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.
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.
Ann Oncol. 2010 Aug;21(8):1643-1650. doi: 10.1093/annonc/mdq033. Epub 2010 Feb 12.
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.
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.
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.
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.
对于接受甲氨蝶呤（MTX）治疗低危妊娠滋养细胞肿瘤（GTN）的患者，需要早期识别出对化疗耐药的高危患者。我们采用动力学群体方法对 MTX 治疗期间 hCG 下降进行建模，计算个体 hCG 清除率（CL(hCG))，并评估 CL(hCG)对 MTX 耐药的预测价值。
回顾性研究了 154 例接受 8 天 MTX 方案治疗的低危 GTN 患者。NONMEM 用于构建化疗第 0 天至第 40 天 hCG 下降方程。接受者操作特征曲线分析确定最佳 CL(hCG)阈值。单变量/多变量生存分析确定 CL(hCG)的预测价值，并与已发表的预测因素进行比较。
单指数方程最能模拟 hCG 下降：hCG(t)=3900 x e(-0.149 x t)。中位 CL(hCG)为 0.57 l/天（四分位间距：0.37-0.74）。仅绒癌病理[是与否：风险比（HR）=6.01；95%置信区间（CI）2.2-16.6；P<0.001]和不良 CL(hCG)四分位数（<或=0.37 与>0.37 l/天：HR=6.75；95%CI 2.7-16.8；P<0.001）是 MTX 耐药风险的显著独立预测因素。
在迄今为止报道的第二大低危 GTN 患者队列中，绒癌病理和 CL(hCG)<或=0.37 l/天是 MTX 耐药风险的主要独立预测因素。
