Abstract P1-11-08: Assay for personalized prediction of chemotherapy-induced delayed nausea

Abstract

Abstract Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect according to patients. CINV can negatively affect nutritional habits, ability to work and motivation to follow treatment regimens. Assessment of CINV is an essential component of care for patients receiving chemotherapy. Multiple factors influence the incidence of CINV with the chemotherapy regimen, both type and dosage, being the primary risk factor. It is generally assumed that the strongest patient-related factors are younger age and female sex. However, reports in the literature have demonstrated that using these factors clinicians underestimate the prevalence of CINV, especially delayed nausea. Thus, there is a need for risk assessment tools to accurately identify patients requiring anti-emetic regimens to improve quality of life of patients and their families. Most chemotherapeutic agents cause bursts of reactive oxygen species (ROS) resulting in cellular damage and release of substances that can activate receptors in the chemoreceptor trigger zone. Glutathione (GSH), a key antioxidant, is responsible for maintaining redox homeostasis by neutralizing ROS elicited from chemotherapy. Therefore, we hypothesized that a patient's risk of CINV may reflect individual variations in the efficiency to scavenge free radicals after chemotherapy. Methods: In our Institutional Review Board approved study, we have enrolled over 300 patients and completed assessment of 133 patients. These patients were treated with highly or moderately emetogenic chemotherapies for lung, colon, or breast cancer. Blood samples were drawn from chemotherapy naïve patients and used to determine the glutathione recycling capacity. The assay detects the conversion of a bioactive probe, hydroxyethyl disulfide, into mercaptoethanol, which once normalized to red blood cell count, indicates glutathione recycling capacity (ChemoTox). Nausea severity was reported using the Rotterdam Symptom Check-List at each treatment cycle. Self-reported symptoms were compared to notes in medical records and anti-emetic prescription history. Results: We previously published the correlation between low ChemoTox and risk of delayed nausea for patients receiving platinum-based therapy for lung and colon cancer (N=64; correctly classified 88.5%; AUC 0.77). In this second evaluation, using SAS/STAT v.14.1 classification trees, we show the results from testing this prediction tool for breast cancer patients that typically are treated with anthracycline- or taxane-based chemotherapies. An early evaluation of anthracycline-based therapies (N=37) demonstrated a weak association between experienced nausea and ChemoTox (correctly classified 69.2%; AUC 0.64). In contrast, patients treated with taxane-based therapies (N=32) demonstrated a similar correlation between ChemoTox and severity of nausea as previously seen for platinum therapies. Also, a similar accuracy in identifying patients at risk of moderate-severe nausea was identified (correctly classified 77.3%; AUC 0.79). Conclusion: The results from our prospective study suggests that a reduced ability to recycle GSH in the blood may offer an objective prediction of delayed nausea, possibly allowing for optimal anti-emetic regimen to improve the quality-of-life for breast cancer patients. Citation Format: McCourt DD, Parikh K, Dadivas A, Brady AL, Kennedy J, Ali ZA, Zeger EL, Shevade A, Gilman PB, Wallon UM. Assay for personalized prediction of chemotherapy-induced delayed nausea [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-08.