Review
Secondary chemotherapy for high-risk gestational trophoblastic neoplasia

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Abstract

Objective.

To determine the efficacy of secondary chemotherapy after failure of initial treatment for high-risk gestational trophoblastic neoplasia.

Methods

Twenty-six patients with high-risk gestational trophoblastic neoplasia based on WHO criteria who failed primary treatment or relapsed from remission and received secondary chemotherapy were identified from the records of the Brewer Trophoblastic Disease Center. Initial chemotherapy consisted of etoposide, high-dose methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in 10 patients and methotrexate/actinomycin D-based chemotherapy without etoposide in 16 patients. Secondary chemotherapy consisted mainly of platinum-etoposide combinations with methotrexate and actinomycin D (EMA-EP), bleomycin (BEP), or ifosfamide (VIP, ICE). Adjuvant surgery and radiotherapy were used in selected patients. Clinical response and survival as well as factors affecting survival were analyzed retrospectively.

Results

The overall survival has 61.5% (16/26). Of the 10 patients who failed primary treatment with EMA-CO, 9 (90%) had complete clinical responses to secondary chemotherapy with EMA-EP (3) or BEP (6), and 6 (60%) were placed into lasting remission. Of the 16 patients who failed primary treatment with methotrexate/actinomycin D-based chemotherapy without etoposide, 10 (63%) had complete clinical responses to BEP (8), VIP (1) and ICE (1), and 10 (63%) achieved long-term remission. Adjuvant surgical procedures were performed on 15 patients as a component of their therapy; eight (73%) of 11 patients who underwent hysterectomy, five (62%) of eight patients who had pulmonary resections, and one patient who had wedge resection of resistant choriocarcinoma from the uterus survived. Survival was significantly influenced by both hCG level at the start of secondary therapy and sites of metastases.

Conclusion

Patients with persistent or recurrent high-risk gestational trophoblastic neoplasia who develop resistance to methotrexate-containing treatment protocols should be treated with drug combinations employing a platinum agent and etoposide with or without bleomycin or ifosfamide.

Introduction

Since the introduction of pharmacotherapy for the treatment of gestational trophoblastic neoplasia almost 50 years ago, the cure rate for these tumors has steadily increased and now exceeds 90% [1]. It is currently recognized that patients with nonmetastatic (FIGO Stage I) and low-risk metastatic (FIGO Stage II and III, WHO score <7) gestational trophoblastic neoplasia can be treated with single-agent chemotherapy, resulting in a survival rate approaching 100%. Patients with high-risk metastatic disease (FIGO Stage IV or WHO score ≥7) should be treated more aggressively with initial combination chemotherapy with or without adjuvant radiotherapy or surgery to achieve a cure rate of 80%–90%.

Despite this success of chemotherapy in inducing clinical complete responses in most patients with gestational trophoblastic neoplasia, approximately 5% of low-risk patients and 25% of high-risk patients will have an incomplete response to first-line sequential single-agent or multi-agent chemotherapy, respectively, or will relapse from remission. The ultimate cure rate often depends, therefore, on the success of salvage chemotherapy with or without adjuvant surgical procedures. We reviewed the records of the Brewer Trophoblastic Disease Center to determine the efficacy of secondary platinum-based chemotherapy after failure of multi-agent chemotherapy for high-risk gestational trophoblastic neoplasia.

Section snippets

Materials and methods

Twenty-six patients with high-risk gestational trophoblastic neoplasia based on WHO criteria who had failed primary, multi-drug treatment of relapsed from remission and received secondary platinum-based chemotherapy were identified from the records of the John I. Brewer Trophoblastic Disease Center of Northwestern University between 1980 and 2001. Ten patients had failed etoposide, high-dose methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

Results

Of 26 patients with persistent/relapsed high-risk gestational trophoblastic neoplasia who received secondary platinum-based salvage chemotherapy, 19 (73%) had a complete response and 16 (61.5%) survived. Nine (90%) of 10 patients who failed primary treatment with EMA-CO had a complete clinical response to secondary chemotherapy with EMA-EP (3) or BEP (6), and six (60%) were placed into lasting remission (Table 1). Ten (63%) of 16 patients who failed primary treatment with

Discussion

Treatment of low-risk (FIGO Stages I–III, WHO score <7) gestational trophoblastic neoplasia with initial single-agent methotrexate or actinomycin D chemotherapy has resulted in cure of almost all patients [2], [3]. However, approximately 5% of patients with nonmetastatic disease and 10% –15% of patients with low-risk metastatic disease will require multi-agent chemotherapy with or without surgery to achieve remission. The EMA-CO regimen has become the most common secondary chemotherapy used for

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