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 μg m(-2) tri-weekly, is G-CSF, 300 μg, Q1D × 3, starting day 7 post-Doc. This regimen largely moderates chemotherapy-induced neutrophil nadir and neutropenia duration. The more intensive Doc dose, 150 mg m(-2), is optimally supported by the slightly less cost-effective G-CSF 300 μg, Q1D × 4, 5 days post-Doc. The latter regimen is optimal for borderline patients (2000 neutrophils per μl) under Doc, 100-150 mg m(-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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Vainas O,Ariad S,Amir O,Mermershtain W,Vainstein V,Kleiman M,Inbar O,Ben-Av R,Mukherjee A,Chan S,Agur Zdoi
10.1038/bjc.2012.316subject
Has Abstractpub_date
2012-08-21 00:00:00pages
814-22issue
5eissn
0007-0920issn
1532-1827pii
bjc2012316journal_volume
107pub_type
杂志文章abstract：:The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary sc...
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