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苯丁酸氮芥与托西拉尼联合治疗犬不同实体瘤的回顾性安全性评估

Retrospective Safety Evaluation of Combined Chlorambucil and Toceranib for the Treatment of Different Solid Tumours in Dogs.

作者信息

Lai Yuk-Yin, Horta Rodrigo Dos Santos, Valenti Paola, Giuliano Antonio

机构信息

Jockey Club College of Veterinary Medicine, City University of Hong Kong, Kowloon, Hong Kong, China.

Department of Veterinary Medicine and Surgery, Veterinary School, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil.

出版信息

Animals (Basel). 2024 Nov 26;14(23):3420. doi: 10.3390/ani14233420.

Abstract

Chlorambucil is used in veterinary medicine for various cancers, while Toceranib, which was licenced for treating canine mast cell tumours, is now used against other solid tumours. Both drugs are generally safe, but their combined use has not been studied. This study aimed to investigate retrospectively the safety profile of the Chlorambucil-Toceranib combination against canine solid tumours. Thirty-eight dogs received this combination. Chlorambucil was administered at a median dose intensity of 15.1 mg/m per week, while Toceranib was given at the median dosage of 2.5 mg/kg on a Monday-Wednesday-Friday schedule. Dosages were individually adjusted according to commercially available tablet formulation, co-morbidities, and adverse events (AEs). The resulting clinical benefit rate (CBR) and overall response rate (ORR) were 55.3% and 10.5%, respectively. The median progressive free survival (PFS) and median survival time (MST) were 45.5 (12-537) days and 259 (42-1178) days, respectively. Gastrointestinal AEs occurred in 39.5% of cases ( = 15), 15.8% ( = 6) experienced UPC elevation, while hematological and biochemistry AEs affected 13.2% ( = 5) each. Most of these AEs were grades 1-2 (G1-2). None of the dogs interrupted treatment due to AEs, and the combination appeared safe. Larger prospective clinical trials are required to confirm our findings and investigate its efficacy across various cancers.

摘要

苯丁酸氮芥在兽医学中用于治疗各种癌症,而曾被批准用于治疗犬肥大细胞瘤的托西替尼,现也用于治疗其他实体瘤。这两种药物一般来说都是安全的,但它们的联合使用尚未得到研究。本研究旨在回顾性调查苯丁酸氮芥 - 托西替尼联合用药治疗犬实体瘤的安全性。38只犬接受了这种联合治疗。苯丁酸氮芥的给药中位剂量强度为每周15.1毫克/平方米,而托西替尼按周一至周三至周五的给药方案,以2.5毫克/千克的中位剂量给药。剂量根据市售片剂剂型、合并症和不良事件(AE)进行个体化调整。由此得出的临床获益率(CBR)和总缓解率(ORR)分别为55.3%和10.5%。中位无进展生存期(PFS)和中位生存期(MST)分别为45.5(12 - 537)天和259(42 - 1178)天。39.5%(n = 15)的病例出现胃肠道不良事件,15.8%(n = 6)的犬出现碱性磷酸酶升高,而血液学和生化不良事件各影响13.2%(n = 5)的犬。这些不良事件大多为1 - 2级(G1 - 2)。没有一只犬因不良事件中断治疗,联合用药似乎是安全的。需要更大规模的前瞻性临床试验来证实我们的发现,并研究其对各种癌症的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ba2/11640119/da9fd514103a/animals-14-03420-g001.jpg

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