Highlights
- •Low hCG levels before high-dose chemotherapy, a favourable prognostic factor.
- •HDC appears to cure a subset of poor-prognosis placental site/epithelioid trophoblastic tumour patients.
- •HDC can salvage a significant proportion of women with refractory choriocarcinoma.
Abstract
Objective
The objective of the study was to evaluate the effect of high-dose chemotherapy (HDC)
with peripheral blood stem cell support (PBSCS) on survival of patients with gestational
trophoblastic neoplasia (GTN) with either refractory choriocarcinomas or a poor-prognosis
placental site/epithelioid trophoblastic tumours (PSTT/ETTs).
Methods
Databases of two referral centres for gestational trophoblastic disease were searched,
and 32 patients treated with HDC between 1994 and 2015 were identified. Tissue samples
were retrieved for genetic evaluation. Cox regression analyses were performed to identify
possible predictors of overall survival (OS).
Results
HDC induced a sustained complete response in 7 patients. Overall, 41% (13/32) of the
patients remained disease free after HDC with or without additional treatment. Patients
who survived had much lower human chorionic gonadotropin (hCG) values (all ≤12 IU/L)
before and after HDC than those who died of disease. Univariable Cox regression analysis
demonstrated that hCG >12 IU/L before or after HDC, International Federation of Gynaecology
and Obstetrics (FIGO) stage II-IV and presence of metastases at the time of diagnosis
were significantly associated with adverse OS. However, only hCG values before HDC
remained significant in a multivariable model (p < 0.001). Five of 11 (45%) patients with PSTT/ETT presenting ≥48 months after antecedent
pregnancy and 6 of 14 (43%) patients with refractory choriocarcinoma were in remission.
Three treatment-related deaths occurred.
Conclusions
Despite 3 treatment-induced deaths, HDC with PBSCS appears to be active in salvaging
selected patients with poor-prognosis PSTT/ETTs and refractory choriocarcinomas. Low
hCG values before HDC seems a beneficial predictor of OS and may suggest that HDC
acts more like a consolidation therapy.
Keywords
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References
- EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis.J Clin Oncol Offi J Am Soc Clin Oncol. 2013; 31: 280-286https://doi.org/10.1200/JCO.2012.43.1817
- Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia.Am J Obstet Gynecol. 2011; 204: 11-18https://doi.org/10.1016/j.ajog.2010.06.072
- Current management of gestational trophoblastic neoplasia.Hematol Oncol Clin N Am. 2012; 26: 111-131https://doi.org/10.1016/j.hoc.2011.10.007
- High-dose chemotherapy and peripheral blood stem cell support in refractory gestational trophoblastic neoplasia.Br J Cancer. 2005; 93: 620-621https://doi.org/10.1038/sj.bjc.6602771
- The multiple myelomas - current concepts in cytogenetic classification and therapy.Nat Rev Clin Oncol. 2018; 15 ([published Online First: 2018/04/25]): 409-421https://doi.org/10.1038/s41571-018-0018-y
- Role of high-dose chemotherapy with autologous stem-cell rescue in men with previously treated germ cell tumors.J Clin Oncol Off J Am Soc Clin Oncol. 2017; 35 ([published Online First: 2016/12/20]): 1036-1040https://doi.org/10.1200/jco.2016.70.6523
- Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.Lancet (London, England). 2009; 374 ([published Online First: 2009/06/26]): 48-55https://doi.org/10.1016/s0140-6736(09)60618-8
- Long-term outcome of placental site trophoblastic tumor in The Netherlands.J Reprod Med. 2013; 58: 224-228
- Risk and prognostic factors in trophoblastic neoplasia.Cancer. 1976; 38 ([published Online First: 1976/09/01]): 1373-1385
- Successful treatment of refractory gestational trophoblastic neoplasm with high-dose etoposide and cyclophosphamide.Gynecol Oncol. 1991; 43 ([published Online First: 1991/12/11]): 317-319
- High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults.Cancer. 1995; 75 ([published Online First: 1995/02/01]): 874-885
- High-dose chemotherapy with autologous bone marrow transplantation for refractory metastatic gestational trophoblastic disease.Gynecol Oncol. 1995; 58: 383-385https://doi.org/10.1006/gyno.1995.1247
- An adolescent case of retroperitoneal pure choriocarcinoma: successful treatment with MCNU-containing high-dose chemotherapy followed by autologous bone marrow transplantation after multiple brain metastases.Pediatr Hematol Oncol. 1996; 13: 167-171
- Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue.Gynecol Oncol. 1997; 65 ([published Online First: 1997/05/01]): 366-369https://doi.org/10.1006/gyno.1997.4677
- Combination of high-dose chemotherapy, autologous bone marrow/peripheral blood stem cell transplantation, and thoracoscopic surgery in refractory nongestational choriocarcinoma of a 45XO/46XY female: a case report.Gynecol Oncol. 1997; 64: 521-525https://doi.org/10.1006/gyno.1996.4598
- Following metastatic placental site trophoblastic tumor with urine beta-core fragment.Gynecol Oncol. 1999; 74: 302-303https://doi.org/10.1006/gyno.1999.5438
- Failure of high-dose chemotherapy with peripheral blood stem cell support for refractory placental site trophoblastic tumor.Gynecol Obstet Investig. 1999; 47 (doi: 10081): 214-216
- Choriocarcinoma and epithelial trophoblastic tumor: successful treatment of relapse with hysterectomy and high-dose chemotherapy with peripheral stem cell support: a case report.Gynecol Oncol. 2002; 85: 204-208https://doi.org/10.1006/gyno.2002.6583
- Experience with platinum-based and high-dose chemotherapy in patients with gestational trophoblastic disease: possible implications for future management.J Canc Res Clin Oncol. 2004; 130: 383-387https://doi.org/10.1007/s00432-004-0568-5
- High-dose chemotherapy with autologous stem cell support as salvage therapy in recurrent gestational trophoblastic disease.Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2013; 23: 1331-1333https://doi.org/10.1097/IGC.0b013e3182a017fc
- High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: a case report and literature review.Mol Clin Oncol. 2016; 5 ([published Online First: 2016/12/03]): 660-664https://doi.org/10.3892/mco.2016.1011
- Survival of women with gestational trophoblastic neoplasia and liver metastases: is it improving?.J Reprod Med. 2012; 57: 262-269
- EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients.J Clin Oncol. 1997; 15: 2636-2643https://doi.org/10.1200/jco.1997.15.7.2636
- Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia.Lancet. 2017; 390 ([published Online First: 2017/12/01]): 2343-2345https://doi.org/10.1016/s0140-6736(17)32894-5
Article info
Publication history
Published online: February 04, 2019
Accepted:
December 23,
2018
Received in revised form:
December 13,
2018
Received:
August 27,
2018
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
