Importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia.
OBJECTIVE
To assess the value of secondary therapy in the management of high-risk gestational trophoblastic neoplasia (GTN) after failure of initial multiagent chemotherapy.


METHODS
Forty-nine women with high-risk GTN, including 29 who were treated primarily and 20 who were treated secondarily, completed treatment at the Brewer Trophoblastic Disease Center between 1986 and 2010. Initial chemotherapy consisted of etoposide, high-dose methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in 29 patients who were treated primarily and in 10 patients who had received single-agent chemotherapy before being treated at our center. Patients who had incomplete responses or developed resistance to EMA-CO or had previously received EMA-CO were treated with drug combinations employing etoposide and a platinum agent with methotrexate and actinomycin D (EMA-EP), bleomycin (BEP), ifosfamide (VIP, ICE) or paclitaxel (TP/TE). Adjuvant surgery and brain radiation were used in selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.


RESULTS
Twenty-eight (57%) of the 49 patients developed resistance to EMA-CO: 13 (45%) of 29 treated primarily and 15 (75%) of 20 treated secondarily. Of the 13 patients who failed primary treatment with EMA-CO, 10 (77%) had lasting complete responses to EMA-EP (4), BEP (3), VIP (1), ICE (1) or TP/TE (1). Of the 15 patients who failed EMA-CO used as secondary therapy, 13 (87%) had lasting complete responses to EMA-EP (5), BEP (6) or ICE (2). Brain irradiation was given to 4 patients who developed brain metastases during treatment, 3 of whom survived. Operative procedures were performed to remove resistant foci of disease in the lungs (9) or uterus (2) in 11 (39%) of the 28 patients, 9 (82%) of whom survived. Survival was significantly influenced by hCG level at the start of salvage therapy (p<0.001), number of metastatic sites (p <0.02) and metastases to sites other than the lung and vagina (p<0.05).


CONCLUSIONS
Salvage therapy with platinum/etoposide-based drug regimens, often in conjunction with surgery and brain radiation, was successful in achieving cure in 82% of 28 high-risk GTN patients who failed initial multiagent chemotherapy and was ultimately responsible for survival in 53% of the 43 patients (88%) with high-risk GTN who were cured.
John I. Brewer Trophoblastic Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. jlurain@nmff.org
John R
JR
Lurain
Julian C
JC
Schink
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D017671:Platinum Compounds / Q000008:administration & dosage; D011247:Pregnancy; D012307:Risk Factors; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D017671:Platinum Compounds; D001761:Bleomycin; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002955:Leucovorin; D007069:Ifosfamide; D008727:Methotrexate