Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study

被引:29
作者
Chon, E. [1 ]
McCartan, L. [1 ]
Kubicek, L. N. [1 ]
Vail, D. M. [1 ,2 ]
机构
[1] Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53706 USA
[2] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA
关键词
chemotherapy; non-steroidal anti-inflammatory drugs; oncology; tumour biology; tyrosine kinase; ENDOTHELIAL GROWTH-FACTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TYROSINE KINASE INHIBITOR; CYCLOOXYGENASE-2; EXPRESSION; IMMUNOHISTOCHEMICAL EXPRESSION; RHEUMATOID-ARTHRITIS; RECEPTORS FLT-1; URINARY-BLADDER; CLINICAL-TRIALS; DOUBLE-BLIND;
D O I
10.1111/j.1476-5829.2011.00265.x
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
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.
引用
收藏
页码:184 / 193
页数:10
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