Etoposide induces complete remission in 56 (95%) of 60 patients with nonmetastatic and low-risk metastatic GTN (76). The use of EMA-CO induced an 83% remission rate in patients with metastasis and a high-risk score (77). Another study confirmed that primary EMA-CO induced complete remission in 76% of the patients with metastatic GTN and a high-risk score (78). Another study reported that EMA-CO induced complete sustained remission in 87 (90.6%) of 96 patients with high-risk (score >6) GTN (79). Remission occurred with EMA-CO in 30 (86%) of 35 patients with brain metastasis (65).
The EMA-CO regimen is well tolerated, and treatment seldom has to be suspended because of toxicity. The EMA-CO regimen is the preferred primary treatment in patients with metastasis and a high-risk prognostic score (score >6).
Patients resistant to EMA-CO can be treated successfully by substituting etoposide and cisplatin on day8 (EMA-EP). EMA-EP induced remission alone or with surgery in 16 (76%) of 21 patients who were resistant to EMA-CO (80).The optimal combination drug protocol will most likely include etoposide, MTX, and ActD and perhaps other agents administered in the most dose-intensive manner.
Efforts continue to identify new agents and regimens effective in treating patients who prove resistant to all standard chemotherapy regimens. A combination of cisplatin, vinblastine, and bleomycin (PVB) was used effectively in patients with drug-resistant tumor (74,75,81). Although ifosfamide and paclitaxel were used successfully, further studies are needed to define their potential role in either primary or second-line therapy (82,83). Osborne et al. reported that a novel three-drug doublet regimen consisting of paclitaxel, etoposide, and cisplatin (TE/TP) induced complete remission in two patients with relapsed high-risk GTN (84). Wan et al. demonstrated that ﬂoxuridine (FUDR)-containing regimens induced complete remission in all of 21 patients with drug-resistant GTN (85). Matsui et al. found that 5-ﬂuorouracil (5-FU) in combination with ActD induced remission in 9 of 11 (82%) patients with drug resistance (86). The potential role for autologous bone marrow transplantation or stem cell rescue in conjunction with ultra-high-dose chemotherapy has yet to be defined, although complete remissions was reported in patients with refractory GTN (87,88).
Duration of Therapy Patients who require combination chemotherapy must be treated intensively to attain remission. Combination chemotherapy should be given as often as toxicity permits until the patient achieves three consecutive normal hCG levels. After normal hCG levels are attained, at least two additional courses of chemotherapy are administered to reduce the risk of relapse.