Toxicity, Tolerability and Compliance of Concurrent Capecitabine or 5-Fluorouracil in the Radical Management of Anal Cancer with Single-Dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort
Menée au Royaume-Uni à partir de données portant sur 242 patients atteints d'un carcinome épidermoïde de l'anus, cette étude évalue la toxicité et la tolérabilité de l'association capécitabine-mytomicine par rapport à l'association 5-fluorouracile-mytomicine dans le cadre d'un traitement combinant chimiothérapie et radiothérapie avec modulation d'intensité
Purpose : Chemoradiotherapy (CRT) with mitomycin C (MMC) and 5-fluouracil (5-FU) is established as the standard of care for the radical management of patients with anal squamous cell carcinoma (ASCC). There is emerging use of the oral fluoropyrimidine-derivative capecitabine as an alternative to 5-FU despite limited evidence for its tolerability and toxicity. Methods & Materials : A national cohort evaluation of anal cancer management within the United Kingdom National Health Service was undertaken between February and July 2015. Toxicity rates were prospectively recorded. For this analysis we report ASCC patients managed with intensity modulated radiotherapy (IMRT) and a single dose of MMC with either 5-FU (5-FU/MMC) or capecitabine (capecitabine/MMC). All were treated with radical intent and in accordance with UK guidance. Results : Of the 242 patients received from 40 centres across the UK, 147 met inclusion criteria; 52 of whom were treated with capecitabine/MMC, and 95 with 5-FU/MMC. There were no treatment related deaths and there was no overall difference in the proportion of patients experiencing any grade 3 or above toxicity between the capecitabine and 5-FU groups (45% vs. 55%; p=0.35). However, significantly fewer patients in the capecitabine/MMC group experienced grade 3 haematological toxicity (4% vs. 27%; p=0.001). A lower proportion of patients completed their planned chemotherapy course in the capecitabine cohort, though this did not reach statistical significance (81% vs. 90%; p=0.21). Median radiotherapy treatment duration was 38 (IQR 38-39) days for both groups. There was no difference in 1-year oncological outcomes. Conclusion : Capecitabine/MMC resulted in similar levels of grade 3-4 toxicity overall as compared with 5-FU/MMC as CRT for ASCC, although there were differences in patterns of observed toxicities with less haematological toxicity with capecitabine. Further studies of capecitabine/MMC are required to understand the acute toxicity profile and long term oncological outcomes of this combination with IMRT in ASCC.