Lindkær-Jensen Steen, Larsen Stig, Habib-Lindkær-Jensen Nina, Fagertun Hans E
Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK.
Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway.
Drug Des Devel Ther. 2015 Mar 13;9:1481-90. doi: 10.2147/DDDT.S80451. eCollection 2015.
A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.
The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose-response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.
Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K(+), Ca(2+), and PO4 (3-) was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg(2+), prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values.
Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In contrast, BP-C1 corrected abnormalities. No hematological and biochemical toxicity was observed.
一种苯多羧酸与顺二氯二氨合铂（II）的复合物，即BP-C1，目前正用于转移性乳腺癌的临床试验。BP-C1可控制肿瘤生长，副作用轻微，能改善生活质量。
数据包括在两项对照临床试验中对47例患者进行每日肌肉注射BP-C1共32天的前瞻性收集的实验室结果。研究I作为一项开放、非随机的I期剂量反应多中心研究，采用三级、患者间反应面途径设计。第二项研究是一项随机、双盲、安慰剂对照的多中心研究，采用分层半交叉设计。
在BP-C1治疗期间，血红蛋白（Hb）和血细胞比容（Hct）显著升高（P<0.01），而红细胞（RBC）计数虽有增加但不显著。Hb、RBC、Hct和白细胞（WBC）升高最明显的是贫血患者（P≤0.01）。总体数据中白细胞计数和中性粒细胞显著增加（P=0.01）。基线水平最低的患者中白细胞和中性粒细胞（P<0.01）、嗜酸性粒细胞（P=0.05）和单核细胞（P<0.01）显著且明显增加。此外，低水平的血小板显著增加。除了基线水平低的亚组中白蛋白水平显著升高（P=0.04）外，未检测到肝参数、淀粉酶、葡萄糖、肌酐或白蛋白有变化。基线水平低的患者中钾（K+）、钙（Ca2+）和磷酸根（PO4 3-）升高最明显（P≤0.02）。镁（Mg2+）、凝血酶原时间（PT）、凝血因子II、VII、X（KFNT）和C反应蛋白（CRP）也检测到类似模式，在数值最低的组中显著升高（P≤0.05）。
我们的研究结果支持BP-C1用于癌症患者的安全性。BP-C1不会诱发贫血、感染、出血、肝功能不全或电解质失衡。相反，BP-C1纠正了异常情况。未观察到血液学和生化毒性。
