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Systemic Anti-Cancer Therapy Regimen Library

Home > GYN GTD - EP-EMA [etoposide, ciSplatin - etoposide, metHOTREXATe and daCTINomycin] [high risk]

GYN GTD - EP-EMA [etoposide, ciSplatin - etoposide, metHOTREXATe and daCTINomycin] [high risk]

Treatment Overview

Continuous for 3 cycles beyond normal ß-hCG.


This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycle 1 (and all further cycles) - 14 days

Cycle length:
14

filgrastim: Only two days treatment may be needed with initial cycles (i.e., given on Days 2 and 3, and Days 9 and 10).

Cycle details

Cycle 1 (and all further cycles) - 14 days

Medication Dose Route Days Max Duration
olanzapine * 2.5 mg oral administration 1 to 4
aprepitant 125 mg oral administration 1
aprepitant 80 mg oral administration 2, 3
dexamethasone * 12 mg oral administration 1
dexamethasone * 8 mg oral administration 2, 3, 4,
8, 9, 10
ondansetron 8 mg oral administration 1, 8
etoposide (as phosphate) * 150 mg/m² intravenous 1 60 minutes
magnesium sulfate heptahydrate 10 mmol intravenous 1 60 minutes
cISplatin * 75 mg/m² intravenous 1 60 minutes
sodium chloride 0.9 % intravenous 1 60 minutes
filgrastim 5 microgram/kg Once daily subcutaneous injection 2, 3, 4,
9, 10, 11
sodium chloride 0.9 % intravenous 8 60 minutes
daCTINomycin 0.5 mg flat dosing intravenous 8 5 minutes
etoposide (as phosphate) 100 mg/m² intravenous 8 60 minutes
metHOTREXATe * 300 mg/m² intravenous 8 12 hours
sodium chloride 0.9 % intravenous 8 60 minutes
ondansetron 8 mg oral administration 1, 8
foliNIc acid (as calcium folinate) * 15 mg flat dosing Twice daily oral administration 9, 10
cyclIZINE * 50 mg Three times daily oral administration 1

filgrastim: Only two days treatment may be needed with initial cycles (i.e., given on Days 2 and 3, and Days 9 and 10).

Full details

Cycle 1 (and all further cycles) - 14 days

Day: 1

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONE hour prior to chemotherapy. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
  • Some centres may choose to omit pre-chemotherapy dose or advise patient to take the night before chemotherapy if patient has to drive to appointment.
aprepitant 125 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
dexamethasone * 12 mg oral administration
Instructions:

ONE hour prior to chemotherapy with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
etoposide (as phosphate) * 150 mg/m² intravenous 60 minutes
magnesium sulfate heptahydrate 10 mmol intravenous 60 minutes
Instructions:

In 1000 mL of sodium chloride 0.9%, prior to cisplatin infusion.
cISplatin * 75 mg/m² intravenous 60 minutes
Instructions:
  • In 500 - 1000 mL of sodium chloride 0.9%, depending on stability.
  • Ensure patient has passed urine as per institutional policy.
  • Hypersensitivity risk increases with number of cycles of cisplatin.
sodium chloride 0.9 % intravenous 60 minutes
Quantity:1000 mL
Instructions:

After cisplatin infusion.

  • If cisplatin is infused in 1000 mL, centres may choose to omit this bag of fluid.
ondansetron 8 mg oral administration
Instructions:
EIGHT hours after chemotherapy OR before bed.
cyclIZINE * 50 mg Three times daily oral administration
Instructions:

When required for nausea and/or vomiting.

  • Warning: may cause drowsiness.
  • Consider starting dose at 25 mg and increasing as tolerated/required.
  • The choice of rescue antiemetic may be substituted to reflect institutional policy or individual patient characteristics.
  • Note that domperidone is not recommended in combination with olanzapine and ondansetron due to potential risk of QT prolongation.

Day: 2

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant 80 mg oral administration
Instructions:

ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • Dose and duration may be individualised at clinician’s discretion.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 3

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
aprepitant 80 mg oral administration
Instructions:

ONCE daily in the morning.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • Dose and duration may be individualised at clinician’s discretion.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 4

Medication Dose Route Max duration Details
olanzapine * 2.5 mg oral administration
Instructions:

ONCE daily, regular daily dose. An additional 2.5 mg may be taken daily if required.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • Dose and duration may be individualised at clinician’s discretion.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

This dose may not be needed with initial cycles.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 8

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy with food.
ondansetron 8 mg oral administration
Instructions:

ONE hour prior to chemotherapy.
sodium chloride 0.9 % intravenous 60 minutes
Quantity:1000 mL
Instructions:

Prior to chemotherapy.

  • Ensure patient has passed urine as per institutional policy.
daCTINomycin 0.5 mg flat dosing intravenous 5 minutes
Instructions:
Warning vesicant–ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
etoposide (as phosphate) 100 mg/m² intravenous 60 minutes
metHOTREXATe * 300 mg/m² intravenous 12 hours
sodium chloride 0.9 % intravenous 60 minutes
Quantity:1000 mL
Instructions:

After methotrexate infusion.

  • Ensure patient has passed urine as per institutional policy.
ondansetron 8 mg oral administration
Instructions:
EIGHT hours after chemotherapy OR before bed.

Day: 9

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • This dose may be reduced or omitted at clinician’s discretion.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.
foliNIc acid (as calcium folinate) * 15 mg flat dosing Twice daily oral administration
Instructions:

Every 12 hours for 4 doses commencing 24 hours after start of methotrexate infusion.

  • Take each dose on an empty stomach - one hour before OR two hours after food.

Day: 10

Medication Dose Route Max duration Details
dexamethasone * 8 mg oral administration
Instructions:

ONCE daily in the morning with food.

  • This dose may be reduced or omitted at clinician’s discretion.
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.
foliNIc acid (as calcium folinate) * 15 mg flat dosing Twice daily oral administration
Instructions:

Every 12 hours for 4 doses commencing 24 hours after start of methotrexate infusion.

  • Take each dose on an empty stomach - one hour before OR two hours after food.

Day: 11

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

This dose may not be needed with initial cycles.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Supportive Care Factors

Factor Value
Emetogenicity: Variable
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended

Emetogenicity: HIGH day 1; MEDIUM day 8.

References

LaCasce, Ann S. 2010."Therapeutic use of high-dose methotrexate." In UpToDate. 18.3 Edition. https://www.uptodate.com/contents/therapeutic-use-and-toxicity-of-high-dose-methotrexate

Newlands, E., P. Mulholland, L. Holden, 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 200;18:854-85, PMID: 10673528

Han, S., F. Amant, K. Leunen, et al. 2012. "EP-EMA (Etoposide and Cisplatin with Etoposide, Methotrexate and Dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia" Int J Gynecol Cancer 2012;22:875-880, PMID: 22635033

Ghaemmaghami, F., M. Modares, M. Arab, et al. 2004. "EMA-EP regimen, as firstline multiple agent chemotherapy in high-risk GTT patients (stage II-IV)". Int J Gynecol Cancer 2004;14:360-365, PMID: 15086738

Mao, Y., X. Wan, W. Lv et al. 2007. "Relapsed or refractory gestational trophoblastic neoplasia treated with the etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EP-EMA) regimen". Int J Gynae Obs 2007;98:44-47, PMID: 17481633

Cyriac, S., R. Rajendranath, V. Sridevi, et al. 2011. "Etoposide, cisplatin-etoposide, methotrexate, actinomycin-D as primary treatment for management of very-high-risk gestational trophoblastic neoplasia". Int J Gynaecol Obstet. 2011;115(1):37-9, PMID: 21802685

Boulanger J, Boursiquot JN, Cournoyer G, et al. Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations. Curr Oncol. 2014;21(4):e630-e641., PMID: 25089112

Castells, M.C., Matulonis, U.A., and Horton, TM. Infusion reactions to systemic chemotherapy. Savarese DMF and Feldweg AM, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/infusion-reactions-to-systemic-chemotherapy (Accessed 26 March 2021).

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.