Kantonsspital St.Gallen

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

Marie-Rose B S Crombag, Stijn L W Koolen, Sophie Wijngaard, Markus Joerger, Thomas P C Dorlo, Nielka P Van Erp, Ron H J Mathijssen, Jos H Beijnen & Alwin D R Huitema


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.

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.

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%.

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.
citation Crombag M R B S, Koolen S L W, Wijngaard S, Joerger M, Dorlo T P C, Van Erp N P, Mathijssen R H J, Beijnen J H, Huitema A D R. Does Older Age Lead to Higher Risk for Neutropenia in Patients Treated with Paclitaxel?. Pharm Res 2019; 36:163.
type journal paper/review (English)
date of publishing 15-10-2019
journal title Pharm Res (36/12)
ISSN electronic 1573-904X
pages 163
PubMed 31617004
DOI 10.1007/s11095-019-2697-1