title: Phase I/II study of preoperative concurrent chemoradiotherapy with S-1 for locally advanced, resectable rectal adenocarcinoma.
abstract: OBJECTIVE
  To assess the maximum tolerability of a combination of S-1 and preoperative radiotherapy and to evaluate the feasibility and activity in patients with locally advanced rectal cancer.
  
  
  METHODS
  Patients (n = 30) with adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9) and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, and S-1 was orally administered twice a day on days 1-14 and 22-35. Surgical resection was scheduled 4-8 weeks after the completion of chemoradiation.
  
  
  RESULTS
  In phase I, the recommended dose (RD) of S-1 was 80 mg/m(2)/day, and the maximum-tolerated dose was never reached. A total of 27 cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase II, a pathological complete response (pCR) was observed in 6/27 patients (22%), pathological downstaging was observed in 21/27 patients (78%), and a tumor volume reduction of 69 ± 22% was obtained. These results were similar to the previously reported pCR rates of 16-18%, pathological downstaging rates of 49-59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine. Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very mild. Hand-foot syndrome was not observed.
  
  
  CONCLUSIONS
  The efficacy of chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for chemoradiotherapy with capecitabine, but the adverse events were much milder, although further study is warranted.
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Isehara, Japan. sadahiro@is.icc.u-tokai.ac.jp
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kazutake
authors.initials: K
authors.lastname: Okada
authors.forename: Akemi
authors.initials: A
authors.lastname: Kamijo
authors.forename: Chieko
authors.initials: C
authors.lastname: Murayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akiba
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid