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

Ann Oncol. 2010 Aug;21(8):1643-1650. doi: 10.1093/annonc/mdq033. Epub 2010 Feb 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Chorionic Gonadotropin / pharmacokinetics*
  • Drug Resistance, Neoplasm
  • Female
  • Gestational Trophoblastic Disease / drug therapy*
  • Humans
  • Methotrexate / therapeutic use*
  • Pregnancy
  • ROC Curve
  • Retrospective Studies
  • Risk
  • Survival Analysis


  • Antimetabolites, Antineoplastic
  • Chorionic Gonadotropin
  • Methotrexate