phase I/II trial of combination therapy with S-1 and weekly paclitaxel in patients with unresectable or recurrent gastric cancer.
OBJECTIVE
We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting.


METHODS
The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m(2)) was given orally on days 1-21 every 35-day cycle (rest on days 22-35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m(2), stepping up to 70 mg/m(2) in 10-mg/m(2) increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed.


RESULTS
The MTD of paclitaxel was estimated to be 60 mg/m(2), because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). In the phase II portion, 22 patients were evaluated with 50 mg/m(2) paclitaxel and 80 mg/m(2) S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2-75.6%). The median survival time was 283 days (95% CI, 218-508 days). The median number of treatment courses was 4 (range 1-10), indicating that this regimen could be given repeatedly.


CONCLUSIONS
This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.
Inada
Seisuke
S
Inada Clinic, 1-6-23-10 Kasuga, Kashiwazaki, Niigata 945-0074, Japan. inadaclinic@snow.plala.or.jp
Tomidokoro
Takashi
T
Fukunari
Hiroyuki
H
Sato
Tomomi
T
Hatano
Toru
T
Nishimura
Atsushi
A
Kawauchi
Yasuyuki
Y
Nikkuni
Keiya
K
Shimizu
Takeaki
T
Sato
Toshiteru
T
Yanagi
Masahiko
M
Takahashi
Satoru
S
Yoshida
Hideki
H
Sugita
Minoru
M
Hayashi
Tetsuji
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel