Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m², etoposide 120–150 mg/m² and ifosfamide 1.2 g/m² for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died ofClostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/l and a thrombocyte nadir of 47000/l. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m², etoposide 150 mg/m² and ifosfamide 1.6 g/m² five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 g/kg on days 6–15. Acute toxicity was severe with a white blood cell nadir of 300/l and thrombocyte nadir of 11 000/l. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure andAspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m², etoposide 200 mg/m² and ifosfamide 1.6 g/m² for 5 days and GMCSF 10 g kg^–1 day^–1 on days 6–15 s.c.Presented at the Satellite Symposium Ifosfamide in Tumor Therapy: Questions for the Nineties; 15th International Cancer Congress, Hamburg, August 16–22, 1990