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Does Older Age Lead...
Does Older Age Lead to Higher Risk for Neutropenia in Patients Treated with Paclitaxel?
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Crombag, Marie-Rose B S (author)
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Koolen, Stijn L W (author)
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Wijngaard, Sophie (author)
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Joerger, Markus (author)
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- Dorlo, Thomas P C (author)
- Netherlands Cancer Institute
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van Erp, Nielka P (author)
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Mathijssen, Ron H J (author)
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Beijnen, Jos H (author)
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Huitema, Alwin D R (author)
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(creator_code:org_t)
- 2019-10-15
- 2019
- English.
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 36:12, s. 163-
- Related links:
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https://repub.eur.nl...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- age differences
- elderly patients
- neutropenia
- paclitaxel
- pharmacokinetics-pharmacodynamics
Publication and Content Type
- ref (subject category)
- art (subject category)
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