Actinomycin D versus etoposide, methotrexate, actinomycin D/cyclophosphamide, and vincristine as second-line treatment in low-risk gestational trophoblastic neoplasia with primary methotrexate resistance.

Authors

Mariza Branco-Silva, Firas Charfare, Ehsan Ghorani, Naveed Sarwar, Baljeet Kaur, Reece Caldwell, Lea Ghataore, Izildinha Maesta, Michael J Seckl

Published in

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. Pages 104904. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

This study assessed the response to second-line actinomycin D or multi-agent etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine in patients with low-risk gestational trophoblastic neoplasia with primary methotrexate resistance.
Patients with low-risk gestational trophoblastic neoplasia who were treated between 2000 and 2022 developing primary methotrexate resistance and subsequently received second-line actinomycin D or etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine were identified from the Charing Cross Gestational Trophoblastic Disease Centre database. Primary methotrexate resistance was defined as a rise in human chorionic gonadotropin after 2 courses or a plateau after 3 courses of methotrexate/folinic acid, while acquired resistance was defined as human chorionic gonadotropin plateau (<10% decrease over 2 courses) or rise (at least 2 values over 2 weeks) after an initial response. The primary outcome was sustained remission (normal human chorionic gonadotropin for 1 year after chemotherapy completion).
Among 1647 women with low-risk gestational trophoblastic neoplasia, 30 developed primary methotrexate resistance. Of these, 7 received actinomycin D and 23 received etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. Clinical characteristics were similar between the groups, except for higher pre-treatment human chorionic gonadotropin levels in the etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine group (median 77,577 vs 286 IU/L, p = .001). Sustained remission rates with second-line therapy alone were 28.6% (2/7) with actinomycin D and 91.3% (21/23) with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (p = .002). Actinomycin D was associated with higher resistance rates (42.9% vs 4.3%, p = .030). Etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine was associated with higher odds of sustained remission (odds ratio 26.25, 95% confidence interval 3.50 to 234.36, p = .003).
Etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine was associated with significantly higher sustained remission rates than actinomycin D as second-line therapy for patients with low-risk gestational trophoblastic neoplasia and primary methotrexate resistance. These findings underscore the importance of distinguishing primary from acquired methotrexate resistance and suggest that etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine should be used from the outset when primary resistance is identified.

PMID:
42618370
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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