title: Preoperative chemoradiation with irinotecan and capecitabine in patients with locally advanced resectable rectal cancer: long-term results of a Phase II study.
abstract: OBJECTIVE
  Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen.
  
  
  METHODS
  Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m(2) of irinotecan per week for 5 consecutive weeks and 1,650 mg/m(2) of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints.
  
  
  RESULTS
  In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death.
  
  
  CONCLUSIONS
  Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.
authors.affiliation: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Hyo Seong
authors.initials: HS
authors.lastname: Choi
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Jeong
authors.forename: Dae Kyung
authors.initials: DK
authors.lastname: Sohn
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin