title: Effect of cyclosporine on teniposide pharmacokinetics and pharmacodynamics in patients with renal cell cancer.
abstract: 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.
authors.affiliation: Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gigante
authors.forename: R
authors.initials: R
authors.lastname: Sorio
authors.forename: A M
authors.initials: AM
authors.lastname: Colussi
authors.forename: A
authors.initials: A
authors.lastname: Sandrin
authors.forename: L
authors.initials: L
authors.lastname: De Appollonia
authors.forename: E
authors.initials: E
authors.lastname: Galligioni
authors.forename: A
authors.initials: A
authors.lastname: Freschi
authors.forename: R
authors.initials: R
authors.lastname: Talamini
authors.forename: G
authors.initials: G
authors.lastname: Toffoli
authors.forename: M
authors.initials: M
authors.lastname: Boiocchi
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002452:Cell Count / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013713:Teniposide / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D016572:Cyclosporine; D013713:Teniposide; D001663:Bilirubin