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 bleomycin, etoposide and cisplatin (BEP). Chemotherapy studies testing cisplatin dosage and the substitution of ifosfamide for bleomycin have not shown this to be superior to BEP. Paclitaxel (Taxol) has demonstrated promising activity as a second-line treatment in patients with relapsing or cisplatin-refractory germ-cell cancer. Hence, the potential of incorporating paclitaxel in first-line chemotherapy should be investigated. We assessed the feasibility of the addition of paclitaxel to BEP (T-BEP) in a phase I/II study in patients with intermediate- or poor-prognosis germ-cell cancer or with carcinoma of unknown primary (CUP). Paclitaxel was investigated at dose levels of 75, 125, 175 and 200 mg/m2 given as a 3 hr infusion on day 1, before the start of BEP. BEP comprised etoposide at a dose of either 120 mg/m2 on days 1, 3 and 5 or 100 mg/m2 on days 1-5. To deliver the highest possible dose of paclitaxel into BEP, all patients received filgrastim (G-CSF). Thirty patients were entered, 14 of whom had intermediate- (n = 7) or poor- (n = 7) prognosis germ-cell cancer. Paclitaxel up to 200 mg/m2 and BEP at 360 mg/m2 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 dose level for multicenter phase II/III testing of paclitaxel 175 mg/m2 and BEP 500 mg/m2. Of the 13 evaluable patients with intermediate- or poor-prognosis germ-cell cancer, all achieved complete response. With a median follow-up of 18 months, none of these patients has relapsed. We conclude that 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-prognosis disease.