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 t umors (GTTs). STUDY DESIGN: Analysis of 272 consecutive high-risk pati ents 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 consecuti ve patients the cumulative five-year survival was 86.2 % (95 % confide nce interval, 81.9 - 90.5 %). No deaths occurred from GTT more than tw o years after the start of treatment. In patients whose disease became resistant to EMA/CO or with the EP (etoposide, cisplatin)/EMA chemoth erapy with or without surgery. Multivariate analysis identified the fo llowing adverse prognostic factors: presence of liver metastases (P < .0001), prolonged interval from antecedent pregnancy (P < .0001), pres ence of brain metastases (P = .0008) and term delivery of antecedent p regnancy (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. CONCLUSION: EMA/C O is an effective and well-tolerated regimen for highrisk GTT. Salvage chemotherapy with EP/EMA is effective in the majority of patients who se disease is resistant to EMA/CO and should be combined with surgery when the dominant site of resistant disease is known. Major adverse pr ognostic variables have been identified, and patients with combination s of these factors should be considered for innovative therapeutic app roaches from the outset.