Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia

Prouvot, Catherine; Golfier, François; Massardier, Jérôme; You, Benoît; Lotz, Jean‐Pierre; Patrier, Sophie; Devouassoux, Mojgan; Schott, Anne-Marie; Hajri, Touria; Bolze, Pierre‐Adrien

doi:10.1097/igc.0000000000001248

Cited by 31 publications

(39 citation statements)

References 16 publications

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“…Both datasets stated the appropriate therapeutic effect of the 5-day Act-D salvage therapy on the low-risk GTN patients with MTX failure. To our knowledge, the number of subjects in our study was larger than that in many existing studies on 5-day Act-D salvage therapy in low-risk GTN [3,6,7,15,16,34].…”

Section: Discussionmentioning

confidence: 92%

“…Thus, the possibility of resistance to Act-D salvage therapy increased with increasing serum hCG Act-D level. Gynecological oncologists agree with prescribing Act-D as salvage therapy for patients with low hCG Act-D and EMA-CO for those with high hCG Act-D [3,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Various salvage regimens for cases of primary MTX failure have been described in the literature, including single-agent pulsed actinomycin D (Act-D) [13,14]; 5-day Act-D [1,3,4,7,15,16]; etoposide and Act-D (EA) [17,18]; etoposide, MTX, Act-D/cyclophosphamide, and vincristine (EMA-CO) [1,3,15]; and bleomycin, etoposide and cisplatin (BEP) [19]. Among these regimens, the use of etoposide in multi-agent chemotherapy (e.g., EMA-CO, EA, and BEP) increases the risk of secondary tumors such as leukemia, melanoma, breast cancer, and colon cancer [20].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the Act-D regimen is currently preferred due to its simplicity, limited short-and long-term toxicity, and low risk of carcinogenicity [22][23][24]. However, 5.21%-25.00% of MTX-resistant patients develop Act-D resistance [3,7,[14][15][16] and switch to multi-agent chemotherapy. Some researchers recommended that patients with high levels of serum human chorionic gonadotropin (hCG) at the time of MTX failure be treated directly with multi-agent chemotherapy to reduce drug resistance and shorten the chemotherapy cycle.…”

Section: Introductionmentioning

confidence: 99%

“…However, the definition of high serum hCG level is unclear. In the current literature, high serum hCG levels range from 100-1,000 IU/L [3,[14][15][16]. Identification of an accurate threshold is necessary to determine whether to administer a single-agent Act-D or multiple-agent regimen.…”

Section: Introductionmentioning

confidence: 99%

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The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy

Qin

Shen

et al. 2020

J Gynecol Oncol

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Objective: To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. Methods: This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. Results: The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/ cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG Act-D )in the Act-Dresistant cases were significantly higher than those in the Act-D responders (median 605 vs. 103 IU/L, p=0.009). However, the range of hCG Act-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76-16,664 IU/L vs. 11.43-6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. Conclusion: Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy. The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy

Qin

Shen

et al. 2020

J Gynecol Oncol

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Update on the diagnosis and management of gestational trophoblastic disease

Ngan

Seckl

Berkowitz

et al. 2018

Intl J Gynecology & Obste

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315

198

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Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

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Diagnosis and management of gestational trophoblastic disease: 2021 update

Ngan

Seckl

Berkowitz

et al. 2021

Intl J Gynecology & Obste

Self Cite

154

148

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Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histological type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score ≥7 and Stage IV) is treated with multiagent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent treatment‐resistant tumors.

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Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia

Cited by 31 publications

References 16 publications

The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy

The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy

Update on the diagnosis and management of gestational trophoblastic disease

Diagnosis and management of gestational trophoblastic disease: 2021 update

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