High-risk Gestational Trophoblastic Tumors Research Articles

Management of High-Risk Gestational Trophoblastic Tumors:

Introduction:Gestational trophoblastic tumors (GTT) are the malignant forms of gestational trophoblastic diseases. They are rare tumors, generally chemosensitive and of excellent prognosis, thus re...

Chemotherapy for high-risk gestational trophoblastic tumors

Primary therapy for high-risk gestational trophoblastic neoplasia (GTN) includes a multi-agent, methotrexate-based regimen, named EMA/CO. In France, the guidelines recommend the use of either a platinum-based protocol when methotrexate is contra-indicated or a highdose EMA/CO once brain metastases are diagnosed. For patients who are resistant to the initial therapy, different salvage approaches have been developed or adapted from treatments already used for germ cell tumors. Currently, the most frequently used protocol is a combination of etoposide and platinum-based therapy (EMA/EP). In the EMA/EP protocol, etoposide and cisplatin are used in place of cyclophosphamide and vincristine (CO in the EMA/CO regimen) with the goal of reversing resistance mechanisms of previously used drugs. Although, new approaches for improving the management of high-risk patients who are resistant or refractory to the initial therapy are now available, new molecules are still awaited to optimize patient’s care.

Etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) for males with HCG-expressing, chemorefractory germ cell tumors (GCT): Long-term efficacy and safety outcomes.

4561 Background: Patients (pts) with GCT who fail to be cured following multiple chemotherapy (CT) courses (including high-dose CT) have an extremely poor prognosis. EMA/CO regimen has shown efficacy in high-risk gestational trophoblastic tumors. Since 1992 we introduced this regimen for human chorionic gonadotropin (HCG)-producing refractory GCT. Methods: We retrieved data of adult male pts who received methotrexate (MTX) 100 mg/m2 followed by MTX 200 mg/m2 over 12h d1, etoposide 100 mg/m2 and dactinomycin 0.5 mg mg/m2 d1-2, folinic acid 15 mg orally every 6h d2-3, followed by cyclophosphamide 600 mg/m2 plus vincristine 1 mg/m2 d8, every 21 days. Treatment was continued until marker normalization. Pts had a HCG+ GCT and had failed at least 2 CT regimens. Multivariable analysis (MVA) was undertaken to analyze candidate prognostic factors. ITT analysis was applied. Results: From 02/92 to 05/13, 41 pts were treated in 3rd (20, 49%) or >3rd line (21, 51%). 36 (88%) had a mixed GCT, 2 a pure seminoma and 3 a ...

Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour.

This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear. To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN. For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN. Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study. We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens. CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.

Erratum: The significance of the time interval between antecedent pregnancy and diagnosis of high-risk gestational trophoblastic tumours

Correction to: British Journal of Cancer (2006) 95, 1145–1147, doi: 10.1038/sj.bjc.6603416 Owing to an error on the author's part, the name of the third author was incorrectly spelt as ‘Sammit’. The correct spelling is now shown above.

The significance of the time interval between antecedent pregnancy and diagnosis of high-risk gestational trophoblastic tumours

It is thought that the time interval between the antecedent pregnancy and diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome of these patients. In this study, we investigate the significance of this time interval. Multivariate analysis was used to investigate if the time interval was of prognostic significance from our cohort of 241 high-risk patients with GTT. Subsequent cutpoint analysis was used to determine an optimal cutpoint for the interval covariate. The outcome of these patients was plotted according to the Kaplan–Meier method. The time interval was of prognostic significance on multivariate analysis. A period of greater than 2.8 years after pregnancy was found to be of most significance. The 5-year overall survival was 62.0% (95% CI: 47–76%) for greater than 2.8 years vs 94% (95% CI: 91–97%) for less than 2.8 years (P<0.001). Multivariate analysis showed the presence of liver metastasis and the number of metastasis was also of prognostic importance. The interval between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic significance. This gives some insight into the pathogenesis of the disease.

Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: A report based on our 11-year clinical experiences

To evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with the 5-fluorouracil (5-FU), methotrexate (MTX) and etoposide (VP-16) regimen. Between 1992 and 2003, 26 consecutive patients with FIGO-defined high-risk GTTs were treated with 5-FU, MTX and VP-16 regimen. Among them, 9 patients had received prior chemotherapy. Remission rate, causes of treatment failure, and toxicity were analyzed retrospectively. After treatment with 5-FU, MTX and VP-16 regimen, 21 of 26 gained complete respond (80.8%). Two patients were performed adjuvant hysterectomy and both cured ultimately. Five developed resistance (19.2%), and 1 died of widespread metastases (3.8%). All 5 patients who developed resistance were treated with multidrug regimen of etoposide, methotrexate, and actionmycin D alternating with cyclophosphamide and vincristine (the EMA/CO); 4 were salvaged and 1 died of refractory disease. No ones relapsed. WHO grade 4 leukocytopenia and thrombocytopenia with the 5-FU, MTX and VP-16 regimen occurred in 9.0% and 2.4%, respectively, of the total 167 cycles; other toxic effects were acceptable and manageable. With mean follow up of 37 months, neither relapse nor secondary tumor was observed. According to our 11 years of clinical observation, 5-FU, MTX and VP-16 chemotherapy is one of effective multiagent regimen for patients with high-risk GTTs. Its toxicity is mild and manageable. For patients with high-risk and refractory GTTs, this new triple salvage chemotherapy regimen may be an effective alternative.

The role of 18F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

We conducted a pilot trial to evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score > or =8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal beta-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n = 2), exclusion of false-positive CT lesions (n = 1), detection of an additional lesion not found by conventional imaging (n = 1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n = 3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. Our preliminary results suggest that 18F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of 18F-FDG PET in GTT.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996-2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17-53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996–2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17–53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.

EMA-EP regimen, as firstline multiple agent chemotherapy in high-risk GTT patients (stage II–IV)

Multiple agent chemotherapy in high-risk metastatic gestational trophoblastic tumor patients is a problem for any medical team. In this study, EMA-EP chemotherapy (etoposide, methotrexate, actinomycin, and cisplatinum) was evaluated as firstline chemotherapy to manage high-risk GTT metastatic patients. Seventeen high-risk metastatic patients, including 14 without and 3 with brain metastasis, who were candidates to firstline multiple agent chemotherapy between April 2000 and March 2003 in Vali-e-Asr hospital took part in a prospective study under EMA-EP regimen. EMA-EP was prescribed in two periods: EMA in two consecutive days in week 1 and EP in 1 day in the following week with a week interval between these two (each cycle was repeated every 2 weeks). In brain metastasis group, patients got high-dose medication (methotrexate) together with brain radiotherapy. Remission, toxicity, full dose tolerance, and recurrences of patients were evaluated. Median age of patients was 30 (15–49), and they received 100 courses of chemotherapy including 75 low-dose courses and 25 high-dose courses. 71% of courses were done in full dosage (83% in low dose and 36% in high dose). The most common cause for dosage reduction was leukopenia. Two patients did not complete the regimen, one due to hypersensitivity and the other due to fever and leukopenia leading to death. All others, who received complete courses, achieved remission. In the group without brain metastasis, one case of recurrence was observed. Grade 3 anemia, grade 3 and 4 leukopenia, and grade 3 and 4 thrombocytopenia were observed in 3, 12, and 3% of patients, respectively. In current study, EMA-EP regimen in patients with high-risk metastatic GTN patients (with or without brain metastasis) lead to remission in all patients who completed the treatment courses.

Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy☆

Objective The objective of the study was to evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia. Methods Forty-five patients with high-risk gestational trophoblastic tumors received 257 EMA-CO treatment cycles between 1986 and 2001. Twenty-five were treated primarily with EMA-CO because of the presence of one or more high-risk factors and 20 were treated with EMA-CO secondarily after failure of single-agent chemotherapy. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing cisplatin and etoposide with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response, and toxicity were analyzed retrospectively. Results The overall survival rates was 91% (41/45); survival rates were 92% (23/25) for primary treatment and 90% (18/20) for secondary treatment with EMA-CO. Of the 45 patients treated with EMA-CO, 32 (71%) had a complete clinical response, 9 (20%) developed resistance but were subsequently placed into remission with cisplatin-based chemotherapy, and 4 (9%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by duration of disease from antecedent pregnancy to treatment (<6 months, 84%, vs >6 months, 43%), metastatic site (lung and pelvis, 73%, vs other, 40%), and WHO score (≤7, 96%, vs >7, 36%). The EMA-CO chemotherapy regimen produced no life-threatening toxicity, caused grade 3–4 hematologic toxicity in 1.6% of cycles, and was associated with neutropenia necessitating a 1-week delay in treatment in only 13.5% of cycles. Conclusions EMA-CO chemotherapy is a well-tolerated and highly effective treatment for high-risk gestational trophoblastic neoplasia, yielding a 71% complete response rate and a 91% survival rate in this series.

Treatment of high-risk gestational trophoblastic tumors.

Treatment of high-risk gestational trophoblastic tumors.

Risk of Abnormal Pregnancy Completing Chemotherapy for Gestational Trophoblastic Tumor

Matsui, Hideo; Iitsuka, Yoshinori; Susuka, Kiyomi; Yamazawa, Koji; Tanaka, Naotake; Seki, Katsuyoshi; Sekiya, Souei

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Objective This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). Methods A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. Results The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) ( P = 0.028). Conclusion Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors.

The objective of this study was to evaluate the efficacy and toxicity of a high-dose 5-fluorouracil and actinomycin D regimen (the FA regimen) as salvage chemotherapy for patients with high-risk gestational trophoblastic tumors (GTTs). From 1985 to 1997, 10 patients with refractory, high-risk GTTs were treated with the FA regimen at Chiba University Hospital. Of those 10 patients, 7 patients developed drug resistance to methotrexate, etoposide, and actinomycin D combination chemotherapy (the MEA regimen); 1 patient developed recurrent disease after receiving the MEA regimen; and 2 patients developed recurrent disease after receiving combination chemotherapy with etoposide, methotrexate, and actinomycin D alternating with cyclophosphamide and vincristine (the EMA/CO regimen). The hematologic toxicity of the FA regimen was graded at every chemotherapy course. With the FA regimen, the survival rate was 80.0% (8 of 10 patients) for a mean follow-up of 10 years. Two patients died due to multidrug resistance, and two patients subsequently developed recurrent disease. The two patients with recurrent disease were successfully salvaged again with the MEA regimen. The toxicity of the FA regimen was evaluated in 78 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidences of World Health Organization Grade 4 leukocytopenia and thrombocytopenia were 6.4% and 3.8%, respectively, of 78 cycles. Although etoposide-containing chemotherapy is currently the most effective and well-tolerated regimen for patients with high-risk GTTs, 20-30% of patients develop resistance to etoposide-containing regimens. Salvage combination chemotherapy with FA is effective for these patients with refractory disease, and the toxicity is predictable and manageable.

Experience of the Gynecologic Oncology Unit at Ain Shams University in the treatment of gestational trophoblastic tumors.

The aim of the study is to evaluate the different treatment modalities in the management of gestational trophoblastic tumors (GTT) in a tertiary care setting. One hundred and twenty patients between 16 and 55 years of age (mean 30.6) diagnosed and treated for GTT at the Gynecologic Oncologic Unit, Ain Shams University, between June 1992 and November 1998 were studied. The mean parity of the group was 2.5 (0-12) with a mean follow-up of 47.4 months (16-96). One hundred cases (83.3%) followed a molar pregnancy, while 17 (14.2%) and three (2.5%) had an antecedent abortion and term pregnancy, respectively. By adopting the National Institutes of Health Classification due to its practicality, 65 (54.1%) were nonmetastatic and 55 (45.9%) were metastatic; 17 (14.2%) low-risk metastatic and 38 (31.7%) high-risk metastatic. Forty-two patients (35%) had a hysterectomy, which was curative in 16 (13.3%). In the high-risk metastatic group, 22 patients were treated with EMA achieving a complete stable remission in 19 (86.3%) with one of the remaining three being salvaged by EMA-EP. One hundred fourteen (95%) patients are alive and well without evidence of disease with all six deaths occurring in the high-risk metastatic group. One of the deaths was due to unrelated disease (repeat variceal hemorrhage from portal hypertension), while the remaining five followed nonmolar pregnancies with four having brain and/or liver metastases and another presenting with resistant fatal acute respiratory distress syndrome (ARDS) despite optimal support. By using multivariate analysis, it was found that only the presence of brain and/or liver metastases, followed by an antecedent nonmolar pregnancy and resistance to multiple agent chemotherapy were significant as regards the prognosis of high-risk metastatic GTT. These tumors are highly curable with death almost limited to those with brain and/or liver metastases, particularly following nonmolar pregnancies. In these extremely high-risk categories, elaboration of more intensive and innovative combination chemotherapy protocols is needed in order to achieve better results than those currently reported. In addition the use of EMA instead of EMA-CO deserves to be tested in properly randomized controlled collaborative studies to reduce treatment toxicity.

Combination Chemotherapy with Methotrexate, Etoposide, and Actinomycin D for High-Risk Gestational Trophoblastic Tumors

Objectives. The goal of this study was to evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with a methotrexate–etoposide–actinomycin D (MEA) regimen without cyclosphosphamide or vincristine.Methods. Thirty-nine consecutive patients with high-risk GTTs (28 were defined high risk by WHO criteria) were treated with primarily the MEA regimen. Among them, 27 patients had received no prior chemotherapy and 12 had received prior chemotherapy. Survival, causes of treatment failure, and toxicity were analyzed retrospectively.Results. After treatment with the MEA regimen, 29 of 39 patients achieved primary remission (74.4%), 8 developed resistance (20.5%), and 2 died of widespread metastases and chemotherapy-related toxicity. All 8 patients who developed resistance were treated with high-dose 5-fluorouracil and actinomycin D (FA); 6 were salvaged and 2 died of refractory disease. Three patients relapsed; 2 were controlled with FA or cisplatin-based chemotherapy and 1 who refused further treatment died. The disease-free survival rate was 87%. WHO grade 4 leukocytopenia and thrombocytopenia with the MEA regimen occurred in 5.3 and 6.4%, respectively, of the cycles; other toxic effects were acceptable and manageable.Conclusions. At present, MEA chemotherapy (without cyclophosphamide or vincristine) is our treatment of choice for patients with high-risk GTT. Its toxicity is predictable and manageable. For patients who become resistant to MEA, new salvage chemotherapy regimens are needed.

Etoposide and Cisplatin/Etoposide, Methotrexate, and Actinomycin D (EMA) Chemotherapy for Patients With High-Risk Gestational Trophoblastic Tumors Refractory to EMA/Cyclophosphamide and Vincristine Chemotherapy and Patients Presenting With Metastatic Placental Site Trophoblastic Tumors

To evaluate the results of etoposide, cisplatin/etoposide, methotrexate, and actinomycin D (EP/EMA) chemotherapy in patients with gestational trophoblastic tumors (GTTs), who have relapsed after or who have become refractory to EMA/cyclophosphamide and vincristine (CO) chemotherapy, and in patients presenting with metastatic placental site trophoblastic tumors (PSTTs). We have treated a total of 34 patients with GTT and eight patients with metastatic PSTT with the EP/EMA chemotherapy schedule. Twenty-two patients received EP/EMA because of apparent drug resistance to EMA/CO, and because the human chorionic gonadotropin (hCG) was near normal, they were not assessable for response. Twenty-one of these patients (95%) are alive and in remission. In the group where the hCG was high enough to confirm a response (greater than one log fall in hCG) to EP/EMA, all 12 patients responded and nine of these patients (75%) are alive and in remission. We have treated three patients with PSTT where the interval from antecedent pregnancy was less than 2 years, and all patients (100%) are alive and in remission. We have treated five patients where the interval from antecedent pregnancy was greater than 2 years and one fifth (20%) remain in remission. The survival for patients with GTT is 30 (88%) out of 34 patients and four (50%) out of eight patients for PSTT, giving an overall survival for these two cohorts of 34 (81%) out of 42 patients. The toxicity of this schedule is significant, with grade 3 or 4 toxicity (National Cancer Institute common toxicity criteria) recorded in hemoglobin (21%), WBC (68%), and platelets (40%). The role of surgery in this group of patients is important and contributed to sustained remission in five patients (23%) and possibly helped an additional seven patients (32%). EP/EMA is an effective but moderately toxic regimen for patients with high-risk GTT who become refractory to or relapse from EMA/CO chemotherapy. Also, EP/EMA clearly has activity in patients with metastatic PSTT.

Risk Factors for the Prediction of Treatment Failure in Gestational Trophoblastic Tumors Treated with EMA/CO Regimen

Objective.The purpose of this study was to determine the independent risk factors for resistance to EMA/CO chemotherapy in gestational trophoblastic tumor (GTT), to develop a more accurate scoring system for the evaluation of high-risk GTT patients.Methods.We performed a retrospective study and reviewed 165 GTT patients who received the EMA/CO regimen. Among these patients, 27 showed resistance to EMA/CO.Results.According to the univariate analysis of risk factors, tumor age, initial human chorionic gonadotropin level, metastatic site, number of metastatic organs, unplanned operation, gravidity, and inadequate previous chemotherapy all showed statistical significance. However, the results of the stepwise–Cox proportional hazards regression of prognostic factors using multivariate analysis showed statistical significance for tumor age, number of metastatic organs, metastatic site, and previously inadequate chemotherapy. The results of the stepwise logistic regression of prognostic factors showed tumor age and number of metastatic organs as significant. According to the performance of the fitted logistic regression model, the accuracy of predicted death and survival was 80.5%.Conclusions.We determined that the following factors indicate a poor prognosis: (1) tumor age greater than 12 months, (2) number of metastatic organs greater 2, (3) incomplete previous treatment, including unplanned operation and inadequate chemotherapy. In patients with two and three of these factors, the death rates were 17.7 and 56.6%, respectively.