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

Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):119-26. doi: 10.1016/j.ijrobp.2007.12.012. Epub 2008 May 9.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Anus Neoplasms / drug therapy*
  • Anus Neoplasms / radiotherapy*
  • Capecitabine
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Diarrhea / etiology
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Mitomycin / adverse effects
  • Neoplasm Recurrence, Local
  • Neutropenia / etiology
  • Radiotherapy Dosage
  • Remission Induction
  • United Kingdom

Substances

  • Deoxycytidine
  • Mitomycin
  • Capecitabine
  • Fluorouracil