Comparison of Two Therapeutic Regimens: Methotrexate-Folinic Acid (8 days) and Weekly Methotrexate in Patients with Low risk Gestational Trophoblastic neoplasia

Document Type: Original Article

Authors

1 Assistant professor, Fellowship of Gyneco-Oncology, Kerman University of Medical Sciences, Kerman, Iran

2 MD. Obstetrics & Gynecology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background: Methotrexate is used in the treatment of Low-risk Gestational Trophoblastic Neoplasia. The purpose of this study was to compare the therapeutic responses and side effects of two therapeutic methods which were prescribed for patients suffering from Low-risk Gestational Trophoblastic Neoplasia. One method was the daily use of Methotrexate-Folic Acid (for 8 days) and the other was the weekly use of Methotrexate.
Methods:This study is a randomized double-blind clinical trial which was undertaken on 122 patients suffering from Low-risk Gestational Trophoblastic Neoplasia, who referred to AfzaliPoor Hospital in Kerman City, Iran. The patients were randomly divided into two groups: one group took Methotrexate-Folic Acid daily for a period of 8 days (muscular taking of one milligram/kilogram of Methotrexate in days 1,3,5 and 7; and 0.1 milligram/kilogram of Folic Acid in days 2,4,6 and 8); the other group took the same medication weekly (muscular taking of 30 to 50 milligrams per each square meter of body mass every week).
Results: Findings showed that 95% of the patients effectively responded to the 8-day regimen and 90% responded to weekly regimen. Five percent of the 8-day regimen group and 10% of the weekly regimen group needed a second treatment. This difference was not significant. Concerning the related side effects, only one patient in the weekly regimen group experienced nausea and vomiting, and one patient experienced neutropenia; while 4 patients in the 8-day regimen group experienced nausea and vomiting, one patient had mucositis, 2 patients had conjunctivitis, two patients experienced neutropenia, and one patient had thrombocytopenia.
Conclusions: Considering the related costs, the 8-day regimen was significantly more economical and affordable than the weekly regimen.

Keywords


  1. Sung HC, Wu PC, Wang YB. Re-evaluation of 5-fluorouracil as a single agent for gestational malignant trophoblastic neoplasms. AdvExp Med Biol 1984; 176:355-67.
  2. Abrao RA, de Andrade JM, Tiezzi DG, Marana HR, Candido dos Reis FJ, Clagnan WS. Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens. GynecolOncol 2008; 108(1):149-53.
  3. 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.
  4. Alazzam M, Tidy J, Hancock BW, Osborne R. First line chemotherapy in low risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2009; (1):CD007102.
  5. Chen YX, Shen YM, Qian JH, Xie X. Effects of primary chemotherapy with single methotrexate on lowrisk gestational trophoblastic neoplasia and influencing factors thereof. Zhonghua Yi XueZaZhi 2005; 85(30):2109-12. [In Chinese].
  6. Homesley HD, Blessing JA, Rettenmaier M, Capizzi RL, Major FJ, Twiggs LB. Weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. ObstetGynecol 1988; 72(3 Pt 1):413-8.
  7. Hertz R, Li MC, Spencer DB. Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc SocExpBiol Med 1956; 93(2):361-6.
  8. Li MC. The historical background of successful chemotherapy for advanced gestational trophoblastic tumors. Am J ObstetGynecol 1979; 135(2):266-72.
  9. Bagshawe KD, Wilde CE. Infusion Therapy for pelvic trophoblastic tumours. J ObstetGynecol Br Commonw 1964; 71:565-70.
  10. Osborne R, Gerulath A. What is the best regimen for low-risk gestational trophoblastic neoplasia? A review. J Reprod Med 2004; 49(8):602-16.
  11. 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 ObstetGynaecol 1989; 96(7):795-802.
  12. 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.
  13. Kang WD, Choi HS, Kim SM. Weekly methotrexate (50mg/m(2)) without dose escalation as a primary regimen for low-risk gestational trophoblastic neoplasia. GynecolOncol 2010; 117(3):477-80.
  14. Homesley HD, Blessing JA, Schlaerth J, Rettenmaier M, Major FJ. Rapid escalation of weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease: a gynecologic oncology group study. GynecolOncol 1990; 39(3):305-8.
  15. Homesley HD, Blessing JA, Rettenmaier M, Capizzi RL, Major FJ, Twiggs LB. Weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. ObstetGynecol 1988; 72(3 Pt 1):413-8.
  16. Wong LC, Ngan HY, Cheng DK, Ng TY. Methotrexate infusion in low-risk gestational trophoblastic disease. Am J ObstetGynecol 2000; 183(6):1579-82.
  17. Ngan S, Seckl MJ. Gestational trophoblastic neoplasia management: an update. CurrOpinOncol 2007; 19(5):486-91.
  18. Alici S, Eralp Y, Saip P, Argon A, Basaran M, Topuz E, et al. Clinical characteristics of gestational trophoblastic disease at a single institute. Tohoku J ExpMed 2002; 197(2):95-100.
  19. Hoffman MS, Fiorica JV, Gleeson NC, Roberts WS, Cavanagh D. A single institution experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. GynecolOncol1999; 60(2):262-4.
  20. Goldstein DP, Goldstein PR, Bottomley P, Osathanondh R, Marean AR. Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms. ObstetGynecol 1976; 48(3):321-3.
  21. Smith EB, Weed JC Jr, Tyrey L, Hammond CB. Treatment of nonmetastatic gestational trophoblastic disease: results of methotrexate alone versus methotrexate-folinic acid. Am J ObstetGynecol1982; 144 (1):88-92.
  22. Gilani MM, Yarandi F, Eftekhar Z, Hanjani P. Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low-risk gestational trophoblastic neoplasia. Aust N Z J ObstetGynaecol 2005; 45(2):161-4.
  23. Shah NT, Barroilhet L, Berkowitz RS, Goldstein DP, Horowitz N. A cost analysis of first-line chemotherapy for low-risk gestational trophoblastic neoplasia. J Reprod Med 2012; 57(5-6):211-8.