比較敏伯斯登與伊馬替尼治療犬高風險皮膚肥大細胞瘤之治療效果

Abstract

肥大細胞瘤是犬隻最常見的皮膚腫瘤，在無法進行局部控制的情況下會使用化學治療以及標靶治療等全身性治療。敏伯斯登為常用於肥大細胞瘤的第一線化療藥物，除了單用之外也會搭配其他化療藥物使用，例如環磷醯胺。伊馬替尼是一個酪氨酸激酶抑制劑，近期被發現可透過抑制失調的 KIT 蛋白進而抑制肥大細胞瘤。然而個別病患應選擇化療還是標靶治療目前並沒有定論，因此本篇研究的目的為比較在患有高轉移風險皮膚型肥大細胞瘤的犬隻使用以敏伯斯登為基礎的化療和伊馬替尼的效果與毒性，並分析與無惡化存活期相關的預後因子。 本研究回溯性納入西元 2011 至 2019 年間，於國立臺灣大學生物資源暨農學院附設動物醫院動物癌症治療中心以組織病理學或細胞學確診且無法切除之高轉移風險皮膚型肥大細胞瘤，並使用以敏伯斯登為基礎的化療或伊馬替尼治療的犬隻，分為敏伯斯登組(n = 21)以及伊馬替尼組(n = 20)進行比較。兩組的客觀反應率沒有顯著差異(敏伯斯登組為 42.9%，伊馬替尼組為 35.0%，P = 0.606)，然而敏伯斯登組的臨床受益率(100.0%)顯著高於伊馬替尼組(80.0%，P = 0.048)。兩組的中位無惡化存活期沒有顯著差異(敏伯斯登組為 83 天，伊馬替尼組為 51 天，P = 0.885)。敏伯斯登組的總體副作用發生率(71.4%)顯著高於伊馬替尼組 (35.0%，P = 0.019)，而在個別比較時也有達到顯著差異的副作用種類為嗜中性球低下(P = 0.048)以及精神不振(P = 0.021)。預後因子的部分，年紀小於 11 歲的 犬隻有顯著較長的中位無惡化存活期(P = 0.033)，臨床分期第二期的犬隻也較第四期的犬隻有顯著更長的中位無惡化存活期(P = 0.049)。 總結來說，使用以敏伯斯登為基礎的化療和伊馬替尼的治療效果相當，但敏伯斯登組有較顯著的副作用。因此，在預期容易出現副作用並注重生活品質維持的病 患可以建議使用伊馬替尼。年齡與臨床分期為影響無惡化存活期的預後因子。

Mast cell tumor (MCT) is the most common canine cutaneous neoplasm. In cases that complete local control is impossible; often, systemic treatments are indicated, such as chemotherapy and tyrosine kinase inhibitor (TKI). Vinblastine (VBL) is a first-line chemotherapeutic agent often used alone or with other chemotherapeutic agents, such as cyclophosphamide (CTX). Imatinib is a TKI that has been recently shown to induce remission of MCT by inhibiting dysregulated KIT protein expression. The choice between chemotherapy and TKI for an individual patient remains equivocal. Therefore, the purpose of this study was to compare the efficacy and safety of VBL-based chemotherapy and imatinib in high-risk canine cutaneous MCT. The potential prognostic factors for the progression-free interval (PFI) were also investigated. Dogs diagnosed with measurable high-risk cutaneous MCT by histopathology or cytology treated with VBL-based chemotherapy or imatinib alone at National Taiwan University Veterinary Hospital Animal Cancer Treatment Center from 2011 to 2019 were retrospectively enrolled and divided into VBL group (n = 21) or imatinib group (n = 20). The objective response rate (ORR) was similar between the VBL group and the imatinib group (42.9% versus 35.0%, P = 0.606). However, the clinical benefit rate (CBR) was significantly higher for VBL group (100.0% versus 80.0%, P = 0.048). The median PFI was 83 days for the VBL group and 51 days for the imatinib group (P = 0.885). The incidence of side effects was significantly higher for VBL group (71.4% versus 35.0%, P = 0.019), especially for neutropenia and lethargy (P = 0.048 and P = 0.021, respectively). As for prognostic factors, median PFI was significantly longer for dogs younger than 11 years old, and also higher for dogs classified as stage 2 compared to stage 4 upon multivariate analysis (P = 0.033 and P = 0.049, respectively). In conclusion, the efficacy was similar between dogs treated with VBL-based chemotherapy and imatinib, but the toxicity was more prominent in the VBL group. Therefore, imatinib may be advocated for patients that are expected to be more susceptible to adverse events and considering the quality of life. Age and clinical stage were prognostic factors for PFI in this study.