Alternative chemotherapy to EMACO in the treatment of gestational trophoblastic neoplasia

Abstract

The management of GTN is guided by the FIGO risk score ( RS ) which reflects the likelihood of resistance to single agent chemotherapy. While low risk diseases (RS < 7) are usually successfully treated by single agent chemotherapy, combination chemotherapy should be given to those with RS 7 or above. In 1977, Bagshawe reported a 83% sustained remission rate in high-risk GTN with the use of a seven-drug chemotherapy regimen CHAMOMA (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, vincristine, melphalan and doxorubin). After etoposide was shown to be highly effective in the treatment of GTN in the early nineties, the EMA-CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) had been the most popular regime for high risk disease, with an overall survival of around 85% with an acceptable toxicity profile . However, the use of etoposide was subsequently found to be associated with an increased incidence of secondary malignancies, particularly primary leukaemia. In view of the young age of many of our GTN patients, our centre took into account of this risk and adopted the CHAMOC combination, which was modified from on the original CHAMOMA regime, with the removal of melphalan and doxorubicin to reduce toxicity. Twenty-seven year experience ( 1985-2012 ) from our unit suggested that CHAMOC could achieve a 85.3% remission rate, which was comparable to the remission rates reported in literature for EMA-CO. The toxicity profile was also similar. However, no leukaemia was reported in 79 patients treated with CHAMOC at our unit with a median follow up of about 13 years. Our data suggested that CHAMOC could be an alternative to EMA-CO in the primary treatment of high risk GTN. The use of CHAMOC for recurrent disease is also promising but the salvage rate for CHAMOC in the setting of chemo-resistant GTN after single agent chemotherapy appears to be inferior to EMA-CO. If the disease is refractory to EMA-CO/ CHAMOC, salvage with other platinum based regimes such as EMA-EP (EMA alternating weekly with etoposide and cisplatin ) or TE/TP ( paclitaxel and etoposide alternating twice weekly with paclitaxel and cisplatin, with salvage rates over 75% can be considered.