B You1, M Pollet-Villard2, L Fronton3, C Labrousse2, A-M Schott4, T Hajri2, P Girard3, G Freyer5, M Tod3, B Tranchand6, O Colomban3, B Ribba7, D Raudrant2, J Massardier2, S Chabaud8, F Golfier2. 1. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; Medical Oncology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Medical Oncology Department, Drug Development Program, Princess Margaret Hospital, Toronto, Ontario, Canada. Electronic address: benoit.you@laposte.net. 2. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; Gynecology-Obstetrics Department, Hospices Civils de Lyon, Hôtel Dieu, Centre de Référence des Maladies Trophoblastiques, Lyon; Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite. 3. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins. 4. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; EA 4129, Université Lyon 1; Hospices Civils de Lyon, Réseau d'Epidémiologie Clinique International Francophone, Lyon. 5. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; Medical Oncology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. 6. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; Centre Anticancéreux Léon Bérard, Lyon. 7. EA 3738, Université de Lyon, Lyon; Université Lyon 1, Faculté de Médecine Lyon Sud, Oullins; INRIA Grenoble Rhône-Alpes, Montbonnot, Saint Ismier Cedex. 8. Biostatics Department, Unité de Biostatistique et d'évaluation thérapeutique, Centre Anticancereux Léon Bérard, Lyon, France.
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.
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.
Authors: B You; R Harvey; E Henin; H Mitchell; F Golfier; P M Savage; M Tod; M Wilbaux; G Freyer; M J Seckl Journal: Br J Cancer Date: 2013-04-16 Impact factor: 7.640