EP-EMA Regimen (Etoposide and Cisplatin With Etoposide, Methotrexate, and Dactinomycin) in a Series of 18 Women With Gestational Trophoblastic Neoplasia

Abstract

Eighteen patients were treated with EP-EMA, either as first-line chemotherapy for high-risk gestational trophoblastic neoplasia (n = 6), placental site trophoblastic tumor (n = 1), or as salvage chemotherapy for gestational trophoblastic neoplasia after single-agent methotrexate (methotrexate, 1 mg/kg, on days 1, 3, 5, and 7 every two weeks) (n = 10) or high-dose methotrexate-etoposide: methotrexate, 1000 mg/m, on day 1; etoposide, 100 mg/m, on days 1 to 2, every week) (n = 1). Median number of cycles of EP-EMA was 8 (range, 3-11). Median follow-up was 19 months (range, 7-77 months). Concerning response rate, 16 patients (89%) achieved complete remission without disease recurrence.Two patients (11%) died: One patient with placental site trophoblastic tumor died of progressive disease; the second patient presented with choriocarcinoma, primarily metastasized to liver, lung, skin, kidney, and brain. She died of sepsis and endocarditis after adding intrathecal methotrexate and switching cisplatin to carboplatin in the EP-EMA regimen. Toxicity was significant. Eight treatment changes were made owing to grade 2 to grade 3 ototoxicity: 7 to high-dose methotrexate-etoposide, 1 change of cisplatin to carboplatin. Fifteen patients (83%) experienced grade 3/4 neutropenia.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

“…• EMA/EP (etoposide, methotrexate, dactinomycin alternating with etoposide and cisplatin) 65,66 or EP/ EMA (etoposide and cisplatin alternating with etoposide, methotrexate, and dactinomycin) 67 • MEA (methotrexate, etoposide, dactinomycin) 68 • MAC (methotrexate, dactinomycin, and chlorambucil) 69 • FA (5-FU and dactinomycin) 70 • MEF (methotrexate, etoposide, and 5-FU) 71 • CHAMOCA (methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine) 69 Due to the lack of RCTs in this setting, systematic reviews have been unable to draw conclusions regarding a superior combination regimen for primary treatment of high-risk GTN. 46,72 EMA/EP (or EP/EMA) is highly active and considered by some to be superior to EMA/CO for ultra-high-risk disease; however, its use as standard initial therapy is limited by increased toxicity and inability to provide adequate salvage chemotherapy if required for persistent/recurrent disease.…”

“…46,72 EMA/EP (or EP/EMA) is highly active and considered by some to be superior to EMA/CO for ultra-high-risk disease; however, its use as standard initial therapy is limited by increased toxicity and inability to provide adequate salvage chemotherapy if required for persistent/recurrent disease. 4,67 Induction Chemotherapy for Ultra-High-Risk Disease Patients with widespread metastatic GTN, as evidenced by a prognostic score .12, have a poorer prognosis. 73,74 Initiation of standard combination chemotherapy in these patients can lead to tumor collapse with hemorrhage, metabolic acidosis, septicemia, and/or multiple organ failure, resulting in the potential for early death (ie, within 4 weeks).…”

Treatment of high-risk gestational trophoblastic neoplasia with weekly high-dose methotrexate–etoposide

“…No grade 3/4 non-haematological toxicity of any kind was observed. This is in strong contrast to the non-haematological toxicity of EP-EMA, with cases of grade 3-4 ototoxicity, neuropathy and anorexia [13,16].…”

“…Of the seven patients previously treated with EP-EMA [13], median serum β-hCG level at start of HD MTX-ETO was average 29,9 IU/l (range 0.1-189); six patients achieved complete remission. The remission rate for the complete group was 83% (10/12 patients).…”

“…Before January 2010, all patients with high risk (WHO score ≥ 7), or patients with low-risk GTN refractory to first-line single agent chemotherapy, were treated primarily with EP-EMA; a subsequent switch to HD MTX-ETO was made when grade ≥ 2 ototoxicity occurred [13]. However, EP-EMA led to important treatment-related toxicity and we changed the first-line multi-agent chemotherapy to HD MTX-ETO since January 2010.…”