Edta Clearance in Monitoring Cisplatin Dose Escalation in Patients with Bulky Metastatic Germ Cell Tumors of the Testis

Abstract

A fast cisplatin clearance may reduce exposure time of tumor cells to the drug, and thus impair the expected effects of dose escalation. This hypothesis was tested in 23 patients with bulky metastatic germ cell tumors of the testis, treated with etoposide, bleomycin and high-dose cisplatin (60 mg/m²/24 h×4). The daily dose was retrospectively calculated in mg/1 EDTA clearance/24 h. A daily dose of 60 mg/m² of cisplatin in a person with a body surface of 1.7 m² and EDTA clearance of 100 ml/min was equivalent to 0.69 mg cisplatin/l EDTA clearance/24 h. In the whole group, 10 patients had complete remission (CR), 10 partial response (PR) and 3 progressive disease (PD). The mean daily cisplatin dose (×) in the whole group was 0.86 mg/1 EDTA clearance/24 h (range 0.35–2.00). For patients with CR, × × SD was 1.00±0.46, for those with PR 0.80±0.44, and for those with PD only 0.61±0.07. A cisplatin dose over 0.86 mg/1 EDTA clearance/24 h × 4 was obtained in 6/10 patients with CR versus 2/13 patients with PR + PD. Patients with PD received a significantly lower cisplatin dose than the whole group (0.61 versus 0.86 mg cisplatin/l EDTA clearance/24 h × 4.) The difference between the average toxicity grade after cisplatin dose over and below 0.69 mg/l EDTA clearance/24 h × 4 was significant only for leukocytes (WHO grade 2.17 versus 1.36). Thus, the effective escalated dose of cisplatin should preferably be calculated not per m² body surface but per 1 liter EDTA clearance. The ‘ideal’ escalated dose might be about 0.86–1.0 mg cisplatin/l EDTA clearance 24 h × 4.