Cummings School, Tufts University, Foster Hospital for Small Animals, 200 Westboro Rd, N., Grafton, MA, 01536, USA.
Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
BMC Vet Res. 2019 Aug 13;15(1):291. doi: 10.1186/s12917-019-2032-4.
Oclacitinib is an orally bioavailable Janus Kinase (JAK) inhibitor approved for the treatment of canine atopic dermatitis. Aberrant JAK/ Signal Transducer and Activator of Transcription (STAT) signaling within hematologic and solid tumors has been implicated as a driver of tumor growth through effects on the local microenvironment, enhancing angiogenesis, immune suppression, among others. A combination of JAK/STAT inhibition with cytotoxic chemotherapy may therefore result in synergistic anti-cancer activity, however there is concern for enhanced toxicities. The purpose of this study was to evaluate the safety profile of oclacitinib given in combination with either carboplatin or doxorubicin in tumor-bearing dogs.
Oclacitinib was administered at the label dose of 0.4-0.6 mg/kg PO q12h in combination with either carboplatin at 250-300 mg/m or doxorubicin at 30 mg/m IV q21d. Nine dogs were enrolled in this pilot study (n = 4 carboplatin; n = 5 doxorubicin). No unexpected toxicities occurred, and the incidence of adverse events with combination therapy was not increased beyond that expected in dogs treated with single agent chemotherapy. Serious adverse events included one Grade 4 thrombocytopenia and one Grade 4 neutropenia. No objective responses were noted.
Oclacitinib is well tolerated when given in combination with carboplatin or doxorubicin. Future work is needed to explore whether efficacy is enhanced in this setting.
奥卡替尼是一种口服生物可利用的 Janus 激酶（JAK）抑制剂，已获批准用于治疗犬过敏性皮炎。血液系统和实体肿瘤中异常的 JAK/信号转导子和转录激活子（STAT）信号已被认为是通过对局部微环境的影响，增强血管生成、免疫抑制等，驱动肿瘤生长的因素之一。JAK/STAT 抑制与细胞毒性化疗联合使用可能因此产生协同抗癌活性，但人们担心会增强毒性。本研究的目的是评估在荷瘤犬中奥卡替尼与卡铂或阿霉素联合使用的安全性概况。
奥卡替尼按标签剂量 0.4-0.6mg/kg PO q12h 与卡铂 250-300mg/m 或阿霉素 30mg/m IV q21d 联合使用。本试验性研究纳入了 9 只犬（n=4 只卡铂；n=5 只阿霉素）。未发生意外毒性，联合治疗的不良事件发生率并未超过单药化疗治疗犬的预期发生率。严重不良事件包括 1 例 4 级血小板减少症和 1 例 4 级中性粒细胞减少症。未观察到客观缓解。
奥卡替尼与卡铂或阿霉素联合使用时耐受性良好。需要进一步研究以探索在这种情况下是否增强了疗效。
