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International Journal of Clinical Oncology

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01-01-2020 | Methotrexate | Original Article

The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia

Authors: Shizuka Sato, Eiko Yamamoto, Kaoru Niimi, Kazuhiko Ino, Kimihiro Nishino, Shiro Suzuki, Tomomi Kotani, Hiroaki Kajiyama, Fumitaka Kikkawa

Published in: International Journal of Clinical Oncology | Issue 1/2020

Abstract

Objective

This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN).

Methods

Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated.

Results

The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies.

Conclusion

The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.

Lybol C, Thomas CM, Blanken EA et al (2013) Comparing cisplatin-based combination chemotherapy with EMA/CO chemotherapy for the treatment of high risk gestational trophoblastic neoplasia. Eur J Cancer 49(4):860–867. https://doi.org/10.1016/j.ejca.2012.09.015 CrossRefPubMed

Lu WG, Ye F, Shen YM et al (2008) EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients. Int J Gynecol Cancer 18(2):357–362. https://doi.org/10.1111/j.1525-1438.2007.00999.x CrossRefPubMed

Bower M, Newlands ES, Holden L et al (1997) EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. J Clin Oncol 15(7):2636–2643. https://doi.org/10.1200/JCO.1997.15.7.2636 CrossRefPubMed

Kim SJ, Bae SN, Kim JH et al (1998) Risk factors for the prediction of treatment failure in gestational trophoblastic tumors treated with EMA/CO regimen. Gynecol Oncol 71(2):247–253. https://doi.org/10.1006/gyno.1998.5161 CrossRefPubMed

Escobar PF, Lurain JR, Singh DK et al (2003) Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy. Gynecol Oncol 91(3):552–557CrossRef

Soper JT, Evans AC, Clarke-Pearson DL et al (1994) Alternating weekly chemotherapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for high-risk gestational trophoblastic disease. Obstet Gynecol 83(1):113–117PubMed

Newlands ES, Bagshawe KD, Begent RH et al (1991) Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989. Br J Obstet Gynaecol 98(6):550–557CrossRef

Matsui H, Suzuka K, Iitsuka Y et al (2000) Combination chemotherapy with methotrexate, etoposide, and actinomycin D for high-risk gestational trophoblastic tumors. Gynecol Oncol 78(1):28–31. https://doi.org/10.1006/gyno.2000.5813 CrossRefPubMed

Soto-Wright V, Goldstein DP, Bernstein MR et al (1997) The management of gestational trophoblastic tumors with etoposide, methotrexate, and actinomycin D. Gynecol Oncol 64(1):156–159. https://doi.org/10.1006/gyno.1996.4534 CrossRefPubMed

10.

Dobson LS, Lorigan PC, Coleman RE et al (2000) Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease. Br J Cancer 82(9):1547–1552. https://doi.org/10.1054/bjoc.2000.1176 CrossRefPubMedPubMedCentral

11.

Turan T, Karacay O, Tulunay G et al (2006) Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Cancer 16(3):1432–1438. https://doi.org/10.1111/j.1525-1438.2006.00606.x CrossRefPubMed

12.

Committee FO (2002) FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet 77(3):285–287CrossRef

13.

Cole LA, Sutton JM (2004) Selecting an appropriate hCG test for managing gestational trophoblastic disease and cancer. J Reprod Med 49(7):545–553PubMed

14.

Yamamoto E, Niimi K, Fujikake K et al (2016) High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: a case report and literature review. Mol Clin Oncol 5(5):660–664. https://doi.org/10.3892/mco.2016.1011 CrossRefPubMedPubMedCentral

15.

Matsui H, Iitsuka Y, Suzuka K et al (2004) Salvage chemotherapy for high-risk gestational trophoblastic tumor. J Reprod Med 49(6):438–442PubMed

16.

Newlands ES, Mulholland PJ, Holden L et al (2000) Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors. J Clin Oncol 18(4):854–859. https://doi.org/10.1200/JCO.2000.18.4.854 CrossRefPubMed

17.

Wang J, Short D, Sebire NJ et al (2008) Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol 19(9):1578–1583. https://doi.org/10.1093/annonc/mdn181 CrossRefPubMed

18.

Yamamoto E, Niimi K, Shinjo K et al (2014) Identification of causative pregnancy of gestational trophoblastic neoplasia diagnosed during pregnancy by short tandem repeat analysis. Gynecol Oncol Case Rep 9:3–6. https://doi.org/10.1016/j.gynor.2014.04.001 CrossRefPubMedPubMedCentral

19.

Birken S, Maydelman Y, Gawinowicz MA et al (1996) Isolation and characterization of human pituitary chorionic gonadotropin. Endocrinology 137(4):1402–1411. https://doi.org/10.1210/endo.137.4.8625917 CrossRefPubMed

20.

Braunstein GD (2002) False-positive serum human chorionic gonadotropin results: causes, characteristics, and recognition. Am J Obstet Gynecol 187(1):217–224CrossRef

21.

Warne GL, Fairley KF, Hobbs JB et al (1973) Cyclophosphamide-induced ovarian failure. N Engl J Med 289(22):1159–1162. https://doi.org/10.1056/NEJM197311292892202 CrossRefPubMed

22.

Goto S, Ino K, Mitsui T et al (2004) Survival rates of patients with choriocarcinoma treated with chemotherapy without hysterectomy: effects of anticancer agents on subsequent births. Gynecol Oncol 93(2):529–535. https://doi.org/10.1016/j.ygyno.2004.02.018 CrossRefPubMed

23.

Rustin GJ, Booth M, Dent J et al (1984) Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J (Clin Res Ed) 288(6411):103–106CrossRef

24.

Lok CA, van der Houwen C, ten Kate-Booij MJ et al (2003) Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The Netherlands. BJOG 110(6):560–566CrossRef

Title: The efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide and actinomycin D in patients with choriocarcinoma and high-risk gestational trophoblastic neoplasia
Authors: Shizuka Sato
Eiko Yamamoto
Kaoru Niimi
Kazuhiko Ino
Kimihiro Nishino
Shiro Suzuki
Tomomi Kotani
Hiroaki Kajiyama
Fumitaka Kikkawa
Publication date: 01-01-2020
Publisher: Springer Singapore
Keywords: Methotrexate
Methotrexate
Cytostatic Therapy
Published in: International Journal of Clinical Oncology / Issue 1/2020
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-019-01540-9

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Abstract

Objective

Methods

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Conclusion

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