Individualización posológica de carboplatino en pacientes con cáncer de pulmón no microcítico avanzado
- Autores: Paulo Antonio Silvestre de Faria
- Directores de la Tesis: N. Víctor Jiménez Torres (dir. tes.), Begoña Porta Oltra (dir. tes.), Matilde Merino Sanjuán (dir. tes.)
- Lectura: En la Universitat de València ( España ) en 2010
- Idioma: español
- Tribunal Calificador de la Tesis: Miguel Payá Peris (presid.), Daniel Almenar Cubells (secret.), María Begoña Delgado Charro (voc.), Jorge Manuel Moreira Gonçalves (voc.), Ruy M. Medeiros Melo Silva (voc.)
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- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
Purpose. The Calvert formula is widely applied for a priori dosing of carboplatin based on patients' glomerular filtration rate (GFR). However, in clinical practice the GFR is replaced by an estimate of creatinine clearance calculated by the Cockcroft-Gault (C-G) formula. The goal of this study was to develop a pharmacokinetic model suitable for Bayesian estimation of individual carboplatin clearance in order to establish an individual dose and study the influence of age on the kinetic, dynamic and clinic response of carboplatin in patients with advanced non small cell lung cancer (NSCLC).
Experimental design. Concentration-time data of ultrafiltered platinum and haematological toxicities and clinic information of 34 patients with NSCLC receiving carboplatin day 1 and gemcitabine 1250 mg/m2 days 1 and 8 every 21 days were available. Carboplatin dose was calculated for a foreseen AUC= 5 mg¿min/mL in adults (age<65 years) and AUC= 4 mg¿min/mL in elderly patients (>70 years). Data were described with a linear two-compartment model. The population pharmacokinetic parameters were obtained by means of nonlinear mixed effect modelling approach.
Results. The final covariate model for clearance (L/h) and volume (L) were obtained as follows: TVCL= [4.39-(Age (years)-70)¿0.11+(weight (Kg)-70)¿0.06]; TVVc= [4.79+(weight (kg)-70)¿0.18]. The plasma sample obtained between one and two hours post perfusion gave the best accuracy and precision concentration predictions. Population and individual absolute and relative errors of carboplatin dose calculated in clinical practice indicate that adults and elderly patients are overdosed, 29 and 31%, respectively.
Conclusions. The population pharmacokinetic model developed for carboplatin in patients with advanced NSCLC does not support the general use of the Cockcroft-Gault-Calvert formula, indicating that carboplatin clearance calculated by means of the Cockcroft-Gault-Calvert formula is overestimated, which in turn would have repercussions on dose calculations.
