Gestational trophoblastic neoplasia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]

Overview

The mainstay of therapy for choriocarcinoma is chemotherapy.

Medical Therapy

Low-risk gestational trophoblastic neoplasia (FIGO Score 0–6)

• The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG).
• A salvage regimen is instituted if any of the following occur:

• A plateau of the beta-hCG for 3 weeks (defined as a beta-hCG decrease of 10% or less for 3 consecutive weeks)
• A rise in beta-hCG of greater than 20% for 2 consecutive weeks
• Appearance of metastasis

The chemotherapy regimen in the first-line management of low-risk gestational trophoblastic neoplasia (GTN) treatment include the following:

• Preferred regimen(1): Methotrexate 50 mg IM on days 1, 3, 5, and 7 AND folinic acid 7.5 mg PO on days 2, 4, 6, and 8 (most common)
• Preferred regimen(2): Dactinomycin 1.25 mg/m2 IV biweekly pulsed
• Preferred regimen(3): Methotrexate 30 mg/m2 IM weekly
• Alternative regimen(1): Methotrexate 1 mg/kg IM days 1, 3, 5, and 7 AND folinic acid 0.1 mg/kg IM days 2, 4, 6, and 8
• Alternative regimen(2): Methotrexate 20 mg/m2 IM days 1 to 5, repeated every 14 days
• Alternative regimen(3): Dactinomycin 12 μg/kg/day IV days 1 to 5, repeated every 2 to 3 weeks
• Alternative regimen(4): Methotrexate 20 mg IM daily, days 1 to 5 AND dactinomycin 500 μg IV daily, days 1 to 5, repeated every 14 days
• Alternative regimen(5): Dactinomycin 10 μg/kg/day, days 1 to 5, repeated every 2 weeks
• Alternative regimen(6): Methotrexate 0.4 mg/kg/day IM daily on days 1 to 5, repeated after 7 days
• Alternative regimen(7): Etoposide 100 mg/m2/day IV on days 1 to 5 OR 250 mg/m2 IV on days 1 and 3, at 10-day intervals

High-risk gestational trophoblastic neoplasia (FIGO Score ≥7) Treatment

• Preferred regimen: EMA/CO (i.e., etoposide, methotrexate, and dactinomycin/cyclophosphamide and vincristine) is the most commonly used regimen.
• The specifics are provided in table below.

Day	Drug	Dose
1	Etoposide	100 mg/m2 IV for 30 min
	Dactinomycin	0.5 mg IV push
	Methotrexate	300 mg/m2 IV for 12 h
2	Etoposide	100 mg/m2 IV for 30 min
	Dactinomycin	0.5 mg IV push
	Folinic Acid	15 mg or PO every 12 h × 4 doses, beginning 24 h after the start of methotrexate
8	Cyclophosphamide	600 mg/m2 IV infusion
	Vincristine	0.8–1.0 mg/m2 IV push (maximum dose 2 mg

Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastasis present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles.

• Alternative regimen(1): MAC: Methotrexate AND folinic acid AND dactinomycin AND cyclophosphamide
• Alternative regimen(2): Another MAC: Methotrexate AND dactinomycin AND chlorambucil
• Alternative regimen(3): EMA: Etoposide AND methotrexate AND folinic acid AND dactinomycin (EMA/CO without the CO)
• Alternative regimen(4): CHAMOCA: Methotrexate AND dactinomycin AND cyclophosphamide AND doxorubicin AND melphalan AND hydroxyurea AND vincristine
• Alternative regimen(5): CHAMOMA: Methotrexate AND folinic acid AND hydroxyurea AND dactinomycin AND vincristine AND melphalan AND doxorubicin

Brain metastasis

• Systemic methotrexate as part of the EMA component (i.e., etoposide, methotrexate, folinic acid, and dactinomycin) /CO (1 g/m2 IV for 24 hours, followed by folinic-acid rescue, 15 mg PO q6h for 12 doses starting 32 hours after methotrexate).
• Patients with brain metastasis received an increased dose of systemic methotrexate of 1 g/m2 for 24 hours followed by folinic acid (15 mg PO q6h for 12 doses starting 32 hours after methotrexate).

Placental Site Trophoblastic Tumor Treatment

• Tumors confined to the uterus (Féderation Internationale de Gynécologie et d’Obstétrique [FIGO] Stage I)

• Hysterectomy is the treatment of choice

• Tumors with extrauterine spread to genital structures (FIGO stage II)

• Complete resection with or without adjuvant chemotherapy

• Metastatic tumors (FIGO stages III and IV)

• Polyagent chemotherapy
• EMA/CO: Etoposide AND methotrexate with folinic acid rescue AND dactinomycin AND cyclophosphamide AND vincristine(most common)
• EP/EMA: Etoposide AND cisplatin AND etoposide AND methotrexate AND dactinomycin
• MAE: Methotrexate with folinic acid rescue AND dactinomycin AND etoposide