Risk-Adapted Chemotherapy of Germ Cell Tumors with Carboplatin, Etoposide and Bleomycin for Low-Risk and Cisplatin, Etoposide and Ifosfamide for High-Risk Patients

Abstract

The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, βHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and βHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 1–3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB90). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m2 continuous infusion on days 1–4 together with mesna 1,200 mg/m2 days 1–5, cisplatin 20 mg/m2 i.v. days 1–5 and etoposide 100 mg/m2 i.v. days 1–5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB90 achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB90, 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80–98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB90 were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81–99%). We thus confirm that CEB90 is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.