Does Older Age Lead to Higher Risk for Neutropenia in Patients Treated with Paclitaxel?

Autor: Crombag, Marie-Rose B. S., Koolen, Stijn L. W., Wijngaard, Sophie, Joerger, Markus, Dorlo, Thomas P. C., van Erp, Nielka P., Mathijssen, Ron H. J., Beijnen, Jos H., Huitema, Alwin D. R.
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Zdroj: Pharmaceutical Research; Dec2019, Vol. 36 Issue 12, pN.PAG-N.PAG, 1p, 1 Diagram, 2 Charts, 3 Graphs
Abstrakt: Purpose: There is ongoing concern regarding increased toxicity from paclitaxel in elderly patients, particularly of severe neutropenia. Yet, data so far is controversial and this concern is not supported by a clinically relevant age-dependent difference in pharmacokinetics (PK) of paclitaxel. This study assessed whether age is associated with increased risk for paclitaxel-induced neutropenia. Methods: Paclitaxel plasma concentration-time data, pooled from multiple different studies, was combined with available respective neutrophil count data during the first treatment cycle. Paclitaxel pharmacokinetic-pharmacodynamic (PK-PD) data was modeled using a non-linear mixed effects approach and a semiphysiological neutropenia model, where systemic paclitaxel exposure was linked to reduced proliferation of neutrophils. The impact of age was evaluated on relevant variables in the model, using a significance threshold of p < 0.005. Results: Paclitaxel PK-PD data was evaluated from 300 patients, with a median age of 65 years (range 23–84 years), containing 116 patients ≥70 years (39%). First cycle neutrophil counts were adequately described by a threshold effect model of paclitaxel on the proliferation rate of neutrophils. Age as a continuous or dichotomous variable (≥70 versus <70 years) did not significantly impact sensitivity of the bone marrow to paclitaxel nor the average maturation time of neutrophils (both p > 0.005), causing a decline in the respective interindividual variability of <1%. Conclusion: Results from this large retrospective patient cohort do not suggest elderly patients to be at an increased risk of developing paclitaxel-associated neutropenia during the first treatment cycle. Reflexive dose reductions of paclitaxel in elderly patients are unlikely to improve the risk of severe neutropenia and may be deleterious. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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