title: EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer.
abstract: OBJECTIVE
  5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients.
  
  
  METHODS
  Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m2) on Day 1 and capecitabine on each RT treatment day in two divided doses (825 mg/m2 b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity.
  
  
  RESULTS
  Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred.
  
  
  CONCLUSIONS
  Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.
authors.affiliation: Mount Vernon Cancer Centre, Mount Vernon Hospital, Middlesex, United Kingdom. rob.glynnejones@nhs.net
authors.forename: Rob
authors.initials: R
authors.lastname: Glynne-Jones
authors.forename: Helen
authors.initials: H
authors.lastname: Meadows
authors.forename: Susan
authors.initials: S
authors.lastname: Wan
authors.forename: Simon
authors.initials: S
authors.lastname: Gollins
authors.forename: Martin
authors.initials: M
authors.lastname: Leslie
authors.forename: Ed
authors.initials: E
authors.lastname: Levine
authors.forename: Alec C
authors.initials: AC
authors.lastname: McDonald
authors.forename: Sun
authors.initials: S
authors.lastname: Myint
authors.forename: Les
authors.initials: L
authors.lastname: Samuel
authors.forename: David
authors.initials: D
authors.lastname: Sebag-Montefiore
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D000069287:Capecitabine; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000209:etiology; D011879:Radiotherapy Dosage; D012074:Remission Induction; D006113:United Kingdom
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil