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.