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Annals of Oncology 21, 8 (2010) 1643-50
Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias.
B. You1, M. Pollet-Villard, L. Fronton, C. Labrousse, A.-M. Schott, T. Hajri, P. Girard2, G. Freyer3, M. Tod, B. Tranchand4, O. Colomban, B. Ribba5, D. Raudrant, J. Massardier6, S. Chabaud, F. Golfier

BACKGROUND: Early identification of patients at high risk for chemoresistance among those treated with methotrexate (MTX) for low-risk gestational trophoblastic neoplasia (GTN) is needed. We modeled human chorionic gonadotropin (hCG) decline during MTX therapy using a kinetic population approach to calculate individual hCG clearance (CL(hCG)) and assessed the predictive value of CL(hCG) for MTX resistance. PATIENTS AND METHODS: A total of 154 patients with low-risk GTN treated with 8-day MTX regimen were retrospectively studied. NONMEM was used to model hCG decrease equations between day 0 and day 40 of chemotherapy. Receiver operating characteristic curve analysis defined the best CL(hCG) threshold. Univariate/multivariate survival analyses determined the predictive value of CL(hCG) and compared it with published predictive factors. RESULTS: A monoexponential equation best modeled hCG decrease: hCG(t) = 3900 x e(-0.149 x t). Median CL(hCG) was 0.57 l/day (quartiles: 0.37-0.74). Only choriocarcinoma pathology [yes versus no: hazard ratio (HR) = 6.01; 95% confidence interval (CI) 2.2-16.6; P < 0.001] and unfavorable CL(hCG) quartile (< or =0.37 versus >0.37 l/day: HR = 6.75; 95% CI 2.7-16.8; P < 0.001) were significant independent predictive factors of MTX resistance risk. CONCLUSION: In the second largest cohort of low-risk GTN patients reported to date, choriocarcinoma pathology and CL(hCG) < or =0.37 l/day were major independent predictive factors for MTX resistance risk.
1 :  HCL - Hospices Civils de Lyon / Centre hospitalier Lyon Sud
2 :  CC IN2P3 - Centre de Calcul de l'inst. national de phy. nucléaire et de phy. des particules
3 :  Université de Lyon
4 :  EA3738 - Ciblage thérapeutique en Oncologie
5 :  ENS Lyon / UCB Lyon / Inria Grenoble Rhône-Alpes - NUMED
6 :  IRC - Institut de recherches sur la catalyse
Informatique/Modélisation et simulation
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