Gestational trophoblastic neoplasia

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Section editor
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 Alaina J. Brown, MD, MPH
Vanderbilt University
Nashville, TN, USA
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4 regimens on this page
6 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO

NCCN

Low-risk, all lines of therapy

Dactinomycin monotherapy

Regimen variant #1, no cap

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 (primary endpoint)

Chemotherapy

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"


Regimen variant #2, capped

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schink et al. 2020 (GOG 275) 2012-2016 Phase 3 (C) Methotrexate; multi-day Did not meet primary endpoint of CR rate

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

Chemotherapy

14-day cycles until hCG values have returned to normal plus 1 cycle

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 NCT00003702
  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 contains dosing details in manuscript PubMed NCT01535053

Mercaptopurine & Methotrexate

Regimen

Study Evidence
Li et al. 1958 Pilot

Note: this is of historic interest.

Chemotherapy

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 variant #1, no escalation

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Li et al. 1956 NR Pilot
Li et al. 1958 1955-1957 Pilot
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

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"


Regimen variant #2, with escalation

Study Dates of enrollment Evidence
Homesley et al. 1988 NR Phase 2

Note: Dose was only escalated if "no major toxicity" was experienced.

Chemotherapy

  • Methotrexate (MTX) as follows:
    • Cycles 1 to 3: 30 mg/m2 IM once on day 1
    • Cycles 4 to 6: 35 mg/m2 IM once on day 1
    • Cycles 7 to 9: 40 mg/m2 IM once on day 1
    • Cycles 10 to 12: 45 mg/m2 IM once on day 1
    • Cycle 13 onwards: 50 mg/m2 IM once on day 1

7-day cycles for 1 cycle past normalization of β-hCG

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 contains dosing details in manuscript 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 NCT00003702
  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 NCT01535053

High-risk, all lines of therapy

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

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
  2. Retrospective: Alifrangis C, Agarwal R, Short D, Fisher RA, Sebire NJ, Harvey R, Savage PM, Seckl MJ. EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol. 2013 Jan 10;31(2):280-6. Epub 2012 Dec 10. link to original article PubMed
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