title: A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer.
abstract: OBJECTIVE
  S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80 mg/m(2)/day given on days 1-21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).
  
  
  METHODS
  Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4 weeks of chemoradiotherapy. S-1 was given orally at a dose of 80 mg/m(2)/day twice daily on days 1-21. Radiotherapy was delivered in fractions of 1.25 Gy twice daily, 5 days per week for 4 weeks (total dose: 50 Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.
  
  
  RESULTS
  Fifty patients were enrolled in this phase II study. Median follow-up was 14.6 months (range 5.4-58.9 months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18-45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7 months (95% CI, 4.7-11.2 months) and 14.3 months (95% CI, 10.8-20.8 months), respectively. Survival rates at 1 and 2 years were 62 and 27%, respectively.
  
  
  CONCLUSIONS
  Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.
authors.affiliation: School of Health Sciences, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima, 890-8506, Japan. shinchi@m.kufm.kagoshima-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinchi
authors.forename: Kosei
authors.initials: K
authors.lastname: Maemura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mataki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurahara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sakoda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakajo
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D020266:Radiotherapy, Conformal / Q000379:methods*; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D005641:Tegafur / Q000008:administration & dosage*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid