Gietema J A, Veldhuis G J, Guchelaar H J, Willemse P H, Uges D R, Cats A, Boonstra H, van der Graaf W T, Sleijfer D T, de Vries E G
Department of Medical Oncology, University Hospital Groningen, The Netherlands.
Br J Cancer. 1995 Jun;71(6):1302-7. doi: 10.1038/bjc.1995.252.
In phase I studies, lobaplatin showed activity in ovarian cancer patients pretreated with platinum. A phase II trial with lobaplatin was performed in patients with refractory or relapsed ovarian cancer to define activity and pharmacokinetics. Twenty-two patients were treated with lobaplatin administered as an intravenous bolus every 4 weeks. Dependent on creatinine clearance (CRCL) patients received 30 or 50 mg m-2 lobaplatin as the starting dose. Twenty-two patients received 78 courses (median 3, range 1-6). In eight patients total platinum (TPt) in plasma and urine, free platinum (FPt) in plasma ultrafiltrate (both measured by atomic absorption spectrometry) and lobaplatin in plasma ultrafiltrate measured (by high-performance liquid chromatography) were measured. Toxicity was confined to mild nausea and vomiting, mild leucocytopenia (WHO grade 3 in 18% of the courses), and renal function-related thrombocytopenia (WHO grade 3/4 in 53% of the courses). A correlation was found between CRCL and reduction in platelet count (r = -0.77; P < 0.01). No renal toxicity was encountered. Five of 21 evaluable patients (24%) achieved a response (four complete remissions and one partial remission). Remissions occurred mainly in patients who relapsed more than 6 months after primary treatment. The median survival from start of lobaplatin treatment was 8 months. The mean areas under the curve (AUCs) were 4.2 +/- 0.5, 3.0 +/- 0.6, and 3.2 +/- 1.1 h mgl-1 for TPt, FPt and lobaplatin respectively. The free platinum fraction (FPt/TPt) was initially very high, indicating low protein binding. FPt was essentially present as intact lobaplatin. Four hours after infusion 54 +/- 5% and 24 h after infusion 74 +/- 3% of the lobaplatin dose was excreted in the urine. In conclusion, lobaplatin is a platinum compound with anti-tumour activity in patients with relapsed ovarian cancer, especially in those who have platinum-sensitive tumours. The main toxicity of lobaplatin is thrombocytopenia and its dose should be corrected according to renal function.
在I期研究中，洛铂在接受过铂类预处理的卵巢癌患者中显示出活性。对难治性或复发性卵巢癌患者进行了一项洛铂的II期试验，以确定其活性和药代动力学。22例患者接受洛铂治疗，每4周静脉推注一次。根据肌酐清除率（CRCL），患者接受30或50mg/m²的洛铂作为起始剂量。22例患者共接受了78个疗程（中位数3个，范围1 - 6个）。对8例患者测定了血浆和尿液中的总铂（TPt）、血浆超滤液中的游离铂（FPt，均通过原子吸收光谱法测定）以及血浆超滤液中的洛铂（通过高效液相色谱法测定）。毒性仅限于轻度恶心和呕吐、轻度白细胞减少（18%的疗程为WHO 3级）以及与肾功能相关的血小板减少（53%的疗程为WHO 3/4级）。发现CRCL与血小板计数降低之间存在相关性（r = -0.77；P < 0.01）。未出现肾毒性。21例可评估患者中有5例（24%）获得缓解（4例完全缓解和1例部分缓解）。缓解主要发生在初次治疗后复发超过6个月的患者中。从开始洛铂治疗起的中位生存期为8个月。TPt、FPt和洛铂的平均曲线下面积（AUC）分别为4.2±0.5、3.0±0.6和3.2±1.1h mg⁻¹。游离铂分数（FPt/TPt）最初非常高，表明蛋白结合率低。FPt基本上以完整的洛铂形式存在。输注后4小时，54±5%的洛铂剂量经尿液排出，输注后24小时，74±3%的洛铂剂量经尿液排出。总之，洛铂是一种对复发性卵巢癌患者具有抗肿瘤活性的铂类化合物，尤其是对铂敏感肿瘤患者。洛铂的主要毒性是血小板减少，其剂量应根据肾功能进行调整。
