Increasing the human chorionic gonadotrophin cut-off to ≤1000 IU/l for starting actinomycin D in post-molar gestational trophoblastic neoplasia developing resistance to methotrexate spares more women multi-agent chemotherapy

Background: A human chorionic gonadotropin (hCG) cut-off of <= 300 IU/l for starting actinomycin D (ActD) in post-molar gestational trophoblastic neoplasia (GTN) patients developing methotrexate resistance (MTX-R) reduced the number of women needing toxic multi-agent chemotherapy (etoposide, MTX and ActD alternating weekly with cyclophosphamide and vincristine; EMA/CO) without affecting survival. Here we assess whether an increased hCG cut-off of <= 1000 IU/l spares more women EMA/CO. Patients and methods: All post-molar GTN patients treated with first-line methotrexate and folinic acid (MTX/FA) were identified in a national cohort between 2009 and 2016. Data collected included age, FIGO score, the hCG levels at MIX-R, and treatment outcomes. Results: In total, 609 GTN patients commenced treatment with MTX/FA achieving a complete response in 57% (348/609). Resistance developed in 25.1% (153/609) at an hCG <= 1000 IU/l and switching to ActD achieved remission in 92.8% without any major toxicity with the remaining 7.2% remitting on EMA/CO. Comparative analysis of patients switching at an hCG <100 versus 100-300 versus 300-1000 IU/l revealed a significant fall in the cure rate with second-line ActD from 97% (93/96) to 87% (34/39) to 78% (14/18), respectively, P = 0.009. However, by increasing the hCG cut-off from <= 300 to <= 1000 IU/l, 14 patients were spared EMA/CO chemotherapy. Moreover, in the present series, all post-molar GTN remain in remission. Conclusion: This study demonstrates that increasing the hCG cut-off from <= 300 to <= 1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.

Automated summary

Increasing the hCG cut-off from <= 300 to <= 1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.