E-ISSN: 2619-9467

Contents    Cover    Publication Date: 22 Mar 2022
Year 2022 - Volume 32 - Issue 1

Open Access

Peer Reviewed

ORIGINAL RESEARCH
1148 Viewed953 Downloaded

Eight-Day Methotrexate/Folinic Acid Regime as Single Agent Chemotherapy for Low-Risk Gestational Trophoblastic Neoplasia: A Retrospective Study

Full Text PDF  
JCOG. 2022;32(1):1-6
DOI: 10.5336/jcog.2021-87522
Article Language: EN
Copyright Ⓒ 2020 by Türkiye Klinikleri. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
ABSTRACT
Objective: To evaluate the 8-day methotrexate (MTX)/folinic acid (FA) as a first-line chemotherapy regimen treatment in terms of complete regression of disease in women with low-risk gestational trophoblastic neoplasia (GTN). Material and Methods: All patients with low-risk GTN treated with an 8-day MTX/FA regimen were retrospectively included in the study. International Federation of Obstetrics and Gynecology and the modified World Health Organization Prognostic Scoring System were used to classify the risk of GTN. All women received diagnostic imaging evaluation before starting the treatment. The same MTX/FA regime was used repeating as a two-week cycle until normalization of the beta-human chorionic gonadotropin (ß-HCG), thus monthly ß-HCG follow-up was scheduled for up to 1 year. Results: Successful treatment was achieved in 56/66 (84.8%) patients. Nine (13.6%) women had resistance and 1 (1.6%) toxicity. The resistance patients were successfully treated with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) protocol, whereas the patient who showed toxicity to the MTX/FA regime was successfully treated with actinomycin-D. Conclusion: Eight-day MTX/FA regime could be useful in low-risk GTN patients with good security margins. The toxicity rates in this protocol were determined as quite low. All resistance was treated successfully with the EMA-CO protocol.
REFERENCES:
  1. Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet. 2010;376(9742):717-29. [Crossref]  [PubMed] 
  2. Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet. 2018;143 Suppl 2:79-85. [Crossref]  [PubMed] 
  3. Chiofalo B, Palmara V, Laganà AS, Triolo O, Vitale SG, Conway F, et al. Fertility sparing strategies in patients affected by placental site trophoblastic tumor. Curr Treat Options Oncol. 2017;18(10):58. [Crossref]  [PubMed] 
  4. van Trommel NE, Massuger LF, Schijf CP, ten Kate-Booij MJ, Sweep FC, Thomas CM. Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease. J Clin Oncol. 2006;24(1):52-8. [Crossref]  [PubMed] 
  5. Li J, Li S, Yu H, Wang J, Xu C, Lu X. The efficacy and safety of first-line single-agent chemotherapy regimens in low-risk gestational trophoblastic neoplasia: A network meta-analysis. Gynecol Oncol. 2018;148(2):247-53. [Crossref]  [PubMed] 
  6. Mousavi A, Cheraghi F, Yarandi F, Gilani MM, Shojaei H. Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease. Int J Gynaecol Obstet. 2012;116(1):39-42. [Crossref]  [PubMed] 
  7. Uberti EM, Fajardo Mdo C, da Cunha AG, Frota SS, Braga A, Ayub AC. Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women. Rev Bras Ginecol Obstet. 2015;37(6):258-65. [Crossref]  [PubMed] 
  8. Hammond CB, Borchert LG, Tyrey L, Creasman WT, Parker RT. Treatment of metastatic trophoblastic disease: good and poor prognosis. Am J Obstet Gynecol. 1973;115(4):451-7. [Crossref]  [PubMed] 
  9. Kanno T, Matsui H, Akizawa Y, Usui H, Shozu M. Treatment results of the second-line chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia treated with 5-day methotrexate and 5-day etoposide. J Gynecol Oncol. 2018;29(6):e89. [Crossref]  [PubMed]  [PMC] 
  10. Carlson V, Walters L, Lambert P, Dean E, Lotocki R, Altman AD. Low-risk gestational trophoblastic neoplasia in manitoba: experience with alternating methotrexate and dactinomycin. Int J Gynecol Cancer. 2018;28(8):1448-1452. [Crossref]  [PubMed] 
  11. Mangili G, Cioffi R, Danese S, Frigerio L, Ferrandina G, Cormio G, et al. Does methotrexate (MTX) dosing in a 8-day MTX/FA regimen for the treatment of low-risk gestational trophoblastic neoplasia affect outcomes? The MITO-9 study. Gynecol Oncol. 2018;151(3):449-52. [Crossref]  [PubMed] 
  12. Lawrie TA, Alazzam M, Tidy J, Hancock BW, Osborne R. First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2016;2016(6):CD007102. [Crossref]  [PubMed]  [PMC] 
  13. Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, et al. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol. 2011;29(7):825-31. [Crossref]  [PubMed]  [PMC] 
  14. Lertkhachonsuk AA, Israngura N, Wilailak S, Tangtrakul S. 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):985-8. [Crossref]  [PubMed] 
  15. Taylor F, Grew T, Everard J, Ellis L, Winter MC, Tidy J, et al. The outcome of patients with low risk gestational trophoblastic neoplasia treated with single agent intramuscular methotrexate and oral folinic acid. Eur J Cancer. 2013;49(15):3184-90. [Crossref]  [PubMed] 
  16. Khan F, Everard J, Ahmed S, Coleman RE, Aitken M, Hancock BW. Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects. Br J Cancer. 2003;89(12):2197-201. [Crossref]  [PubMed]  [PMC] 
  17. Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, 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. [Crossref]  [PubMed]  [PMC] 
  18. Maestá I, Nitecki R, Horowitz NS, Goldstein DP, de Freitas Segalla Moreira M, Elias KM, 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):161-7. [Crossref]  [PubMed] 
  19. Roberts JP, Lurain JR. Treatment of low-risk metastatic gestational trophoblastic tumors with single-agent chemotherapy. Am J Obstet Gynecol. 1996;174(6):1917-23; discussion 1923-4. [Crossref]  [PubMed] 
  20. Bagshawe KD, Dent J, Newlands ES, Begent RH, Rustin GJ. The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT). Br J Obstet Gynaecol. 1989;96(7):795-802. [Crossref]  [PubMed] 
  21. 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):111-8. [Crossref]  [PubMed] 
  22. McNeish IA, Strickland S, Holden L, Rustin GJ, Foskett M, Seckl MJ, 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):1838-44. [Crossref]  [PubMed] 
  23. Sita-Lumsden A, Short D, Lindsay I, Sebire NJ, Adjogatse D, Seckl MJ, 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):1810-4. [Crossref]  [PubMed]  [PMC] 
  24. Covens A, Filiaci VL, Burger RA, Osborne R, Chen MD; 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):1280-6. [Crossref]  [PubMed] 
  25. Goldstein DP, Berkowitz RS. Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am. 2012;26(1):111-31. [Crossref]  [PubMed]