Clinical Pharmacokinetics

, Volume 45, Issue 6, pp 611–622 | Cite as

Predicting the Toxicity of Weekly Docetaxel in Advanced Cancer

  • Kellie A. Charles
  • Laurent P. Rivory
  • Martin R. Stockier
  • Philip Beale
  • Jane Beith
  • Michael Boyer
  • Stephen J. Clarke
Original Research Article



To determine the safety profile of 40 mg/m2 docetaxel administered weekly to a mixed population of advanced cancer patients and identify predictors of toxicity and survival following treatment with weekly docetaxel in this population.

Patients and methods

68 patients with advanced cancer were enrolled into the study. Various patient characteristics, including inflammatory and nutritional status, docetaxel pharmacokinetics and liver function were investigated. Predictors of treatment-related toxicity and survival were analysed using multivariate logistic regression and Cox proportional hazards analysis, respectively.


27 patients (40%) experienced grade 3 or 4 toxicity, mainly gastrointestinal toxicities (20%), leukopenia (16%) and neutropenia (12%), during the first 8 weeks of docetaxel treatment. Docetaxel pharmacokinetics were the only predictive factor for haematological toxicity. The odds of severe haematological toxicity were approximately 9-fold higher for patients with reduced docetaxel clearance (e.g. <30 L/h). The odds of non-haematological toxicity were about 3-fold higher for patients with elevated levels of inflammatory markers: α1-acid glycoprotein (AAGP) >1.5 g/L or C-reactive protein >10 mg/L). Multivariate analysis indicated that weight loss, liver dysfunction and elevated levels of AAGP were independently significant predictors of survival.


This is the first description of factors predictive of the toxicity and survival following weekly administration of docetaxel. Patients with reduced clearance of docetaxel and elevated markers of inflammation experienced worse adverse effects, while patients with weight loss, liver dysfunction and elevated markers of inflammation had worse survival.


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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Kellie A. Charles
    • 1
  • Laurent P. Rivory
    • 1
    • 2
  • Martin R. Stockier
    • 2
    • 3
  • Philip Beale
    • 2
  • Jane Beith
    • 2
  • Michael Boyer
    • 2
  • Stephen J. Clarke
    • 2
  1. 1.Department of PharmacologyUniversity of SydneySydneyAustralia
  2. 2.Department of Medical Oncology, Level 6 Gloucester HouseSydney Cancer CentreCamperdown, SydneyAustralia
  3. 3.Division of Medicine and School of Public HealthUniversity of SydneySydneyAustralia

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