EMA/CO for High-Risk Gestational Trophoblastic Tumors
Abstract & Commentary
Synopsis: Etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine is an effective and well-tolerated regimen for high-risk gestational trophoblastic tumor. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.
Source: Bower M, et al. J Clin Oncol 1997;15: 2636-2643.
Bower and associates from charing cross Hospital in London evaluated the results of chemotherapy treatment with etoposide, methotrexate, and dactinomycin alternating with cyclophosphamide and vincristine (EMA/CO) in women with high-risk gestational trophoblastic tumors (GTT) to document the middle- and long-term toxicity of the regimen. They treated a total of 272 consecutive women with high-risk GTT, including 121 previously treated patients, with weekly EMA/CO. The median follow-up duration was 4.5 years (range, 1-16). The cumulative five-year survival rate was 86.2%. No deaths from GTT occurred later than two years after the start of EMA/CO. In a multivariate model, adverse prognostic factors were the presence of liver metastases, interval from antecedent pregnancy, brain metastases, and term delivery of antecedent pregnancy.
There were 11 (4%) early deaths, while 213 patients (78%) achieved a complete remission. Forty-seven women (17%) developed drug resistance to EMA/CO, of whom 33 (70%) were salvaged by further cisplatin-based chemotherapy and surgery. Two women developed acute myeloid leukemia, two women developed cervical malignancy, and one women developed gastric adenocarcinoma after EMA/CO. More than half (56%) of the women who had fertility-conserving surgery and who have been in remission for at least two years have become pregnant since the completion of EMA/CO with 112 live births, including three infants with congenital abnormalities.
Bower et al conclude that EMA/CO is an effective and well-tolerated regimen for high-risk GTT. More than half of the women will retain their fertility; however, there is a small but significant risk of second malignancy.
COMMENT BY DAVID M. GERSHENSON, MD
GTT remains a very rare disease in the United States. Even most large tertiary centers in this country see very few such patients each year. This reported experience from one of the major centers in the world for treatment of GTT is truly remarkable. Based on this work by Kenneth Bagshawe’s group at Charing Cross Hospital, the EMA/CO regimen has also become standard therapy for high-risk GTT patients in the United States.
Several important bits of information emerge from this study. The five-year survival rate of 86.2% is excellent. No patient died more than two years from the start of EMA/CO treatment. The adverse prognostic factors were as one would expect. All 11 early deaths were related to the extent of disease at initiation of chemotherapy. All 11 followed either full-term pregnancy or spontaneous abortionconditions for which careful surveillance is lacking compared with hydatidiform mole.
Among survivors, the most common second malignancy in patients treated for GTT has been myeloid leukemia. Twenty-one women (14%) who had received no prior chemotherapy developed drug resistance to EMA/CO and required a change in therapy; most received platinum-based regimens, and eight also had surgical resections of tumor sites.
Sixteen of the 21 refractory patients (76%) were successfully salvaged with further therapy and were alive and well at the time of this report. The other five patients died of GTT; two of these patients received high-dose chemotherapy with progenitor stem-cell rescue.
Twenty patients who experienced a complete response to EMA/CO later relapsed; six (30%) died of GTT, and 14 (70%) were successfully salvaged with further chemotherapy with or without surgery. More than half of the women who had conservative surgery and were followed for at least two years from the start of EMA/CO therapy became pregnant. Three congenital abnormalities were observed among 112 babies.
As in this country, the investigators recommend that pregnancy is contraindicated for the first year after completion of chemotherapy. In summary, the results with the EMA/CO regimen are laudable, but the second malignancy rate is somewhat concerning.
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