Experience with dose and schedule variations in germ cell tumors

The majority of patients with metastatic germ cell tumors can be cured with currently available poly-chemotherapy. Based on presenting criteria three prognostic groups can be discerned. In patients with a good prognosis (> 90% probability of 5-year survival) attempts have been made to diminish the dose of the active compounds in the BEP regimen. The omission of bleomycin cannot be recommended on presently available data; and a total dose of at least 240 mg seems appropriate. Platinum at a dose intensity below 75 mg/m2/3 weeks compromised efficacy and the recommended dose is 100 mg/m2. A true comparison between the two most frequently used etoposide doses has not been performed. Based on the available literature etoposide should be given in doses of at least 360 mg/m2/cycle when four courses are given and 500 mg/m2/cycle when three courses are given. For intermediate and high-risk patients alternating, accelerated and high-dose chemotherapy can be considered. None of the alternating and accelerated regimens has a proven advantage in randomized trials and they remain investigational. The addition of hematopoietic growth factors permits a higher dose intensity of BEP/EP and BOP/VIP; although to date there is no proven impact on outcome. The application of high-dose chemotherapy for one to four courses is feasible with the support of both hematopoietic growth factors and autologous bone marrow or peripheral stem cells. In true chemotherapy-resistant disease the value of this approach seems limited. Its role in patients with a first relapse should be further explored. The approach of high-dose chemotherapy in first line for patients with poor prognostic features should preferentially be investigated in a randomized fashion, but this will require extensive international collaboration in view of the low incidence and the expected advantage of the approach.