title: A phase II trial of neoadjuvant capecitabine combined with hyperfractionated accelerated radiation therapy in locally advanced rectal cancer.
abstract: OBJECTIVE
  Preoperative treatment of rectal cancer with combined chemotherapy and radiation therapy has become a widely accepted strategy. The current challenge is to improve outcomes whereas minimizing morbidity and maximizing the potential for a sphincter sparing procedure. This study sought to evaluate the safety and efficacy of a combination of 2 novel approaches-accelerated, hyperfractionated radiation therapy and twice daily oral capecitabine.
  
  
  METHODS
  Consenting patients with locally advanced T3-T4, N0-1, M0 rectal adenocarcinoma, located no further than 15 cm from the anal verge, were treated with twice daily fractions of 1.2 Gy M-F to a total of 50.4 Gy for T3 lesions and 55.2 Gy for T4 lesions. Concomitantly, the patients received capecitabine 825 mg/m twice per day 7 days per week. Patients were operated on 4 to 6 weeks after completion of therapy.
  
  
  RESULTS
  Sixteen of 17 enrolled patients were eligible and all 16 completed the full course of treatment including definitive surgery. Eleven patients had a sphincter sparing procedure and 5 had an abdominoperineal resection. Tumor and/or nodal downstaging occurred in 81% of patients, 100% of resections were R0, and the sphincter preservation rate was 68%. There were 18% pathologic complete remissions and 68% of specimens were node negative with an additional 12% Nx owing to transanal excision. The therapy was well tolerated and there were no unexpected toxicities with only diarrhea reaching grade 3 in 4 patients.
  
  
  CONCLUSIONS
  This novel approach to preoperative treatment of rectal adenocarcinoma was well tolerated and effective. Comparison with more established approaches appears justified.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. marshrd@medicine.ufl.edu
authors.forename: Robert de W
authors.initials: Rde W
authors.lastname: Marsh
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: George
authors.forename: Tariq
authors.initials: T
authors.lastname: Siddiqui
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zlotecki
authors.forename: Stephen
authors.initials: S
authors.lastname: Grobmyer
authors.forename: Steven
authors.initials: S
authors.lastname: Hochwald
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Bradley
authors.initials: B
authors.lastname: Larson
authors.forename: Judy
authors.initials: J
authors.lastname: King
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000209:etiology; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil