A pharmacometrics model to define docetaxel target in early breast cancer
Aims: We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure. Methods: A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles foll...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Wiley
2023
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| Online Access: | https://hdl.handle.net/10171/66083 |
| _version_ | 1793399908514922496 |
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| author | Aldaz, A. (Azucena) Schaiquevich, P. (Paula) Aramendia, J.M. (J.M.) |
| author_facet | Aldaz, A. (Azucena) Schaiquevich, P. (Paula) Aramendia, J.M. (J.M.) |
| author_sort | Aldaz, A. (Azucena) |
| collection | DSpace |
| description | Aims: We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure.
Methods: A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles followed by 4 cycles of docetaxel 75-100 mg/m2 infused every 21 days. Individual Bayesian estimates of docetaxel PK parameters were obtained using a nonparametric population PK model developed with data from patients with metastatic breast cancer who received dose-intensified docetaxel (300-350 mg/m2 ). Docetaxel area under the curve (AUC) and maximum concentration (Cmax) in each cycle and total cumulative AUC (AUCcum) were calculated and related to the incidence of adverse effects and tumour recurrence.
Results: Docetaxel clearance showed no change over the 4 treatment cycles, but a gradual increase in the volume of distribution was observed. One third of the patients had at least 1 dose reduction of docetaxel due to toxicity. The mean AUC, AUCcum and Cmax in patients showing docetaxel-associated adverse events were significantly higher than in patients free of toxicity (P < .05). Fatigue and decrease in haemoglobin and haematocrit levels were related to docetaxel AUC and Cmax and pain to AUC. AUC and Cmax >4.5 mg*h/L and 3.5 mg/L, respectively, were risk factors for docetaxel toxicity, while an AUC <4.5 mg*h/L was associated with tumour recurrence.
Conclusion: We report for the first time a relation between docetaxel exposure and toxicity and recommend specific targets of drug exposure with implications for the clinical management of early breast cancer patients. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-66083 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-660832023-05-01T05:07:10Z A pharmacometrics model to define docetaxel target in early breast cancer Aldaz, A. (Azucena) Schaiquevich, P. (Paula) Aramendia, J.M. (J.M.) Breast cancer Docetaxel Pharmacodynamics Pharmacokinetics Precision medicine Aims: We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure. Methods: A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles followed by 4 cycles of docetaxel 75-100 mg/m2 infused every 21 days. Individual Bayesian estimates of docetaxel PK parameters were obtained using a nonparametric population PK model developed with data from patients with metastatic breast cancer who received dose-intensified docetaxel (300-350 mg/m2 ). Docetaxel area under the curve (AUC) and maximum concentration (Cmax) in each cycle and total cumulative AUC (AUCcum) were calculated and related to the incidence of adverse effects and tumour recurrence. Results: Docetaxel clearance showed no change over the 4 treatment cycles, but a gradual increase in the volume of distribution was observed. One third of the patients had at least 1 dose reduction of docetaxel due to toxicity. The mean AUC, AUCcum and Cmax in patients showing docetaxel-associated adverse events were significantly higher than in patients free of toxicity (P < .05). Fatigue and decrease in haemoglobin and haematocrit levels were related to docetaxel AUC and Cmax and pain to AUC. AUC and Cmax >4.5 mg*h/L and 3.5 mg/L, respectively, were risk factors for docetaxel toxicity, while an AUC <4.5 mg*h/L was associated with tumour recurrence. Conclusion: We report for the first time a relation between docetaxel exposure and toxicity and recommend specific targets of drug exposure with implications for the clinical management of early breast cancer patients. 2023-04-24T09:51:57Z 2023-04-24T09:51:57Z 2023 info:eu-repo/semantics/article https://hdl.handle.net/10171/66083 eng info:eu-repo/semantics/openAccess application/pdf Wiley |
| spellingShingle | Breast cancer Docetaxel Pharmacodynamics Pharmacokinetics Precision medicine Aldaz, A. (Azucena) Schaiquevich, P. (Paula) Aramendia, J.M. (J.M.) A pharmacometrics model to define docetaxel target in early breast cancer |
| title | A pharmacometrics model to define docetaxel target in early breast cancer |
| title_full | A pharmacometrics model to define docetaxel target in early breast cancer |
| title_fullStr | A pharmacometrics model to define docetaxel target in early breast cancer |
| title_full_unstemmed | A pharmacometrics model to define docetaxel target in early breast cancer |
| title_short | A pharmacometrics model to define docetaxel target in early breast cancer |
| title_sort | pharmacometrics model to define docetaxel target in early breast cancer |
| topic | Breast cancer Docetaxel Pharmacodynamics Pharmacokinetics Precision medicine |
| url | https://hdl.handle.net/10171/66083 |
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