Meta-analysis of adjunctive non-NK1 receptor antagonist medications for the control of acute and delayed chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing chemotherapy-induced symptom that may adversely impact the quality of life of cancer patients. We conducted a systematic search of the Pubmed, Bireme, and Cochrane databases for randomized clinical trials that were published in English and that evaluated the combination of adjunctive non-neurokinin 1 (NK1) antagonist drugs (i.e., neuroleptics, anticonvulsants, benzodiazepines, and cannabinoids) with 5-hydroxytryptamine 3 (5-HT3) antagonists for adult cancer patients who were scheduled to receive moderate or highly emetogenic chemotherapy. We employed the Review Manager (RevMan) Computer program Version 5.2 for statistical calculations. We included 13 studies with a total of 1,669 patients. We observed a higher complete protection for acute CINV with adjunctive medications (risk ratio (RR) = 0.55; 95 % confidence interval (CI) 0.30-1.01; p = 0.05; I (2) = 47 %), which was not the case for the delayed period (RR = 0.89; 95 % CI 0.73-1.10, p = 0.29, I (2) = 15 %). We also observed that these adjunctive medications significantly increased the complete control of nausea (RR = 0.72; 95 % CI 0.55-0.95; p = 0.02, I (2) = 83 %) and vomiting (RR = 0.61; 95 % CI 0.50-0.75; p < 0.00001; I (2) = 60 %). There was no subgroup analysis evidence of the superiority of any single group of adjunctive medications. We conclude that adjunctive non-NK1 antagonist medications may be useful for CINV control. Prospective randomized studies incorporating these low-cost medications into new regimens combining 5-HT3 and NK1 antagonists may be warranted.