Induction chemotherapy decreases the rate of distant metastasis in patients with head and neck squamous cell carcinoma but does not improve survival or locoregional control: A meta-analysis

Abstract

The definitive effect of induction chemotherapy (IC) on locally advanced head and neck squamous cell carcinoma (HNSCC) remains uncertain and although randomized controlled trials are supposed to provide high levels evidence for clinical guidelines, the data thus far has been conflicted. In an effort to elucidate the potential benefit of IC, a meta-analysis of randomized controlled trials (1965-2011) was performed investigating the impact of IC on survival, locoregional control, distant metastasis, and toxicity in HNSCC. Kaplan-Meier curves were read by a digitizing software-Engauge Digitizer. Data combination was performed using the software-RevMan and trial level log hazard ratio (HR) and variance were pooled and presented. Among the 40 eligible trials, 28 trials encompassing 4189 patients receiving locoregional treatment with or without IC were included in the analysis. The cumulative benefit of IC on overall survival and distant metastasis was 6% (HR = 0.94, 95%CI = 0.87-1.01, P = 0.11) and 7% (95%CI = 0-13%, P = 0.05) respectively while for locoregional control a benefit was not observed as seen by the -2% (95%CI = -11% to 8%, P = 0.73) improved control rate. In a subsite analysis specifically for laryngeal preservation, IC did not significantly improve survival (P = 0.47). There was a significant benefit from the cisplatin and 5-fluorouracil (PF) protocols with an increase in overall survival of 13% (HR = 0.87, 95%CI = 0.78-0.97, P = 0.01), and a reduction in the 5-year distant metastasis rate of 11% (95%CI = 0-21%, P = 0.04). The occurrence of grade 3/4 mucositis, leukopenia and emesis was significantly lower in patients receiving IC compared to patients receiving concomitant chemoradiotherapy. In conclusion, there is not a significant benefit of the pooled IC regimens in HNSCC on survival or locoregional control. In contrast, IC does show significant benefit in the reduction of distant metastasis. When protocols using a PF regimen are analyzed independently, a significant improvement in survival and rate of distant metastases is observed while there is not a benefit in locoregional control. The routine use of IC is still debatable. IC could be applied on larynx preservation strategy.