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Chemoptherapy Dose Reductions in Palliative Lung Cancer. Evaluating Chemotherapy Dose Reductions following Neutropenia in Palliative Lung Cancer to prevent further Adverse Events
Amini, Khuram M.A.
Amini, Khuram M.A.
Publication Date
2020
End of Embargo
Rights
The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy and Medical Sciences. Faculty of Life Sciences
Awarded
2020
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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.
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Type
Thesis
Qualification name
PhD