Management of resistant gestational trophoblastic tumors.
OBJECTIVE
To analyze the causes of therapeutic success and failure in the management of patients with high-risk gestational trophoblastic tumors (GTTs).


METHODS
Analysis of 272 consecutive high-risk patients treated at the trophoblastic disease center at the Charing Cross Hospital between 1979 and 1995.


RESULTS
EMA (etoposide, methotrexate, actinomycin D)/CO (cyclophosphamide, vincristine) chemotherapy is our treatment of choice for patients with high-risk GTT. In 272 consecutive patients the cumulative five-year survival was 86.2% (95% confidence interval, 81.9-90.5%). No deaths occurred from GTT more than two years after the start of treatment. In patients whose disease became resistant to EMA/CO or relapsed after receiving EMA/CO, the majority (70%) could be salvaged with further chemotherapy (usually with the EP (etoposide, cisplatin)/EMA chemotherapy with or without surgery. Multivariate analysis identified the following adverse prognostic factors: presence of liver metastases (P < .0001), prolonged interval from antecedent pregnancy (P < .0001), presence of brain metastases (P = .0008) and term delivery of antecedent pregnancy (P = .045). Intensive chemotherapy for treating high-risk GTT carries a small risk of inducing second malignancies, and two patients developed acute myeloid leukemia, 2 cervical malignancy and 1 gastric adenocarcinoma after receiving EMA/CO chemotherapy.


CONCLUSIONS
EMA/CO is an effective and well-tolerated regimen for high-risk GTT. Salvage chemotherapy with EP/EMA is effective in the majority of patients whose disease is resistant to EMA/CO and should be combined with surgery when the dominant site of resistant disease is known. Major adverse prognostic variables have been identified, and patients with combinations of these factors should be considered for innovative therapeutic approaches from the outset.
Newlands
E S
ES
Department of Medical Oncology, Charing Cross Hospital, Middlesex, U.K.
Bower
M
M
Holden
L
L
Short
D
D
Seckl
M J
MJ
Rustin
G J
GJ
Begent
R H
RH
Bagshawe
K D
KD
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D003609:Dactinomycin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D011247:Pregnancy; D012307:Risk Factors; D016896:Treatment Outcome; D014328:Trophoblastic Neoplasms / Q000188:drug therapy*; D014594:Uterine Neoplasms / Q000188:drug therapy*; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002955:Leucovorin; D008727:Methotrexate