The Effectiveness and Safety of Metronomic Chemotherapy in Patients with Head and Neck Carcinoma: A Systematic Review and Meta-analysis

Abstract Background: Head and neck carcinoma, usually begins in the squamous cells, not only seriously endangers the quality of life, but brings a heavy financial burden for families and countries. Metronomic chemotherapy, a frequent administration of chemotherapeutic agents at a non-toxic dose, gives an alternative low-cost and tolerated approach for patients. We conducted a systematic review to find the effectiveness and safety of metronomic chemotherapy for head and neck cancer.Methods: We searched seven databases and Clinical.gov from the inception to July 14, 2021. The patients diagnosed head and neck cancer and older than 18 were included. Metronomic chemotherapy was defined as intervention. Randomized and non-randomized trials were all included. Quality assessment of included randomized control trials was performed using the Cochrane Risk-of-Bias criteria, cohort studies using The Newcastle-Ottawa Scale (NOS), single arm trials using the checklist recommended by The Agency for Healthcare Research and Quality (AHRQ). Studies were synthetized using a narrative approach. The indicators used for meta-analysis was hazard ratio (HR).Results: 310 Literatures were potentially eligible from 7 databases, finally 13 records were included. Five studies were of high quality, while eight were of moderate quality. The overall effect of HR for death of five trials reported had no statistically significant (HR=0.89, 95%CI 0.71-1.10). Subgroup analysis by different design showed a statistically significant HR (0.73, 95%CI 0.60-0.90) in randomized control trials while no significant difference in subgroup of prospective study design (HR=1.23, 95%CI 0.72-2.10). As for HR for PFS, there was no significant difference in overall effect of four studies. HR for PFS was 0.84 (95%CI 0.55-1.31). Subgroup analysis of study design showed that randomized control trials produced a significant HR (0.54, 95%CI 0.45-0.64), while prospective studies did not (1.25, 95%CI 0.73, 2.14).Conclusions: Metronomic chemotherapy has been an optimistic option for treatment for advanced head and neck cancer, especially in low income and medical resource-restricted regions.