Gestational trophoblastic neoplasia medical therapy

Template:Choriocarcinoma 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.

Chemotherapy

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

• The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) 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 metastases

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 metastases 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. A variety of regimens have been used with no direct comparisons to determine whether one is superior. Some of the regimens include the following:[1,2] EMA/CO: Etoposide, methotrexate with folinic acid rescue, dactinomycin, cyclophosphamide, and vincristine. This appears to be the most commonly used regimen. EP/EMA: Etoposide and cisplatin with etoposide, methotrexate, and dactinomycin. MAE: Methotrexate with folinic acid rescue, dactinomycin, and etoposide.