Chemoptherapy Dose Reductions in Palliative Lung Cancer. Evaluating Chemotherapy Dose Reductions following Neutropenia in Palliative Lung Cancer to prevent further Adverse Events

Abstract

Introduction Neutropenia is a life-threatening and dose-limiting toxicity of palliative lung cancer chemotherapy. Whilst some neutropenias are inevitable, evidence suggests that patients with a previous neutropenic event are 50% more likely to have a further neutropenic event. The aim of this research is to evaluate the variables associated with the risk of secondary neutropenic events and the role of chemotherapy dose reductions. Methods A retrospective analysis was carried out on 361 biochemical neutropenic events in palliative lung cancer patients across 5 sites in South Yorkshire and Bassetlaw. Predictors for a secondary neutropenic event were investigated in univariate and multivariate logistic regression analysis. The predictive model was validated through discrimination statistics, described by Receiver Operating Characteristic Area Under Curve (ROC-AUC). Results The incident rate for secondary neutropenic events was 32.7%. Patients with a successful intervention received a higher mean Relative Dose Intensity (RDI) of 75.65% compared to 65.05%, across the 2 chemotherapy cycles. The univariate analysis found that the biochemical type of neutropenia (depth and length of suppression) (p=0.003), dose reduction of drug 1 (p=0.042), average dose reduction (p=0.019), and cumulative dose reduction (p=0.018) were significant at reducing the risk of secondary neutropenia. Granulocyte-Colony Stimulating Factor did not offer a protective effect. The final logistic regression model evaluated 357 events and included all variables due to significant interrelationship. The model had a ROC-AUC of 0.76 (0.71-0.81) (p= 0.0021), explaining 27% of the variance. Conclusion Appropriate dose reductions play a vital role in preventing secondary neutropenic events and delivering optimal RDIs. The results of this study can aid in identifying high-risk patients.