While current lymphoma therapies induce remission in most dogs, drug‐resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9‐(2‐phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty‐three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T‐cell immunophenotype and corticosteroid pre‐treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG‐CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.

中文翻译：

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Rabacfosadine 治疗幼犬中间大细胞淋巴瘤：三项前瞻性临床试验的疗效和不良事件概况。

虽然目前的淋巴瘤疗法在大多数狗中诱导缓解，但耐药性复发很常见，因此需要新的药物。Rabacfosadine (RAB) 是无环核苷酸膦酸酯 9-(2-膦酰甲氧基乙基) 鸟嘌呤 (PMEG) 的双前药，与 PMEG 相比，它优先靶向淋巴瘤细胞，其全身毒性降低。以前每 21 天评估一次 RAB 的研究表明，对初治和复发受试者均有效；然而，在先前未经治疗的患有中至大细胞淋巴瘤的犬中，没有报道将 RAB 作为单一药物进行的大型研究。本研究的目的是评估 RAB 对先前未治疗（不包括皮质类固醇）淋巴瘤的狗的安全性和有效性。63 只狗每 21 天接受多达 5 次 RAB 治疗（16 只 0.82 mg/kg，47 只 1. 0 mg/kg) 作为 30 分钟静脉输注，有 (n = 23) 或没有 (n = 40) 并发皮质类固醇。通过兽医合作肿瘤学组 (VCOG) 标准每 21 天进行一次反应评估和不良事件 (Ae) 评估。总体反应率为 87%（52% CR，35% PR）。总体中位无进展时间间隔为 122 天（CR 为 199，PR 为 89，所有应答者为 153 天）。在多变量分析中，T 细胞免疫表型和皮质类固醇预处理可预测较差的结果。AE 最常见的是胃肠道来源（缺氧/腹泻），通常通过支持治疗和/或剂量调整来解决。三只狗经历了 VCOG-CTCAE 5 级迟发性肺纤维化。综上所述，