First-line chemotherapy in low-risk gestational trophoblastic neoplasia

Abstract

Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

“…An early criticism of this study was that there are alternative regimens of MTX with higher historic success rates than the 30 mg/m 2 weekly MTX dose used in the trial [3]. All of these historic regimens' success rates have been documented in single center phase II trials [4,5,6,7] and recent single center phase III trials [8,9] with questionable reporting of bias and severe adverse side effects [10]. Importantly, regardless of first agent used, low-risk GTN remains almost completely curable [3].…”

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

“…Rather, the eight-day MTX regimen was compared to a 5-day Act-D regimen (10 mcg/kg D1–5) in a small single-center randomized control trial [9]. There are a multitude of other published first line therapies, all similarly effective with varying side effects, often lacking control groups or adequate reporting of clinical characteristics [10]. …”

“…It is possible that quoted 5-day and 8-day regimen effectiveness data in all of our cited sources is more a reflection of the WHO risk scores included in the cohort of patient's studied rather than the relative effectiveness of the regimen itself. This is a question that GOG 0275 has been designed to answer, and the recent Cochrane meta-analysis also tries to address but does so incompletely given the data available [10]. …”

“…An early criticism of this study was that there are alternative regimens of MTX with higher historic success rates than the 30 mg/m 2 weekly MTX dose used in the trial [3]. All of these historic regimens' success rates have been documented in single center phase II trials [4,5,6,7] and recent single center phase III trials [8,9] with questionable reporting of bias and severe adverse side effects [10]. Importantly, regardless of first agent used, low-risk GTN remains almost completely curable [3].…”

“…However, GOG 0275 has been slow to accrue patients, and many providers persist in using MTX based regimens. Act-D is more costly per dose, has more reported alopecia, mucositis, hematologic toxicity, and in some centers requires centralized access [10]. …”