Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.
OBJECTIVE
The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.


METHODS
Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m(2)/day.


RESULTS
Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80 mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively.


CONCLUSIONS
The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.
Sudo
Kentaro
K
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana, Chiba, Japan.
Yamaguchi
Taketo
T
Ishihara
Takeshi
T
Nakamura
Kazuyoshi
K
Shirai
Yoshihiko
Y
Nakagawa
Akihiko
A
Kawakami
Hiroyuki
H
Uno
Takashi
T
Ito
Hisao
H
Saisho
Hiromitsu
H
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy / Q000379:methods; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid