Folic acid versus folinic acid during methotrexate treatment for low-risk gestational trophoblastic neoplasia
, 2, 3, 3, 3, 3, 3, 4, 2, 5, 6, 7
Abstract
Objectives: 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.
Material and methods: 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.
Results: 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.
Conclusions: 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.
Keywords: low-risk gestational trophoblastic neoplasiamethotrexatefolinic acidfolic acid
References
- Ngan H, Seckl M, Berkowitz R, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet. 2018; 143(S2): 79–85.
- Seckl M, Sebire N, Berkowitz R. Gestational trophoblastic disease. The Lancet. 2010; 376(9742): 717–729.
- van Trommel NE, Massuger LF, Schijf CP, et al. Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease. J Clin Oncol. 2006; 24(1): 52–58.
- FIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet. 2002; 77(3): 285–287.
- AKGÖL S, OĞLAK S, TUNÇ Ş, et al. Eight-Day Methotrexate/Folinic Acid Regime as Single Agent Chemotherapy for Low-Risk Gestational Trophoblastic Neoplasia: A Retrospective Study. Journal of Clinical Obstetrics & Gynecology. 2022; 32(1): 1–6.
- Maestá I, Nitecki R, Horowitz NS, et al. Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: The New England Trophoblastic Disease Center experience. Gynecol Oncol. 2018; 148(1): 161–167.
- Covens A, Filiaci VL, Burger RA, et al. Gynecologic Oncology Group. Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. Cancer. 2006; 107(6): 1280–1286.
- Islam S, Khan M, Laila K, et al. Efficacy of Folinic Acid in Comparison to Folic Acid for Reducing Side Effects of Methotrexate in Children with Juvenile Idiopathic Arthritis. Open Journal of Pediatrics. 2023; 13(02): 170–180.
- Poli JG, Paiva G, Freitas F, et al. Folinic acid rescue during methotrexate treatment for low-risk gestational trophoblastic neoplasia - How much is just right? Gynecol Oncol. 2021; 162(3): 638–644.
- Shea B, Swinden MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013; 2013(5): CD000951.
- Elm Ev, Altman D, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol . 2008; 61(4): 344–349.
- Carlson V, Walters L, Lambert P, et al. Low-Risk Gestational Trophoblastic Neoplasia in Manitoba: Experience With Alternating Methotrexate and Dactinomycin. Int J Gynecol Cancer. 2018; 28(8): 1448–1452.
- Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). J Natl Cancer Inst. 2014; 106(9): dju244–dju244.
- Maestá I, Nitecki R, Horowitz NS, et al. Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: The New England Trophoblastic Disease Center experience. Gynecol Oncol. 2018; 148(1): 161–167.
- Parker VL, Cushen BF, Hills A, et al. Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia. Gynecol Oncol. 2023; 169: 34–40.
- Shea B, Swinden MV, Ghogomu ET, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol. 2014; 41(6): 1049–1060.
- Straw JA, Szapary D, Wynn WT. Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects. Cancer Res. 1984; 44(7): 3114–3119.
- Greiner PO, Zittoun J, Marquet J, et al. Pharmacokinetics of (-)-folinic acid after oral and intravenous administration of the racemate. Br J Clin Pharmacol. 1989; 28(3): 289–295.
- Pironi L, Cornia GL, Ursitti MA, et al. Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. Int J Clin Pharmacol Res. 1988; 8(2): 143–148.
- Lertkhachonsuk AA, Israngura N, Wilailak S, et al. Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial. Int J Gynecol Cancer. 2009; 19(5): 985–988.
- Khan F, Everard J, Ahmed S, et al. Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects. Br J Cancer. 2003; 89(12): 2197–2201.
- Bagshawe KD, Dent J, Newlands ES, et al. The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT). Br J Obstet Gynaecol. 1989; 96(7): 795–802.
- Berkowitz RS, Goldstein DP, Bernstein MR. Ten year's experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncol. 1986; 23(1): 111–118.
- McNeish IA, Strickland S, Holden L, et al. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol. 2002; 20(7): 1838–1844.
- Sita-Lumsden A, Short D, Lindsay I, et al. Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009. Br J Cancer. 2012; 107(11): 1810–1814.
- Lurain JR, Chapman-Davis E, Hoekstra AV, et al. Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia. J Reprod Med. 2012; 57(7-8): 283–287.
- Covens A, Filiaci VL, Burger RA, et al. Gynecologic Oncology Group. Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. Cancer. 2006; 107(6): 1280–1286.
- Goldstein DP, Berkowitz RS. Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am. 2012; 26(1): 111–131.
