Replacing 5-fluorouracil by capecitabine in localised squamous cell carcinoma of the anal canal: systematic review and meta-analysis

Abstract

BackgroundThe standard treatment for localised squamous cell carcinoma of the anal canal (SCCAC) is chemoradiotherapy (CRT) with infusional 5-fluorouracil (5-FU) and mitomycin. Because 5-FU and capecitabine have offered similar efficacy in many phase-III trials of solid tumours, studies have tested capecitabine in this setting of SCCAC. However, these studies are small and have reported variable results. Therefore, a systematic review and meta-analysis was performed.MethodsMedline, Scopus and Embase were searched for studies that evaluated the efficacy outcomes of capecitabine used as a substitute of 5-FU in the CRT of localised SCCAC. The primary endpoint was complete response rate (CRR) at 6 months. Metaprop analysis of reported CRR-based on pooled estimates of proportions with corresponding 95% confidence intervals (95%CI) were calculated on the base of the Freeman-Tukey double arcsine transformation.ResultsWe retrieved 300 studies, of which six met our eligibility criteria. The capecitabine dose ranged from 500 mg/m2 to 825 mg/m2 BID for 5 days per week during radiation. With a total of 218 patients, the median follow-up was 21.5 months (14–23). The pooled analysis of three trials (N = 132 patients) reported a CRR at 6 months of 88% (83%–94%), considering all clinical stages. The pooled analysis of overall CRR (N = 218 patients), evaluated at different intervals, showed an overall CRR of 91% (87%–95%). Rates of locoregional relapse varied from 3.2% to 21%. The majority of patients completed the planned radiotherapy dose (93.5%–100%) and any chemotherapy interruption was reported in up to 55.8% of patients.ConclusionsCapecitabine is an acceptable and more convenient alternative to infusional 5-FU in the CRT for localised SCCAC, offering similar clinical CRR to those reported by phase-III trials.

Treatment outcomes of patients with localized anal squamous cell carcinoma according to HIV infection: systematic review and meta-analysis

“…The standard treatment for localized anal cancer is based on infusional 5-fluorouracil (5-FU) or capecitabine (7), mitomycin (MMC) or cisplatin, concomitant with external radiation. This provides excellent results with overall local control rates greater than 80% (2,8).…”

Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort

“…NCCN, ESMO-ESSO-ESTRO, French Intergroup and relevant UK intensity-modulated radiation therapy (IMRT) guidelines support Capecitabine as an alternative option to 5-FU in radical CRT (18)(19)(20)(21). There is however a paucity of evidence for the tolerability and toxicity of Capecitabine when used in a doublet with MMC within this context (22,23). Notably, there is no relevant phase III data and the largest of the small number of relevant existing reports are retrospective, with significant heterogeneity in treatment parameters both within and across studies (24)(25)(26)(27)(28).…”

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center

“…The evidence of efficacy and manageable toxicity of the doublet MMC-C derived from retrospective studies (similar activity, but better tolerability of MMC-C versus MMC-5FU concomitant to IMRT, with lower hematologic toxicity and fewer treatment interruptions) and from phase II trials, with CR and locoregional control ranged from 77% to 89.1% and 79% to 94%, respectively, and high treatment completion rates despite the appearance of radiation dermatitis as the main toxicity (ranged from 23% to 63%). 32 – 40 The data regarding the combination of C with CDDP or oxaliplatin are more limited. 41 – 43 The main studies including C are reported in Table 5 .…”