Effect of cyclosporine on teniposide pharmacokinetics and pharmacodynamics in patients with renal cell cancer

Five patients with metastatic renal cell cancer (RCC) entered this study. The patients received two courses of teniposide (VM26) (200 mg/m²/24 h i.v.) after which no objective response was observed: three patients had stable disease (SD) and two had progressive disease. Cyclosporine (CsA) (5 mg/kg/2 h followed by 30 mg/kg/48 h i.v.) was then added (VM26/Csa) and at least another two courses were administered. Pharmacokinetic and pharmacodynamic parameters were analyzed. CsA increased the area under curve (AUC) of VM26 in four out of five patients; on average, the variation in the paired AUC of VM26 was 41%. Nadir granulocyte count was lower (average 650/mm³, ranging from <100 to 1800/mm³) after VM26/CsA than after VM26 (average 1260/mm³, ranging from 200 to 2100/mm³) (p <0.01). Bilirubin concentration in the serum was increased after VM26/CsA compared with VM26 (p <0.05). Finally, after two courses of VM26/CsA, four patients had stable disease and one patient had a minor response. In conclusion, the ongoing pilot study indicates that CsA affects both the pharmacokinetics and the pharmacodynamics of VM26.