A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.
This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m(-2) b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m(-2) seven patients) were enrolled in this trial. At a dose of 70 mg m(-2) S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m(-2) demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m(-2) day(-1). A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway.
Ikeda
M
M
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. masikeda@ncc.go.jp
Okusaka
T
T
Ito
Y
Y
Ueno
H
H
Morizane
C
C
Furuse
J
J
Ishii
H
H
Kawashima
M
M
Kagami
Y
Y
Ikeda
H
H
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D016019:Survival Analysis; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid