title: Randomized clinical trial of adjuvant chemotherapy with S-1 versus gemcitabine after pancreatic cancer resection.
abstract: BACKGROUND
  Randomized studies of adjuvant chemotherapy using gemcitabine suggest a survival benefit after resection of pancreatic cancer. S-1 has also been shown to prolong survival in patients with unresectable pancreatic cancer. This study compared the effects of adjuvant chemotherapy with S-1 or gemcitabine after resection of pancreatic cancer in a randomized trial.
  
  
  METHODS
  Patients who had undergone resection of pancreatic cancer were registered in this randomized clinical trial. The primary endpoint was disease-free survival (DFS). Expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNAs in cancer tissues were measured as indicators of fluoropyrimidine sensitivity.
  
  
  RESULTS
  Of 57 patients registered, 29 were allocated to the S-1 group and 28 to gemcitabine. DFS tended to be better with S-1 (median 14·6 (90 per cent c.i. 8·8 to 28·4) months versus 10·5 (7·0 to 28·4) months in the gemcitabine group; P = 0·188), with a similar pattern for overall survival: 21·5 (95 per cent c.i. 14·4 to 42·3) and 18·0 (13·3 to 42·8) months respectively (P = 0·293). When patients were divided into subgroups based on high or low DPD and TS expression, those with a DPD level below the median of 0·88 or a TS level of at least 2·00 had a significant prolongation of DFS after S-1 treatment compared with gemcitabine (P = 0·008 and P = 0·035 respectively).
  
  
  CONCLUSIONS
  Overall, S-1 did not improve DFS compared with gemcitabine after pancreatic cancer resection, but there seemed to be a DFS advantage in patients with low expression of DPD or high expression of TS. Reference number: UMIN000009118 (http://www.umin.ac.jp/ctr/).
authors.affiliation: Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Katoh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; 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; D010094:Oxonic Acid / Q000008:administration & dosage*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011182:Postoperative Care / Q000379:methods*; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D005641:Tegafur / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine