Prospective Feasibility Study Of A Predictive Blood Assay To Identify Patients At High Risk Of Chemotherapy-Induced Nausea

6586 Background: Chemotherapy-induced nausea and vomiting (CINV) is a highly feared side effect in patients, possibly affecting nutritional habits, ability to work and motivation to complete regimens. Even with modern interventions, some patients experience moderate to severe nausea. The aim for this study was to identify an objective assessment tool, identifying patients in need of more effective prevention/management of nausea. We hypothesized that a patient’s risk of CINV may reflect individual variations in the efficiency to scavenge free radicals, generated by chemo-induced cell damage in the small intestine, which trigger serotonin release and activates 5-hydroxytryptamine3 (5-HT3) receptors. In considering this hypothesis, we focused our attention on redox homeostasis as maintained by glutathione (GSH), a major antioxidant and free radical scavenger. Methods: Chemotherapy naïve patients diagnosed with lung or colorectal cancers were asked to participate in this IRB-approved study. Consented patients donated a tube of blood (K2 EDTA) and filled out the Rotterdam Symptom Checklist (RSCL) prior to each platinum-based treatment cycle. A commercial kit was used to measure GSH recycling capacity (OxPhos, Rockland Inc.). This assay uses a novel indirect indictor of glutathione-dependent recycling involving conversion of GSH→GSSG→GSH, which releases mercaptoethanol (ME), quantified with dithiobisnitrobenzoic acid (DNTB). Results: Values obtained from the OxPhos assay were normalized to total red blood cell count and compared to self-reported outcomes on the RSCL. Using standard methods we calculated a cut-off for nausea-associated recycling capacity to 1.0, so that < 1.0 indicated development of moderate-to-severe nausea while values > 1.0 were predicted no or mild nausea. Conclusions: Through this approach, we correctly identified 85.7% of patients with an overall sensitivity of 66.7% and specificity of 90.9%. Female patients or patients < 55 years had higher incidence of nausea and were correctly identified in 89% and 73.3% of the cases, respectively. This could be the first objective method to identify patients at high risk of difficult to prevent/manage nausea.