Pan X, Tsimbas K, Kurzman I D, Vail D M
School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
Vet Comp Oncol. 2016 Jun;14(2):202-9. doi: 10.1111/vco.12091. Epub 2014 Apr 16.
While maintaining a standard toceranib dosage [2.75 mg kg(-1) , PO, every other day (EOD)], three dose-escalating CCNU cohorts up to and including 60 mg m(-2) , PO, q3wk, were completed. The dose-limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m(-2) , q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg(-1) , EOD) and pulse dose CCNU (50 mg m(-2) , q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.
在维持标准的托西拉尼剂量[2.75mg/kg，口服，隔日一次（EOD）]的同时，完成了三个剂量递增的洛莫司汀队列研究，剂量最高达60mg/m²，口服，每3周一次（q3wk）。该联合用药的剂量限制性毒性（DLT）为中性粒细胞减少，当与持续使用的托西拉尼联用时，洛莫司汀的最大耐受剂量（MTD）被确定为50mg/m²，每3周一次。虽然活性不是I期试验的主要目标，但我们观察到1例完全缓解（淋巴瘤）和4例部分缓解（淋巴瘤、肉瘤、未分化癌和前列腺癌），2只犬病情稳定>6周[胃腺癌和转移性多叶性骨软骨肉瘤（MLO）]，客观缓解率为38.4%，生物学缓解率为53.8%。同时持续使用托西拉尼（2.75mg/kg，EOD）和脉冲剂量洛莫司汀（50mg/m²，q3wk）耐受性良好。II期有效性试验和III期前瞻性随机试验应进一步探究该联合用药的潜在活性。
