A clinical trial with protracted infusion 5-fluorouracil and mitomycin C for localized squamous cell carcinoma of the anus

Asia Pac J Clin Oncol. 2019 Feb;15(1):75-81. doi: 10.1111/ajco.13106. Epub 2018 Dec 9.

Abstract

Purpose: Mitomycin C (MMC) plus standard 5-fluorouracil (FU) infusion in weeks 1 and 5 often contributes to radiotherapy interruptions and possibly less-than-ideal outcomes in anal cancer. This study was to evaluate alternative strategies for chemotherapy delivery that might be less toxic or more efficacious, and outcomes of patient-initiated treatment interruption for severe acute toxicity.

Materials and methods: This was a prospective, nonrandomized study for patients with T1-4N0-3M0 anal squamous carcinoma. Radiotherapy of 54 Gy in 30 fractions over 6 weeks was given with infusion FU 300 mg/m2 /day for 96 hours/week for 6 weeks plus bolus MMC at 10 mg/m2 on D1.

Results: Fifty patients were recruited (72% female). Median age was 60.5 years (35-84). Forty-seven patients (94%) received 54 Gy. Median duration of chemoradiation was 39 days (37-105). Grade 3 and 4 acute toxicity were observed in 66%. Thirty-one percent with severe acute toxicity developed severe late toxicity. Of those who experienced severe late skin toxicity, 29% did not have severe acute toxicity. Disease-free survival at 5 years was 74% (95% confidence interval [CI], 60-84), and at 9 years 61% (95% CI, 46-74). Overall survival at 5 years was 84% (95% CI, 71-92), and at 9 years 67% (95% CI, 50-81). Colostomy-free survival at 5 years was 70% (95% CI, 56-81), and at 9 years 57% (95% CI, 40-72).

Conclusion: It is feasible to deliver chemoradiation with bolus MMC and protracted infusion FU for anal cancer. Efficacy and toxicity of this regimen seem similar to conventional chemoradiation with FU/MMC. Acute skin toxicity is not a reliable predictor of severe late skin toxicity.

Keywords: acute toxicity; anal cancer; chemoradiation; late effects.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anal Canal
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Anus Neoplasms / drug therapy*
  • Anus Neoplasms / pathology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Mitomycin
  • Fluorouracil