Folic acid versus folinic acid during methotrexate treatment for low-risk gestational trophoblastic neoplasia

To evaluate and compare the treatment results of folinic acid (FA) and folic acid (F) added to the chemotherapy protocol to reduce the toxicity due to methotrexate (MTX) in the treatment of low-risk gestational trophoblastic neoplasia (GTN) patients.

Patients treated for low-risk GTN at two reference centers between January 2000 and March 2023 were included in this retrospective study. Patients were divided into two groups, MTX/FA and MTX/F. Both groups received 50 mg/day MTX on days 1, 3, 5, 7 of treatment. On days 2, 4, 6, 8 of treatment 0.1 mg/kg folinic acid was administered to the MTX/FA group, and 20 mg/day folic acid was administered to the MTX/F group to reduce MTX toxicity. The groups were compared according to treatment success, resistance, and the development of toxicity.

Among 102 low-risk GTN patients included in the study, 64.7% (n = 66) were in the MTX/FA, while the remaining 35.3% (n = 36) were in the MTX/F group. There was no significant difference between MTX/FA and MTX/F groups regarding treatment success, resistance, and toxicity rates (84.8%, 13.6%, 1.6% vs 83.3%, 13.8%, 2.7%), respectively.

Replacement of folinic acid with folic acid in low-risk GTN patients to reduce the toxicity that may develop associated with MTX treatment resulted in similar treatment success rates. Still, no significant change was observed regarding toxicity and resistance. There is a need for comprehensive prospective studies to further elucidate this relationship.