Clinical outcome of dogs diagnosed with canine inflammatory mammary cancer treated with metronomic cyclophosphamide, a cyclooxygenase-2 inhibitor and toceranib phosphate
Clinical outcome of dogs diagnosed with canine inflammatory mammary cancer treated with metronomic cyclophosphamide, a cyclooxygenase-2 inhibitor and toceranib phosphate
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DOI：
10.1111/vco.12760
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发表时间：
2021-08-19
影响因子：
2.1
通讯作者：
Perez-Alenza, Maria Dolores
中科院分区：
文献类型：
--
作者：
Alonso-Miguel, Daniel;Valdivia, Guillermo;Perez-Alenza, Maria Dolores
犬炎性乳腺癌（IMC）是一种高度恶性、侵袭性和治疗挑战，因为有效的药物治疗仍然不可用。本回顾性研究比较了口服环氧化酶-2 （COX-2）抑制剂联合磷酸托ceranib和口服环磷酰胺（多药治疗[MT]）与单独COX-2抑制剂治疗（单药治疗[ST]）对继发性IMC犬的疗效。评估临床反应、不良事件、总生存时间（OST）、无病生存时间（DFS）和进展时间（TTP）。纳入16例患者，其中8例接受MT， 8例接受st。接受MT患者的中位OST （96.0 vs. 37.5天，p = 0.046）和术后IMC患者的中位OST显著高于非手术IMC患者（86.5 vs. 41.5天，p = 0.038）。此外，接受MT治疗的患者中位TTP显著升高（p = 0.010）。在非手术IMC患者中，100% （n = 3）接受MT的患者和33% （n = 1）接受ST的患者达到了临床获益（CB）；MT病例的反应持续时间明显更长（p = 0.026）。治疗第30天无疾病进展与较长的OST、DFS和TTP显著相关（p = 0.018、p = 0.002和p < 0.001）。MT组患者的不良事件发生率高于ST组（p = 0.026）。MT方案主要产生轻度至中度毒性，通过支持治疗解决；因此，大多数患者对联合用药有足够的耐受性。COX-2抑制剂toceranib联合口服环磷酰胺可能是一种具有潜在疗效的治疗IMC犬的方案。
Canine inflammatory mammary cancer (IMC) is highly malignant, invasive and a therapeutic challenge, because effective medical treatment is still unavailable. This retrospective study compares the efficacy of an oral cyclooxygenase-2 (COX-2) inhibitor combined with toceranib phosphate and oral cyclophosphamide (multi-drug therapy [MT]) with COX-2 inhibitor therapy alone (single-drug therapy [ST]) in dogs diagnosed with secondary IMC. Clinical response, adverse events, overall survival time (OST), disease-free survival (DFS) and time to progression (TTP) were evaluated. Sixteen patients were included, eight received MT and eight receiving ST. Median OST was significantly higher in patients receiving MT (96.0 vs. 37.5 days; p = .046) and in patients with post-surgical rather than non-surgical IMC (86.5 vs. 41.5 days; p = .038). Additionally, median TTP was significantly higher in patients treated with MT (p = .010). In patients with non-surgical IMC, the clinical benefit (CB) was reached in 100% (n = 3) of patients receiving MT and in 33% (n = 1) of those receiving ST; the response duration was significantly longer in MT cases (p = .026). The absence of disease progression at day 30 of treatment was significantly associated with longer OST, DFS and TTP (p = .018, p = .002 and p < .001, respectively). Adverse events occurred more frequently in patients treated with MT compared with ST (p = .026). The MT protocol produced primarily mild to moderate toxicities, which were resolved with supportive care; therefore, the combination of drugs was adequately tolerated by most of the patients. The combination of toceranib, a COX-2 inhibitor and oral cyclophosphamide may be a protocol with potential therapeutic efficacy for dogs with IMC.