Gestational trophoblastic neoplasia

Section editor
	Alaina J. Brown, MD, MPH Vanderbilt University Nashville, TN LinkedIn

4 regimens on this page 4 variants on this page

Guidelines

ESMO

• 2013: Seckl et al. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

NCCN

• NCCN Guidelines - Gestational Trophoblastic Neoplasia

Low-risk disease, all lines of therapy

Dactinomycin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Osathanondh et al. 1975	1965-1973	Non-randomized (RT)
Osborne et al. 2011 (GOG 0174)	1999-2007	Phase 3 (E-switch-ic)	Methotrexate	Seems to have superior CR rate
Schink et al. 2020 (GOG 275)	2012-2016	Phase 3 (C)	Methotrexate; multi-day	Did not meet primary endpoint of CR rate

Chemotherapy

• Dactinomycin (Cosmegen) 1.25 mg/m² IV push once on day 1

14-day cycles "until the βhCG assay had reached the institutional normal, or until either a rise or plateau in the βhCG level was observed"

References

1. Osathanondh R, Goldstein DP, Pastorfide GB. Actinomycin D as the primary agent for gestational trophoblastic disease. Cancer. 1975 Sep;36(3):863-6. link to original article PubMed
2. GOG 0174: Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, Provencher D, Scott Miller D, Covens AL, Lage JM. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Mar 1;29(7):825-31. Epub 2011 Jan 24. link to original article link to PMC article contains dosing details in manuscript PubMed Clinical Trial Registry
3. GOG 275: Schink JC, Filiaci V, Huang HQ, Tidy J, Winter M, Carter J, Anderson N, Moxley K, Yabuno A, Taylor SE, Kushnir C, Horowitz N, Miller DS. An international randomized phase III trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia; NRG/GOG 275. Gynecol Oncol. 2020 Aug;158(2):354-360. Epub 2020 May 24. link to original article link to PMC article PubMed Clinical Trial Registry

EMA-CO

EMA-CO: Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Oncovin (Vincristine)

Regimen

Study	Dates of enrollment	Evidence
Newlands et al. 1991	1979-1989	Non-randomized (RT)

Chemotherapy

• Etoposide (Vepesid)
• Methotrexate (MTX)
• Dactinomycin (Cosmegen)
• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)

References

1. Newlands ES, Bagshawe KD, Begent RH, Rustin GJ, Holden L. 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. 1991 Jun;98(6):550-7. link to original article PubMed

Mercaptopurine & Methotrexate

Regimen

Study	Evidence
Li et al. 1958	Pilot

Note: this is of historic interest.

Chemotherapy

• Mercaptopurine (6-MP)
• Methotrexate (MTX)

References

1. Li MC, Hertz R, Bergenstal DM. Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Engl J Med. 1958 Jul 10;259(2):66-74. link to original article PubMed

Methotrexate monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Li et al. 1956	NR	Pilot
Li et al. 1958	1955-1957	Pilot
Homesley et al. 1988	NR in abstract	Phase 2
Osborne et al. 2011 (GOG 0174)	1999-2007	Phase 3 (C)	Dactinomycin	Seems to have inferior CR rate

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

• Methotrexate (MTX) 30 mg/m² IM once on day 1

7-day cycles "until the βhCG assay had reached the institutional normal, or until either a rise or plateau in the βhCG level was observed"

References

1. Li MC, Hertz R, Spencer DB. Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med. 1956 Nov;93(2):361-6. link to original article PubMed
2. Li MC, Hertz R, Bergenstal DM. Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Engl J Med. 1958 Jul 10;259(2):66-74. link to original article PubMed
3. Homesley HD, Blessing JA, Rettenmaier M, Capizzi RL, Major FJ, Twiggs LB. Weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Obstet Gynecol. 1988 Sep;72(3 Pt 1):413-8. link to original article PubMed
4. GOG 0174: Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, Provencher D, Scott Miller D, Covens AL, Lage JM. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Mar 1;29(7):825-31. Epub 2011 Jan 24. link to original article link to PMC article contains dosing details in manuscript PubMed Clinical Trial Registry
5. GOG 275: Schink JC, Filiaci V, Huang HQ, Tidy J, Winter M, Carter J, Anderson N, Moxley K, Yabuno A, Taylor SE, Kushnir C, Horowitz N, Miller DS. An international randomized phase III trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia; NRG/GOG 275. Gynecol Oncol. 2020 Aug;158(2):354-360. Epub 2020 May 24. link to original article link to PMC article PubMed Clinical Trial Registry