title: Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: a preliminary report.
abstract: OBJECTIVE
  We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer.
  
  
  METHODS
  Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m(2)/d and leucovorin 20 mg/m(2)/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles.
  
  
  RESULTS
  Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v. 70% at 4 years; P =.043). Twenty-three recurrences occurred in arm I and 38 in arm II (P =.047). Overall survival was not significantly different between arms I and II (84% v. 82% at 4 years; P =.387).
  
  
  CONCLUSIONS
  Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.
authors.affiliation: Department of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Hyeseung
authors.initials: H
authors.lastname: Bahng
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.forename: Jin-Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Chang-Sik
authors.initials: CS
authors.lastname: Yu
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Seung-Do
authors.initials: SD
authors.lastname: Ahn
authors.forename: Woo-Kun
authors.initials: WK
authors.lastname: Kim
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung-Shin
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil