Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer.
In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy x 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m(-2) day(-1) on days 1-7 and 15-21 (level 1), 1-14 (level 2), and 1-21 (level 3a) and 80 mg m(-2) day(-1) on days 1-21 (level 3b) and 1-28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19-9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m(-2) day(-1) given on days 1-21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.
Shinchi
H
H
Department of Surgical Oncology and Digestive Surgery, Kagoshima University, Kagoshima, Japan. shinchi@m.kufm.kagoshima-u.ac.jp
Maemura
K
K
Noma
H
H
Mataki
Y
Y
Aikou
T
T
Takao
S
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D011878:Radiotherapy / Q000379:methods*; D016019:Survival Analysis; D005641:Tegafur / Q000633:toxicity*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid