A retrospective study to evaluate single agent methotrexate treatment in low risk gestational choriocarcinoma in the United Kingdom

Taylor, Fiona; Short, Dee; Winter, M.C.; Tidy, John; Savage, Philip; Sarwar, Naveed; Hancock, Barry W.; Seckl, Michael J.; Coleman, RE

doi:10.1016/j.ygyno.2014.12.024

Cited by 26 publications

(16 citation statements)

References 24 publications

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“…We identified the predictors of resistance to single-agent treatment in LR GTD by comparing characteristics of the successful treatment group with those of the failed treatment group. Well known predictors of resistance to single-agent chemotherapy in LR GTD include non-molar antecedent pregnancy, choriocarcinoma in pathology, high pretreatment β-hCG levels, and the WHO prognostic score [ 17 18 ]. However, our results showed that a larger tumor size (>3 cm) and a longer duration from the index pregnancy (>2 months) were associated with resistance to single-agent chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease

Lee

Kim

et al. 2017

J Gynecol Oncol

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ObjectiveThe aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D).MethodsWe conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors.ResultsThe complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant.ConclusionBased on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment.

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Section: Discussionmentioning

confidence: 99%

Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease

Lee

Kim

et al. 2017

J Gynecol Oncol

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“…The cure rate of choriocarcinoma and metastatic choriocarcinoma is 80% and about 75%, respectively [2,3]. However, drug resistance in chemotherapy has been reported in recent years, leading to poor outcomes in the clinic, such as recurrence, loss of fertility, or ultimately death [4][5][6]. Therefore, the mechanism underlying choriocarcinoma invasion and resistance needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Role of AhR in regulating cancer stem cell–like characteristics in choriocarcinoma

Tan

et al. 2018

Cell Cycle

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Choriocarcinoma is sensitive to chemotherapy. However, drug resistance has become one of the major problems in recent years. Previous studies have shown that many tumors contained a small fraction of cells that exhibited enhanced tumor initiating potential and stem cell-like properties. It is hypothesized that cancer stem cells (CSCs) are organized in a cellular hierarchy. They also have the qualities of selfrenewal, chemoresistance, and so on. The identification of CSCs in choriocarcinoma and the mechanism contributing to their qualities remain largely unknown. This study focused on the role of AhR, a transcription factor abundantly expressed in many different types of cancer, in the regulation of the expansion of choriocarcinoma CSCs and the exact molecular mechanisms. Spheroid cells isolated from choriocarcinoma in serum-free conditions have stem cell-like characteristics. The expression and nuclear translocation of AhR were markedly elevated in spheroid cells. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly increased the spheroid-forming efficiency, chemotherapy resistance, and ability to form tumor xenografts of the cells, whereas AhR knockdown, using short hairpin RNA (shRNA), dramatically reduced stem cell properties. Mechanistically, activating the β-catenin pathway might be an essential biological function of AhR during the regulation of the CSC characteristics. This study also identified ABCG2, which plays an important role in CSCs, as a direct target of AhR. Together, these results strongly suggested the participation of AhR in choriocarcinoma carcinogenesis. Targeting AhR may provide a novel therapeutic opportunity for choriocarcinoma. ARTICLE HISTORY

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“…In the UK, low chemotherapy rates (5–8%) and high cure rates (98–100%) can be attributed to this successful registration and treatment programme . Patients with trophoblastic disease who meet UK criteria for chemotherapy treatment (Table ) are invited to either Charing Cross Hospital (London) or Weston Park Hospital (Sheffield) for clinical assessment and staging investigations.…”

Section: Introductionmentioning

confidence: 99%

Late spontaneous resolution of persistent molar pregnancy

Taylor

Short

Harvey

et al. 2016

BJOG

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A retrospective study to evaluate single agent methotrexate treatment in low risk gestational choriocarcinoma in the United Kingdom

Cited by 26 publications

References 24 publications

Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease

Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease

Role of AhR in regulating cancer stem cell–like characteristics in choriocarcinoma

Late spontaneous resolution of persistent molar pregnancy

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