Management of intermediate-prognosis germ-cell cancer: Results of a phase I/II study of Taxol-BEP

The standard chemotherapy regimen in metastatic germ-cell cancer is bleomyc in, etoposide and cisplatin (BEP). Chemotherapy studies testing cisplatin d osage and the substitution of ifosfamide for bleomycin have not shown this to be superior to BEP. Paclitaxel (Taxol) has demonstrated promising activi ty as a second-line treatment in patients with relapsing or cisplatin-refra ctory germ-cell cancer. Hence, the potential of incorporating paclitaxel in first-line chemotherapy should be investigated. We assessed the feasibilit y of the addition of paclitaxel to BEP (T-BEP) in a phase I/II study in pat ients with intermediate- or poor-prognosis germ-cell cancer or with carcino ma of unknown primary (CUP). Paclitaxel was investigated at dose levels of 75, 125, 175 and 200 mg/m(2) given as a 3 hr infusion on day I, before the start of BEP. BEP comprised etoposide at a dose of either 120 mg/m(2) on da ys 1, 3 and 5 or 100 mg/m(2) on days 1-5. To deliver the highest possible d ose of paclitaxel into BEP, all patients received filgrastim (G-CSF). Thirt y patients were entered, 14 of whom had intermediate-(n = 7) or poor-(n = 7 ) prognosis germ-cell cancer. Paclitaxel up to 200 mg/m(2) and BEP at 360 m g/m(2) was well tolerated. There was minimal neurosensory and no neuromotor toxicity with the use of 4 T-BEP cycles. More pronounced myelotoxicity and diarrhea at the higher dose level of etoposide resulted in a recommended d ose revel for multicenter phase II/III testing of paclitaxel 175 mg/m(2) an d BEP 500 mg/m(2). Of the 13 evaluable patients with intermediate- or poor- prognosis germ-cell cancer, all achieved complete response. With a median f ollow-up of 18 months, none of these patients has relapsed. We conclude tha t T-BEP is a well-tolerated induction regimen that should be further tested for its therapeutic potential. A randomized phase II/III study of T-BEP vs . BEP has been started as an EORTC trial in patients with intermediate-prog nosis disease. (C) 1999 Wiley-Liss, Inc.