Oxaliplatin/fluorouracil-based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery: a systematic review and meta-analysis of randomized controlled trials

Abstract

Aim: Previous randomized controlled trials and meta-analyses have demonstrated the ineffectiveness of fluorouracil-based adjuvant chemotherapy for patients with rectal cancer who have undergone neoadjuvant chemoradiotherapy and subsequent surgery. The role of oxaliplatin/fluorouracil-based adjuvant chemotherapy in such patients is unknown. We performed a meta-analysis to evaluate the efficacy of oxaliplatin/fluorouracil-based adjuvant chemotherapy based on a comparison with fluorouracil-based adjuvant chemotherapy for patients with rectal cancer.

Method: A literature search of MEDLINE, Embase, Web of Science, Cochrane Library and ClinicalTrials.gov was performed to identify eligible studies. The primary end-point of interest was disease-free survival (DFS). The secondary end-points were overall survival, compliance and the incidence of Grade 3 or 4 toxicity.

Results: The literature search identified four randomized controlled trials that met the inclusion criteria for the meta-analysis, and 2793 patients with pathological TNM or clinical TNM Stage II or III disease were included. The meta-analysis showed that oxaliplatin/fluorouracil-based adjuvant chemotherapy was associated with a significantly improved DFS (hazard ratio 0.85; 95% CI 0.73-0.98; P = 0.03), comparable compliance (OR 1.18; 95% CI 0.95-1.46; P = 0.13) and a higher incidence of vomiting or nausea (OR 2.47; 95% CI 1.21-5.05; P = 0.01). No significant differences were observed between the groups with respect to overall survival and the incidence of leucopaenia, anaemia, thrombocytopaenia and diarrhoea.

Conclusion: Adjuvant oxaliplatin/fluorouracil-based chemotherapy can improve the DFS of patients after neoadjuvant chemoradiotherapy and radical surgery, compared with adjuvant fluorouracil-based chemotherapy. Data of the longer-term survival outcome are needed.

Keywords: Oxaliplatin; adjuvant chemotherapy; advanced rectal cancer; neoadjuvant chemoradiotherapy.