VP-16 in combinations for first-line treatment of malignant germ-cell tumors and gestational choriocarcinoma.

VP-16 (VePesid) was incorporated into combinations for first-line treatment of patients with malignant germ-cell tumors or gestational choriocarcinoma. The basic combination consists of POMB (vincristine, methotrexate, bleomycin, and high-dose cis-platinum) and ACE (VP-16, actinomycin D, and cyclophosphamide). Patients receive two courses of POMB, then ACE, then POMB again. Patients with larger volume disease continue with POMB and ACE until biochemical remission is achieved, as indicated by tumor marker levels. Of 112 male patients with malignant germ-cell tumors, some of whom had previous radiotherapy or chemotherapy, and more than 50% of whom had advanced disease, the current survival rate is 87%. The survival rate is 77% for the worst-prognosis patient group. Patients with brain metastases from germ-cell tumors have not required surgery or radiotherapy to achieve a durable complete remission. Among patients who have multiple resistance to drugs such as vinblastine, bleomycin, and cis-platinum, 50% have achieved remission when treated with the EP/OMB schedule (VP-16 and cis-platinum alternated with vincristine, methotrexate, and bleomycin) repeated at short intervals. In 76 drug-resistant patients with gestational choriocarcinoma (medium risk), VP-16 was given intravenously (IV) 100 mg/m2/d for five days as initial therapy, with methotrexate given 11 to 13 days later. Overall response rate including partial response and improvement is 78%. In high-risk gestational choriocarcinoma patients, a weekly schedule of chemotherapy, alternating EMA (VP-16, methotrexate, actinomycin D, and folinic acid) with CO (vincristine and cyclophosphamide), has resulted in an overall survival of 84%; survival in patients who received previous chemotherapy is 73%; and survival in those who did not receive previous chemotherapy, 93%. Mucosal toxicity has not been a major problem. It is recommended that in patients with germ-cell tumors and in medium- and high-risk gestational choriocarcinoma patients, VP-16 be used in initial therapy and not be retained for relapse therapy only.