First-line chemotherapy in low-risk gestational trophoblastic neoplasia

Abstract

Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.

Trophoblastic Disease Review for Diagnosis and Management: A Joint Report From the International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup

“…Many different schedules have been devised, all of which seem to have activity, but comparison of results is hampered by differences in patient inclusion criteria among other issues. 21 In Europe and many centers internationally, MTX/FA (Table 3) is preferred because it is less toxic. Thus, unlike ActD, it causes no hair loss, induces less nausea and vomiting, and is less myelosuppressive.…”

Low-Risk Gestational Trophoblastic Neoplasia in Manitoba: Experience With Alternating Methotrexate and Dactinomycin

“…There is little consensus worldwide as to the optimal agent and regimen, although methotrexate is favored. 1 Dactinomycin is generally reserved for use as a second-line salvage therapy as it has historically been associated with more severe toxicity. 1,6 Several randomized trials have suggested that dactinomycin is associated with higher complete response rates than methotrexate, without an increase in toxicity.…”

“…1,6 Several randomized trials have suggested that dactinomycin is associated with higher complete response rates than methotrexate, without an increase in toxicity. 1 However, these have been criticized as being underpowered, comparing protocols that are not commonly used worldwide, as well as using weekly methotrexate protocols, which are generally considered less effective than alternate protocols. 7,8 Complete response rates for methotrexate alone are reported between 50% and 85%.…”

“…There are multiple regimens described, with little consensus as to which is optimal. 1 A unique alternating single-agent protocol is used for low-risk GTN at CancerCare Manitoba, Canada. This protocol was adopted from the MD Anderson Cancer Center in Texas, where it was used from 1966 until 1972.…”

Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group–174 Phase III Trial

“…Treatment is usually continued until either normalization of serum human chorionic gonadotrophin (hCG) concentration followed by 1 to 3 additional cycles or resistance to this drug is detected. 1,2 Tumor chemoresistance is frequently characterized as an increase or stagnation of hCG levels during a 2-to 3-week period, but no consensus guideline has been defined. 3 An early assessment of single-agent resistance risk is desirable because it may reduce the likelihood that patients will receive repetitive ineffective chemotherapy cycles.…”