Therapeutic drug monitoring for dose individualization of Cisplatin in testicular cancer patients based upon total platinum measurement in plasma
| Autor: | Sébastien Salas, Suzanne Monjanel-Mouterde, Alain Durand, Cédric Mercier, Roger Favre, Charlotte Dupuis, Chenguang Yang, Marjorie Baciuchka-Palmaro, Joseph Ciccolini, Bruno Lacarelle, Bertrand Pourroy, Raphaelle Fanciullino, Medhi Balti, Florence Duffaud, Brigitte Tranchand |
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| Přispěvatelé: | Vidalin, Michèle, Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral - UMR 6032 (CISMET), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Université de la Méditerranée - Aix-Marseille 2 |
| Rok vydání: | 2006 |
| Předmět: |
Male
Body Surface Area Pharmacology Kidney Kidney Function Tests 030226 pharmacology & pharmacy 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Pharmacology (medical) Infusion Pumps Body surface area education.field_of_study medicine.diagnostic_test Middle Aged 3. Good health 030220 oncology & carcinogenesis [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Drug Monitoring Algorithms Leydig Cell Tumor Adult medicine.medical_specialty Metabolic Clearance Rate Digestive System Diseases Population Cmax Antineoplastic Agents Drug Administration Schedule 03 medical and health sciences Pharmacokinetics Testicular Neoplasms medicine Humans education Aged Retrospective Studies Models Statistical Dose-Response Relationship Drug business.industry Kidney metabolism Bayes Theorem Survival Analysis Surgery NONMEM Therapeutic drug monitoring Pharmacodynamics [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Cisplatin business |
| Zdroj: | Therapeutic Drug Monitoring Therapeutic Drug Monitoring, 2006, 28(4), pp.532-9 Therapeutic Drug Monitoring, Lippincott, Williams & Wilkins, 2006, 28(4), pp.532-9 |
| ISSN: | 0163-4356 |
| Popis: | Cisplatin (CDDP) is an anticancer agent widely used in testicular cancer, for which pharmacokinetic (PK)/pharmacodynamic relationships have usually been based upon measurement of its unbound fraction in plasma. Because it has been shown that free CDDP clearance can be related to patient's body surface area (BSA), dosage is mostly adjusted a priori using only this single parameter, with mixed results for accurately predicting CDDP exposure and reducing toxicities. In contrast, the authors present here an original, 5-day continuous infusion schedule, coupled to a daily Bayesian adaptive dosing with feedback strategy, based upon the rapid assay of total, rather than free, CDDP in plasma. Nineteen patients (66 therapeutic courses) were treated with platinum-based combinational therapy. Plasma samples were analyzed to allow real-time Bayesian estimation of individual PK parameters with subsequent prospective dose adjustment in order to reach a target Cmax (Cend) of 1.95 mg/L of total platinum. Performance of the Bayesian dosing method was evaluated by comparing target Cmax with achieved Cmax. The mean+/-SD Cmax achieved was 1.93+/-0.16 mg/L. No statistically significant difference was observed between experimental and target values (P>0.05, t test), and Cend achievement was done with an overall 6.6% precision, a performance to be compared with the initial 54% interpatient variability observed in CDDP clearance. A nonlinear mixed effect model population PK analysis was subsequently performed to identify retrospectively the covariates associated with PK parameters of total CDDP. It showed a good correlation (r=0.84, P=0.004) between total platinum clearance and therapeutic course number. A weaker correlation (r=0.59) was found between BSA and total CDDP clearance and, importantly, no additional relationship was established with BSA when successive therapeutic courses, and not only the first one, were considered. This highlights the critical importance of total drug accumulation on CDDP pharmacokinetics when several infusions are to be administered in a row and, therefore, the need for real-time dose individualization that takes into account the course number, rather than BSA. Finally, doses of CDDP administered during each course were significantly higher (+20%, P |
| Databáze: | OpenAIRE |
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