Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study
Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study
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DOI：
10.1111/j.1476-5829.2011.00265.x
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发表时间：
2012-09-01
影响因子：
2.1
通讯作者：
Vail, D. M.
中科院分区：
文献类型：
--
作者：
Chon, E.;McCartan, L.;Vail, D. M.
Toceranib磷酸盐和吡罗昔康已分别显示出抗肿瘤活性。此外，非甾体类抗炎治疗通常在老年荷癌犬中用于骨关节炎合并症的管理。由于给定个体可能需要同时使用，并且每种药物的不良事件（AE）特征可能重叠（胃肠道），因此在荷瘤（非肥大细胞）犬中进行了I期试验，以使用标准3 + 3队列设计确定联合用药的安全性。完成了5个剂量递增队列，直至并包括批准的toceranib标签剂量和吡罗昔康标准剂量，未观察到需要关闭队列的剂量限制性AE频率。因此，两种药物的标准剂量组合（toceranib，3.25 mg kg-1，每隔一天;吡罗昔康，0.3 mg kg-1每日）通常是安全的。观察到几种抗肿瘤反应。与toceranib单药治疗一样，由于胃肠道事件，有时可能需要标签指示的治疗假期和剂量降低（例如2.52.75 mg kg-1）。
Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg-1, every other day; piroxicam, 0.3 mg kg-1 daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.52.75 mg kg-1) may occasionally be required owing to gastrointestinal events.