Chemotherapy induced nausea and vomitus (CINV) depends on pharmacogenetisc of the 5-HT-3-Receptor

Introduction: Chemotherapy induced nausea and vomiting (CINV) is a side effect of a chemotherapy. It contributes mainly to the quality of life during the chemotherapy for cancer treatment. Receptor antagonists can reduce but cannot eliminate the rate of patients suffering from CINV. Some patients are refractory to antiemetic therapy. Aim of our study was to find genomic variations which might contribute as a predictor of a higher risk for CINV

Methods: A prospective consecutive cohort of 82 patients with a primary diagnosis of breast cancer was recruited. All patients received an adjuvant chemotherapy with an anthracyclin. All patients got the same preventive and therapeutic regimen of CINV with 8mg Ondansetron every 8 hours for the first and second day of the chemotherapy cycle. CINV was documented as well as the intake of additional drugs, food and beverages in a structured patient’s diary. Single nucleotide polymorphisms of the 5-HT3-Receptor were analysed. Statistical analysis included development of a cox-model for the development of CINV after the first infusion of chemotherapy.

Results: A total of 53,2% of the patients developed CINV till the end of day 1 of the first chemotherapy cycle. Highest impact on the prediction of the occurrence of CINV had a polymorphism in the 5-HT3-B-Receptor. 34 patients were heterocygote, 39 a homocygote wildtype genotype for the analyzed SNP. 11 patients had a homocygote mutated genotype. Compared to the wildtype status the heterocygote status had a hazard ratio of 1,35 (p=0,027) for the development of CINV.

Conclusion: The efficiency of antiemetic treatment seems to depend on pharmacogenetic determinants. The polymorphic variation in the 5-HT-3-B gene seem to contribute partially to the risk for the development of CINV. Establishing a tool for the prediction of CINV could be the basis for a randomized trial examining the effect of different supportive drugs.