Low-Compared with High-Dose Regimen of Induction Chemotherapy in Locally Advanced Nasopharyngeal Cancer: A Systematic Review and Meta-analysis.

Introduction: International recommendation supports induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) as a new standard of care for locally advanced nasopharyngeal cancer (LA-NPC) which give a survival benefit. TPF is one of the IC regimens which consists of docetaxel (75 mg/m 2 , 1 hour infusion), cisplatin (75 mg/m 2 , 0.5-3 hours), and 5-fluorouracil (600 mg/m 2 , 4 days). Previous retrospective study in Chinese population reported low-dose TPF (L-TPF), consists of docetaxel (60 mg/m 2 ), cisplatin (65 mg/m 2 ), and then 5-fluorouracil (550 mg/m 2 /d; 5 days), showed better tolerance and compliance rates, with similar efficacy to high-dose TPF (H-TPF). Thus, we aim to evaluate the current evidence of the effect of L-TPF compared with H-TPF on survival and tolerance as IC in LA-NPC. Methods: Data were collected from PubMed, PubMed Central, and Science Direct, using combinations of keywords related to neoadjuvant chemotherapy (NAC) or IC, TPF dose regimen, and LA-NPC. The included studies investigated the efficacy and toxicity of IC with a TPF regimen. The quality of each included study was assessed using the Newcastle-Ottawa scale for cohort studies and the JADAD scale for randomized controlled trial (RCT). Only moderate- and good-quality studies were further evaluated in the meta-analysis. Results: A total of six studies consisting of 509 NAC patients were included. All the studies evaluated overall survival (OS) and progression-free survival (PFS). Quantitative analysis showed that L-TPF + CCRT significantly showed good OS (hazard ratio [HR] = 0.50; 95% confidence interval [CI], 0.33-0.76; p  = 0.001) but not PFS (HR = 0.45; 95% CI, 0.16-1.25; p  = 0.13). Common chemotoxicities that were found in both groups were neutropenia and anemia. Conclusion: L-TPF IC had a significant positive effect on the survival of LA-NPC patients. Further, larger multicenter RCT studies are needed to focus on evaluating the optimal TPF regimen dose in LA-NPC.