Personalising docetaxel and G-CSF schedules in cancer patients by a clinically validated computational model

O. Vainas, S. Ariad, O. Amir, W. Mermershtain, V. Vainstein, M. Kleiman, O. Inbar, R. Ben-Av, A. Mukherjee, S. Chan, Z. Agur

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background:This study was aimed to develop a new method for personalising chemotherapeutic and granulocyte colony-stimulating factor (G-CSF) combined schedules, and use it for suggesting efficacious chemotherapy with reduced neutropenia.Methods:Clinical data from 38 docetaxel (Doc)-treated metastatic breast cancer patients were employed for validating a new pharmacokinetic/ pharmacodynamics model for Doc, combined with a mathematical model for granulopoiesis. An optimisation procedure was constructed and used for selecting improved treatment schedules.Results:The combined model accurately predicted observed nadir timing (r=0.99), grade 3 or 4 neutropenia (86% success) and neutrophil counts over time in individual patients (r=0.63), and showed robustness to CYP3A-induced variability in Doc clearance. For average patients, the predicted optimal support for the standard chemotherapy regimen, Doc 100 μgm-2 tri-weekly, is G-CSF, 300 g, Q1D × 3, starting day 7 post-Doc. This regimen largely moderates chemotherapy-induced neutrophil nadir and neutropenia duration. The more intensive Doc dose, 150 mgm-2, is optimally supported by the slightly less cost-effective G-CSF 300 g, Q1D × 4, 5 days post-Doc. The latter regimen is optimal for borderline patients (2000 neutrophils per l) under Doc, 100-150 mgm-2 tri-weekly.Conclusions: The new computational method can serve for tailoring efficacious cytotoxic and supportive treatments, minimising side effects to individual patients. Prospective clinical validation is warranted.

Original languageEnglish
Pages (from-to)814-822
Number of pages9
JournalBritish Journal of Cancer
Volume107
Issue number5
DOIs
StatePublished - 21 Aug 2012
Externally publishedYes

Keywords

  • Doc
  • granulocyte colony-stimulating factor
  • mathematical modelling
  • mechanistic PK/PD
  • neutropenia
  • optimisation

Fingerprint

Dive into the research topics of 'Personalising docetaxel and G-CSF schedules in cancer patients by a clinically validated computational model'. Together they form a unique fingerprint.

Cite this