New prospects for the treatment of germ-cell tumours

Germ-cell tumours are rare tumours of testicular, ovarian and extra-gonadal origins. Most are curable by cisplatin-based chemotherapy regimens and surgery. Treatment strategy is based on risk factor assessment. The standard cytotoxic drugs used for the treatment of this disease are: etoposide, cisplatin, bleomycin and ifosfamide. More than 80% of patients are cured by standard treatment. There is a dose-response relationship for cisplatin, up to standard 33 mg/m2/week/dose-intensity. However, further dose escalation has failed to demonstrate an increased response. Carboplatin has been shown to be less active than cisplatin. Activity has been demonstrated with nitrogen mustard, actinomycin, mithramycin, vinblastine, methotrexate and recently with paclitaxel and gemcitabine. Activity is questionable with carboplatin, oxaliplatin, lobaplatin, mitomycin and anthracyclins. No activity has been reported with vindesine, vinorelbine, mitoxantrone, AMSA and topotecan. New treatment strategies are developed in poor-risk group patients and in patients who fail to achieve complete remission status or whom experience recurrent disease. Intensification of chemotherapy is one of the tested strategies. Consolidation high-dose chemotherapy with haematopoietic stem-cell support is under evaluation. Until now, no trial has proven its superiority over standard chemotherapy regimens. Other studies concern the role of repeated cycles of high-dose chemotherapy with haematological support. Innovative strategies consist of introducing new drugs or new schedules: paclitaxel in combination with either ifosfamide and cisplatin or epirubicin, short, recycled chemotherapy regimens, use of cisplatin non-cross-resistant drugs and different time infusion administration of drugs. The aim of these studies is to decrease the residual proportion of treatment failures in this highly curable disease, which constitutes a good model for clinical research in cancer chemotherapy.