A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer.
OBJECTIVE
The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer.


METHODS
Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4).


RESULTS
Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months.


CONCLUSIONS
Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m(2)/week and an S-1 dose of 80 mg/m(2)/day in further studies with this schedule.
Ueno
Hideki
H
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. hiueno@ncc.go.jp
Okusaka
Takuji
T
Ikeda
Masafumi
M
Ishiguro
Yoriko
Y
Morizane
Chigusa
C
Matsubara
Junichi
J
Furuse
Junji
J
Ishii
Hiroshi
H
Nagase
Michitaka
M
Nakachi
Kohei
K
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine