Model of Chemotherapy-Induced Myelosuppression With Parameter Consistency Across Drugs
| Autor: | Mats O. Karlsson, Laurent Nguyen, Hugo Maas, Lena E. Friberg, Anja Henningsson |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Paclitaxel Neutrophils medicine.medical_treatment Antineoplastic Agents Docetaxel Irinotecan Vinblastine Deoxycytidine Models Biological Chemotherapy induced Bone Marrow Consistency (statistics) Internal medicine Leukocytes medicine Humans Etoposide Chemotherapy business.industry Predictive factor Immunology Camptothecin Taxoids business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 20:4713-4721 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2002.02.140 |
| Popis: | PURPOSE: To develop a semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs. PATIENTS AND METHODS: Patient leukocyte and neutrophil data after administration of docetaxel, paclitaxel, and etoposide were used to develop the model, which was also applied to myelosuppression data from 2′-deoxy-2′-methylidenecytidine (DMDC), irinotecan (CPT-11), and vinflunine administrations. The model consisted of a proliferating compartment that was sensitive to drugs, three transit compartments that represented maturation, and a compartment of circulating blood cells. Three system-related parameters were estimated: baseline, mean transit time, and a feedback parameter. Drug concentration-time profiles affected the proliferation of sensitive cells by either an inhibitory linear model or an inhibitory Emax model. To evaluate the model, system-related parameters were fixed to the same values for all drugs, which were based on the results from the estimations, and only drug-specific parameters were estimated. All modeling was performed using NONMEM software. RESULTS: For all investigated drugs, the model successfully described myelosuppression. Consecutive courses and different schedules of administration were also well characterized. Similar system-related parameter estimates were obtained for the different drugs and also for leukocytes compared with neutrophils. In addition, when system-related parameters were fixed, the model well characterized chemotherapy-induced myelosuppression for the different drugs. CONCLUSION: This model predicted myelosuppression after administration of one of several different chemotherapeutic drugs. In addition, with fixed system-related parameters to proposed values, and only drug-related parameters estimated, myelosuppression can be predicted. We propose that this model can be a useful tool in the development of anticancer drugs and therapies. |
| Databáze: | OpenAIRE |
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