Folinic acid rescue during methotrexate treatment for low-risk gestational trophoblastic neoplasia - How much is just right?

Gynecol Oncol. 2021 Sep;162(3):638-644. doi: 10.1016/j.ygyno.2021.07.013. Epub 2021 Jul 13.

Abstract

Objective: To compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with 8-day methotrexate (MTX) with two different regimens of folinic acid (FA).

Methods: Retrospective cohort study of low-risk GTN followed at Rio de Janeiro Federal University, from January/2000-December/2019 with 8-day MTX with FA at 0.1 mg/kg versus 15 mg fixed dose.

Results: Among 667 patients with low-risk GTN, 323 were treated with FA at 0.1 mg/kg and 142 with FA at 15 mg fixed dose. The weight-based and fixed dose groups were comparable in terms of clinical profile but did differ in the hCG pretreatment level (8883 versus 5127 IU/L, p < 0.01) and FIGO risk score 5/6 (3.4% versus 18.3%, p < 0.01), respectively. Despite this, there was no difference in the remission rate in first-line treatment (76.8 versus 81%, p = 0.33), although FA at 0.1 mg/kg had a significantly higher number of chemotherapy cycles to remission (5 versus 4, p < 0.01), need to delay chemotherapy due to toxicity (6.8 versus 2.8%, p < 0.01) and time to remission, (12 versus 8 weeks, p < 0.01), respectively. A logistic regression analysis showed that the different FA rescue regimens appeared comparable in terms of achieving remission in first-line chemotherapy for low-risk GTN (OR:5.16, CI95%:0.84-31.64, p = 0.08).

Conclusion: FA with 15 mg fixed dose as compared to 0.1 mg/kg of FA was associated with similar primary remission rate, relapse or death among low-risk GTN treated with 8-day MTX. This regimen is highly practical, reduces visits to health facilities, appears equally safe and may be preferable with the 8-day MTX regimen in the treatment of low-risk GTN.

Keywords: Chemotherapy; Folinic acid; Gestational trophoblastic neoplasia; Methotrexate; Methotrexate-resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cohort Studies
  • Drug Administration Schedule
  • Female
  • Gestational Trophoblastic Disease / drug therapy*
  • Humans
  • Leucovorin / administration & dosage
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Pregnancy
  • Retrospective Studies
  • Young Adult

Substances

  • Leucovorin
  • Methotrexate