Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias.

Abstract : 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.
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Annals of Oncology, Oxford University Press (OUP), 2010, 21 (8), pp.1643-50. 〈10.1093/annonc/mdq033〉
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Soumis le : jeudi 22 novembre 2012 - 19:21:38
Dernière modification le : mardi 16 janvier 2018 - 15:41:22

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Benoit You, M. Pollet-Villard, L. Fronton, C. Labrousse, A.-M. Schott, et al.. Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias.. Annals of Oncology, Oxford University Press (OUP), 2010, 21 (8), pp.1643-50. 〈10.1093/annonc/mdq033〉. 〈hal-00756357〉

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