title: Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option.
abstract: BACKGROUND
  Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC.
  
  
  METHODS
  One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m(-2)) on days 1-5 and 29-33, mitomycin C (MMC, 10 mg m(-2)) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m(-2) b.i.d. on weekdays), MMC (10 mg m(-2)) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity.
  
  
  RESULTS
  Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3-4) toxicity.
  
  
  CONCLUSIONS
  Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC.
authors.affiliation: 1] Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [2] Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [3] Division of Gastroenterology and Hepatology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Meulendijks
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Dewit
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: N B
authors.initials: NB
authors.lastname: Tomasoa
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: 1] Department of Pharmacy & Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands [2] Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: 1] Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [2] Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands [3] Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Cats
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil