The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

Comparison of Methotrexate-Folinic Acid versus Pulsed Actinomycin-D in Treatment of Stage I, Low Risk Gestational Trophoblastic Neoplasia: A Randomized Clinical Trial

Document Type : Original Article

Authors
Mehri Jafari Shobeiri 1
Razieh Vejdani 2
Manijeh Sayyah Melli 1
Elaheh Oulad Saheb Madarek 3
Parvin Mostafa Garebaghi 1
Simin Atash khoei 4
Morteza Ghojazadeh 5
Ali Asgharzadeh 6
1 Professor , Department of Gynecological Oncology, Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Iran.
2 Rezident of Obstetrics & Gynecology, Tabriz University of Medical Sciences, Iran.
3 Associate Professor , Department of Gynecological Oncology, Tabriz University of Medical Sciences, Iran.
4 Associate Professor, Department of Anesthesiology, Tabriz University of Medical Sciences, Iran.
5 Associate Professor, Liver & Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Iran.
6 MD & PhD, Student of Molecular Genetic, Tabriz University, Iran.
10.22038/ijogi.2014.2618
Abstract
Introduction: Methotrexate and Actinomycin-D are still used for low risk gestational trophoblastic neoplasia (GTN). The aim of this study was to compare the efficacy and side effects of pulsed Actinomycin-D (ACT-D) and Methotrexate-Folinic Acid (MTX-FA) for Stage I, low-risk gestational trophoblastic neoplasia (GTN).
Methods: This single-blind randomized clinical trial was conducted on 64 patients with stage I, low-risk GTN referred to gynecological oncology clinic of Tabriz University of Medical Sciences, Iran during 2011 and 2012. 32 patients were randomly assigned to receive a pulsed intravenous bolus of ACT-D 1.25 mg/m2 every 2 weeks and 32 patients received an intramuscular Methotrexate 1mg/kg  per day on days 1,3,5,and 7 with intramuscular Folinic Acid 0.1 ml/kg per day on days 2,4,6, and 8. Data were analyzed using SPSS software (version 16) and Fisher exact test, Mann-Whitney U test, independent t-test and chi-square test. P value less than 0.05 was considered significant.
Results: Response to treatment rate were 61.3% (19 patients) for MTX-FA group and 84.85% (28 patients) for ACT-D group (p=0.032). The risk of treatment failure with MTX-FA was 72 times more than ACT-D (p=0.032). The interval between drug administration and response was shorter with ACT-D in compare with MTX-FA (p<0.001). Drug toxicity necessitating changes in chemotherapy was reported in one out of 33 patients only in MTX-FA group. MTX-FA was more cost-effect regimen than ACT-D (p<0.001).
Conclusion: Pulsed ACT-D may be an appropriate option as a first-line chemotherapy agent for patients with stage I, low-risk GTN
Keywords
Actinomycin D
Gestational trophoblastic disease
Methotrexate
  1. Sung HC, Wu PC, Wang YB. Re-evaluation of 5-fluorouracil as a single agent for gestational malignant trophoblastic neoplasms. Adv Exp Med Biol 1984; 176:355-67.
  2. Wong LC, Choo YC, Ma HK. Primary oral etoposide therapy in gestational trophoblastic disease. An update. Cancer 1986 Jul 1; 58 (1): 14-17.
  3. John Soper, William T. Creasman, Gestational trophoblastic disease. In: Philip J. Disaia, William T. Creasman, editors. Clinical Gynecologic Oncology. 7th ed. Philadelphia: Elsevier; 2007. p. 201-233.
  4. 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. Gynecol Oncol 2008 Jan;108(1):149-53. Epub 2007 Oct 10.
  5. 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 Jul; 19(5):985-8.
  6. Alazzam M, Tidy J, Hancock BW, Osborne R. First line chemotherapy in low risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2009 Jan 21;(1):CD007102. Review. 7
  7. ) 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 Xue Za Zhi 2005 Aug 10;85(30):2109-12.
  8. Homesley HD, Blessing JA, Rettenmaier M, Capizzi RL, Major FJ, Twiggs LB. Weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Obstet Gynecol 1988 Sep;72(3 Pt 1):413-8.
  9. Hertz R, Li MC, Spencer DB. Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med 1956 Nov;93(2):361-6.
  10. Li MC. The historical background of successful chemotherapy for advanced gestational trophoblastic tumors. Am J Obstet Gynecol 1979 Sep 15;135(2):266-72.
  11. Lurain JR, Elfstrand. Single-agent methotrexate chemotherapy for the treatment of nonmetastatic gestational trophoblastic tumors. Am J Obstet Gynecol 1995 Feb;172(2 Pt 1):574-9.
  12. Mohit M, Sarraf Z, Sheikhi G, Robati M, Vasheghani-Farahani A. Weekly intramuscular methotrexate in the treatment of low-risk gestational trophoblastic neoplasia. Arch Gynecol Obstet 2009 Nov; 280(5): 775-80. Epub 2009- ar 5.
  13. Bagshawe KD, Wilde CE. Infusion Therapy for pelvic trophoblastic tumours. J Obstet Gynecol Br Commonw 1964 Aug;71:565-70.
  14. Osborne R, Gerulath A. What is the best regimen for low-risk gestational trophoblastic neoplasia? A review. J Reprod Med 2004 Aug;49(8):602-16.
  15. Bagshawe KD, Dent J, Newlands E9, Begent RH, Rustin GJ. The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT). Br J Obstet Gynaecol 1989 Ju1;96(7):795-802.
  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 Dec 15;89(12):2197-201.
  17. Kang WD, Choi HS, Kim SM. Weekly methotrexate (50mg/m(2)) without dose escalation as a primary regimen for low-risk gestational trophoblastic neoplasia. Gynecol Oncol 2010 Jun;117(3):477-80. Epub 2010 Mar 29.
  18. Goldstein DP, Winig P, Shirley RL. Actinomycin D as initial therapy of gestational trophoblastic disease. A reevaluation. Obstet Gynecol 1972 Mar;39(3):341-5.
  19. I. Kohorn. Decision making for chemotherapy administration in patients with low risk gestational trophoblastic neoplasia. International Journal of Gynecological Cancer 1996; 6 (4): 729-85.
  20. Osathanondh R, Goldstein DP, Pastorfide GB. Actinomycin D as the primary agent for gestational trophoblastic disease. Cancer 1975 Sep;36(3):863-6.
  21. Petrilli ES, Morrow CP. Actinomycin D toxicity in the treatment of trophoblastic disease: a comparison of the five-day course to single-dose administration. Gynecol Oncol 1980 Feb;9(1):18- 22.
  22. Petrilli ES, Twiggs LB, Blessing JA, Teng NH, Curry S. Single-dose actinomycin-D treatment for nonmetastatic gestational trophoblastic disease. A prospective phase II trial of the Gynecologic Oncology Group. Cancer 1987 Nov 1;60(9):2173-6.
  23. Yarandi F, Eftekhar Z, Shojaei H, Kanani S, Sharifi A, Hanjani P. Pulse methotrexate versus pulse actinomycin D in the treatment of low-risk gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2008 Oct;103(1):33-7. Epub 2008 Jul 16.
  24. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. FIGO Oncology Committee. Int J Gynaecol Obstet 2002 Jun;77(3):285-7
  25. World Health Organization. Hand Book for reporting results of cancer treatment. WHO offset publication No. 48. Geneva, Switzerland: WHO; 1979:16-21. trophoblastic neoplasia. J Reprod med 1992;36: 49.
  26. Ngan S, Seckl MJ. Gestational trophoblastic neoplasia management: an update. Curr opin oncol 2007; 19(5): 486- 91.
  27. Li M.C., Hertz R. Spencer D.B. Effect of Methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc soc Exp Biol Med 1956; 43: 361-69.
  28. Srisom boon J, Suprasert P, Phongnarisorn C, Treatment results of Methotrexate and folinic acid as primary chemotherapy for non metastatic gestational throphoblastic neoplasia. J Med Assoc Thai 2005; 88: 886-90.
  29. Mcneish IA, Strickland S, Holden L, Rustin GLS, Foskett M, Seckl MJ, et al. Low Risk persistent gestatienal trophoblastic disease: Outcome after intial treatment with low-dose methotrexate and Folinic acid from 1992 to 2000.J clin oncol 2002; 20(7): 1838-44.
  30. Lurain IR, Chapman- Daris E, Hoekstra AV, Schink JC. Actinomycin D for methotreate- failed Low-risk gestational trophoblastic neoplasia. J Reprod Med 2012; 57 (7-8): 283-287.
  31. Chapman- Davis E, Hoskstra AV, Rademaker AW, Schink JC, Lurain JR. Treatment of nonmetastatic and metastatic Low- risk gestational trophoblastic neoplasia: factors associated with resistance to single- agent methotrexate chemotherapy. Gynecal oncol 2012; 125 (3): 572-575. doi: 522-575. doi: 10. 1016/ j. ygyno 2012. 03.039. Epub 2012 Mar 23.