Population Pharmacokinetics and Pharmacokinetically Guided Dosing of Cyclophosphamide, Thiotepa and Carboplatin in High-Dose Chemotherapy.
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| High-dose chemotherapy with peripheral blood progenitor cell transplantation is widely used in the treatment of several malignancies. The combination of cyclophosphamide, thioTEPA and carboplatin (CTC) is one of the most frequently used regimens for solid tumors. High dose chemotherapy is developed as a potentially curative treatment modality but can also cause severe and sometimes life-threatening toxicity. A wide interpatient variability in toxicity is observed, which may be due to variability in the pharmacokinetics of the agents included. We have developed bioanalytical assays for the determination of the agents and their metabolites in blood samples obtained from patients. These methods have been used to study the population pharmacokinetics of cyclophosphamide, thioTEPA, carboplatin and their metabolites in the CTC regiment. Subsequently, relations between toxicity and pharmacokinetics were identified. Based on these relations, strategies have been developed and validated for pharmacokinetically guided dosing of these agents. These methods may avoid (severe) toxicity and prevent underdosing in patients |
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