A Tool to Aid in the Safe Administration of Etoposide Containing Regimens in Patients with NHL or Solid Tumors

Abstract

Background: The objective of this study was to develop a new tool (a nomogram) for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients of etoposide-based chemotherapy. \n \nMethods: This retrospective cohort study used the Adverse Drug Events Active Surveillance and Assessment System (ADE-ASAS) to monitor patients with non-Hodgkin s lymphoma (NHL) or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Combined with manual evaluation, neutropenia- or FN-positive cases were identified. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. \n \nResults: A total of 1554 patients were divided into the development group (n=1072) and validation group (n=482). The variables used to predict neutropenia or FN were Karnofsky performance status (KPS) (odds ratio (OR)=0.85, 95% confidence interval (CI)=0.81-0.89, P <0.01), metastatic sites ≥3 (OR=6.33, 95% CI=2.66-15.11,P <0.01), comorbidity of heart disease (OR=4.88, 95% CI=1.74-13.67, P <0.01), recent surgery (OR=7.96, 95% CI=1.96-32.36,P <0.01), administration of alkylating agents (OR=4.50, 95% CI=1.10-18.48, P <0.01), total bilirubin (TBil) ≥25 umol/L (OR=11.42, 95% CI=4.00-32.61, P <0.01), and lymphocyte count <0.7×10 9 /L (OR=4.22, 95% CI=2.00-9.75, P <0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the development group and validation group were 0.93 (95% CI: 0.92-0.95) and 0.90 (95% CI: 0.87-0.92), respectively. The sensitivity and specificity values of this model at the 20% cutoff value were 59.6% (95% CI: 44.3-73.6%) and 98.0% (95% CI: 96.9-98.7%), respectively. \n \nConclusion: A nomogram was developed to predict the risk of neutropenia or FN in the hospitalized population. This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy. \n \nFunding: This research was supported by the Key Project of the Military Medical Innovation Project in 2017 (No. 17CXZ010) and the Special Project for Monitoring and Evaluation of the Use of Clinical Key Drugs commissioned by the Chinese Research Hospital Association (Y2021FH-YWPJ01). \n \nDeclaration of Interest: The authors declare that there are no conflicts of interest. \n \nEthical Approval: The study was approved by the Medical Ethics Committee of PLA General Hospital (No. S2018-54-01).