Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) prior to surgery is a standard therapy for locally advanced rectal cancer, but the optimum regime is not conclusive. This meta-analysis evaluated various CRT regimens with regard to the rate of pathologic complete response (pCR) and toxic effects of grade ≥3. METHODS: The databases PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs) that compared neoadjuvant CRT regimes for treating patients with locally advanced rectal cancer, published before 28 December 2017. The primary end points were pCR and toxic effects. A network meta-analysis was applied. RESULTS: Fourteen RCTs (with 5,599 participants) involving the following eight regimens were included: fluorouracil (5FU) alone, or 5FU with oxaliplatin (OXA), cisplatin, or irinotecan (CPT-11); capecitabine (CAP) alone, or CAP with OXA or CPT-11; and CPT-11 with combined tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. The rate of pCR associated with CAP + OXA was significantly higher compared with 5FU alone; there were no significant differences among the other regimens. The toxicity of 5FU + OXA or CAP + OXA was significantly worse than that of 5FU alone or CAP alone. CAP + OXA and CAP were ranked, respectively, the most and second most effective regimens in terms of pCR rate. 5FU alone and CAP alone likely had the lowest and second lowest toxicity, respectively. CONCLUSION: Among the currently available CRT regimens for locally advanced rectal cancer, this meta-analysis indicated that CAP + OXA provides the superior clinical results. Adding OXA to 5FU or CAP significantly increases toxicity.