Efficacy and safety of neoadjuvant chemotherapy in resectable oral squamous cell carcinomas: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to examine whether neoadjuvant chemotherapy (NAC) is useful against resectable oral squamous cell carcinomas. Three reviewers searched PubMed, Cochrane CENTRAL, and Ichushi-Web to identify clinical practice guidelines, systematic reviews (SRs), randomized controlled trials (RCTs), and prospective and retrospective non-randomized clinical (observational) studies according to pre-established eligibility and exclusion criteria. We systematically reviewed these selected articles and performed a meta-analysis of overall survival, disease-free survival, local recurrence, and distant metastasis. We used Review Manager 5.4 software for statistical analysis and rated the certainty of the evidence using the GRADE approach. Six RCTs (three studies) were eligible. The regimens involved were either PF (cisplatin+5-fluorouracil, 3 weekly, 3 cycles) or TPF (docetaxel+cisplatin+5-fluorouracil, 3 weekly, 2 cycles). The number of patients in the three studies were 198 (NAC-PF and Control group: 99 each), 256 (NAC-TPF and Control group: 128 each), and 68 (NAC-TPF and Control group: 34 each), respectively. The meta-analysis showed no difference between intervention and control groups in any of the outcomes of overall survival, disease-free survival, local recurrence, or distant metastases, and was considered at serious risk of bias, therefore the certainty of the evidence was 'very low' for all outcomes. NAC with multiple cytotoxic anticancer agents (PF/TPF) has very low efficacy and certainty of evidence for patients with resectable oral squamous cell carcinoma. Considering the risk of adverse events, we propose not performing NAC-PF/TPF.