title: Three cytotoxic drugs combined with pelvic radiation and as maintenance chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): long-term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and cisplatin.
abstract: OBJECTIVE
  Phase III trials in the 1990s for squamous cell carcinoma of the anus (SCCA) demonstrated 5-fluorouracil (5FU) and mitomycinC (MMC) chemoradiation (CRT) improved outcome compared to radiation (RT) alone, but local recurrence remained significant. This prospective pilot study intensified treatment by integrating 3 cytotoxic drugs into CRT and maintenance chemotherapy.
  
  
  METHODS
  CRT comprised 5-FU 1000 mg/m(2) days 1-4,29-32, MMC 10 mg/m(2) day 1 and Cisplatin (CDDP) 60 mg/m(2) days1 and 29, with 45 Gy in 25 daily fractions, followed by a 15 Gy boost. Maintenance chemotherapy started 4-8 weeks later, three courses repeated every 21 days, using 5-FU/CDDP doses above, with MMC reduced to 7 mg/m(2) and administered with the first and third cycles.
  
  
  RESULTS
  In CRT only 14/19 (74%) patients received protocol-defined chemotherapy doses in week 5. Compliance to maintenance chemotherapy was poor. 15/19 started cycle 1, 13 started cycle 2 and 11 cycle 3. 17/19 experienced G3-G5 toxicity (16 Grade 3/4 and one Grade 5). 16/19 patients (84%) remain alive and disease-free - median follow-up 79 months (34-115).
  
  
  CONCLUSIONS
  Despite favourable results, the significant toxicity and low compliance of the three-drug CRT regimen used, deemed it unsuitable for testing in a phase III trial. A two-drug maintenance regimen was explored in the ACT II trial.
authors.affiliation: University of Leeds, St. James's Institute of Oncology, Leeds, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sebag-Montefiore
authors.forename: Helen M
authors.initials: HM
authors.lastname: Meadows
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Piers N
authors.initials: PN
authors.lastname: Plowman
authors.forename: David C
authors.initials: DC
authors.lastname: Hurman
authors.forename: Neville
authors.initials: N
authors.lastname: Davidson
authors.forename: Robert
authors.initials: R
authors.lastname: Grieve
authors.forename: Ed
authors.initials: E
authors.lastname: Levine
authors.forename: Rob
authors.initials: R
authors.lastname: Glynne-Jones
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects / Q000627:therapeutic use; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010388:Pelvis / Q000528:radiation effects; D010865:Pilot Projects; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil