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

PURPOSE:

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: David Sebag-Montefiore, Helen M Meadows, David Cunningham, Piers N Plowman, David C Hurman, Neville Davidson, Robert Grieve, Ed Levine, Rob Glynne-Jones
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 104 Issue 2 Pg. 155-60 (Aug 2012) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 22857859 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Mitomycin
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Anus Neoplasms (mortality, pathology, therapy)
• Carcinoma, Squamous Cell (mortality, pathology, therapy)
• Chemoradiotherapy (methods)
• Cisplatin (adverse effects, therapeutic use)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Follow-Up Studies
• Humans
• Maintenance Chemotherapy
• Male
• Maximum Tolerated Dose
• Middle Aged
• Mitomycin (adverse effects, therapeutic use)
• Neoplasm Invasiveness (pathology)
• Neoplasm Staging
• Pelvis (radiation effects)
• Pilot Projects
• Prospective Studies
• Radiotherapy, Adjuvant
• Survival Analysis
• Treatment Outcome
• United Kingdom