Gigante M, Sorio R, Colussi A M, Sandrin A, De Appollonia L, Galligioni E, Freschi A, Talamini R, Toffoli G, Boiocchi M
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
Anticancer Drugs. 1995 Jun;6(3):479-82. doi: 10.1097/00001813-199506000-00019.
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.
五名转移性肾细胞癌（RCC）患者进入了本研究。这些患者接受了两个疗程的替尼泊苷（VM26）（200mg/m²/24小时静脉注射），之后未观察到客观缓解：三名患者病情稳定（SD），两名患者病情进展。然后加入环孢素（CsA）（5mg/kg/2小时，随后30mg/kg/48小时静脉注射）（VM26/CsA），并至少再给予两个疗程。分析了药代动力学和药效学参数。CsA使五名患者中的四名患者的VM26曲线下面积（AUC）增加；平均而言，VM26配对AUC的变化为41%。与VM26治疗后相比，VM26/CsA治疗后的最低点粒细胞计数更低（平均650/mm³，范围为<100至1800/mm³）（VM26治疗后平均1260/mm³，范围为200至2100/mm³）（p<0.01）。与VM26相比，VM26/CsA治疗后血清胆红素浓度升高（p<0.05）。最后，经过两个疗程的VM26/CsA治疗后，四名患者病情稳定，一名患者有轻微缓解。总之，正在进行的初步研究表明，CsA会影响VM26的药代动力学和药效学。
