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

Pharm Res. 2019 Oct 15;36(12):163. doi: 10.1007/s11095-019-2697-1.


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.

Keywords: age differences; elderly patients; neutropenia; paclitaxel; pharmacokinetics-pharmacodynamics.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Bone Marrow / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neutropenia / chemically induced*
  • Neutrophils / drug effects
  • Paclitaxel / adverse effects*
  • Retrospective Studies


  • Antineoplastic Agents, Phytogenic
  • Paclitaxel