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標題: | 比較使用必諾賓與艾黴素治療貓乳癌之療效與毒性 Comparison of Efficacy and Toxicity of Vinorelbine and Doxorubicin in Feline Mammary Carcinoma |
作者: | Yu-Ting Tung 董育廷 |
指導教授: | 李繼忠 |
關鍵字: | 貓乳癌,必諾賓,艾黴素, Feline mammary carcinoma,vinorelbine,doxorubicin, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 乳癌為貓癌症中第三常見的惡性腫瘤,若罹患乳癌的貓伴隨有高惡性程度腫瘤、腫瘤直徑超過三公分、腫瘤已侵犯淋巴管、血管、淋巴結或遠端轉移,單純的手術切除往往無法達到有效的腫瘤控制,而需要全身性的化學治療來輔助治療的效果,艾黴素為現今最常使用於乳癌的化療藥物之一,然而目前尚缺乏前瞻性且隨機分組的研究來證實艾黴素能夠有效增長存活時間,此外許多文獻都發現以艾黴素治療貓乳癌常伴隨有消化道毒性與累積性的腎臟毒性。必諾賓為一種半合成的長春花生物鹼類化療藥,此藥也被用在治療人類乳房癌中,且消化道毒性大多輕微。因此本研究的目的是要比較必諾賓與艾黴素在貓乳癌治療的有效性與毒性,同時分析可能影響預後的因子。
本研究以前瞻性的方式收集了於西元2016年六月起在國立臺灣大學生物資源暨農學院附設動物醫院透過組織病理學或細胞學確診為惡性乳癌並且使用必諾賓為第一線化療的患貓,記錄其病歷資料與治療過程及其反應,另外以回溯性的方式收集了在國立臺灣大學生物資源暨農學院附設動物醫院中,西元2014年至2017年罹患乳癌、並以艾黴素作為其第一線化療的患貓其病歷資料作為艾黴素組,分析兩組間腫瘤與病患特徵分佈、治療效果、與毒性是否有統計顯著性差異,同時對所有病患評估可能的預後因子的影響。 研究最終收集了26個案例,其中7隻患貓為必諾賓組,19隻為艾黴素組,兩組在腫瘤特徵與臨床分期分佈上無顯著差異,但兩組都將近有60%的患貓為臨床分期第四期的病患,在效果的部分,必諾賓組的反應率為75%,而艾黴素組為18%;生物反應率的定義在本研究為病患在接受化療時,曾經因為化療藥物而導致腫塊消退、維持穩定或保持無巨觀腫塊的比例,必諾賓組的生物反應率為100%,艾黴素組則為42%,兩組在生物反應率有顯著差異。必諾賓組的中位腫瘤惡化時間(Time to progression)為115天,而艾黴素組為102天,兩組無顯著差異 (P =0.949);而在中位存活時間的分析當中,必諾賓組為352天,艾黴素組為284天,兩組亦無顯著差異(P =0.948)。然而在毒性的部分,必諾賓組的嘔吐發生率顯著地低於艾黴素組(P =0.004),且食慾不振的發生率亦顯著小於艾黴素組(P <0.001);白血球低下的骨髓毒性則顯著的在必諾賓組較高(P <0.001),但沒有發生敗血症或與白血球低下相關的任何臨床症狀。預後因子分析的結果顯示,單變數與多變數分析中,會造成腫瘤惡化時間縮短的因子為已絕育的母貓罹患乳癌與對於化療無生物反應之患貓(Non-biological responders);對於化療無生物反應在單變數與多變數分析中均顯示有較短的存活時間,而腫塊出現潰瘍僅在多變數分析中顯示會縮短存活時間。 本研究的結果指出,必諾賓與艾黴素對於貓癌的治療效果相似,雖然使用必諾賓較可能出現白血球低下的副作用,但在本研究中白血球低下並沒有導致任何相關臨床症狀,且必諾賓有更低的消化道毒性,因此必諾賓或許更適合用在貓乳癌的化療當中,此外,罹患乳腺腫瘤時絕育的狀態、腫塊是否潰瘍與對化療是否有生物反應則為本研究的預後因子。 Feline mammary carcinomas (FMC) are the third most common cancer in cats. For those cats with large primary tumors, histological high grade tumors, evidence of lymphatic or vascular invasion, lymph node or distant metastasis, surgery alone is rarely effective and curative. Adjuvant chemotherapy is often recommended to improve outcome. Doxorubicin (DOX) is the most commonly used chemotherapy agent for mammary carcinoma. However, it is still lack solid evidence of survival benefit from adjuvant doxorubicin therapy. In addition, doxorubicin can be nephrotoxic to cats and often cause gastrointestinal disturbance. Vinorelbine (VRL) is a semisynthetic derivative of vinca alkaloids and can widely distribute in most tissues, especially in lung. In human, vinorelbine can be also used to treat breast cancer. Therefore, the purpose of this study is to compare the efficacy and toxicity of vinorelbine and doxorubicin in FMC. Possible prognostic factors for FMC were also investigated. Cats diagnosed with FMC histologically or cytologically and had been received doxorubicin or vinorelbine as their first-line chemotherapy at National Taiwan University Veterinary Hospital (NTUVH) animal cancer treatment center were enrolled into this study and the patient were divided into VRL group or DOX group. Cats in VRL group were enrolled prospectively since June, 2016 and cats in DOX group were collected retrospectively from 2014 to 2017 at NTUVH animal cancer treatment center. Total of twenty-six cats were divided into the two groups based on their initial treatment. Seven cats received vinorelbine as their first-line chemotherapeutic agent and were assigned to the VRL group; nineteen cats receiving doxorubicin as their first-line chemotherapeutic agent and assigned to the DOX group. No significance in distribution of tumor characteristics distribution and clinical stage in the two groups. Approximately 60% of patients were classified as clinical stage 4 in both groups. Response rate of VRL group and DOX group was 75% and 18% respectively. Biological response rate was defined as the percentage of cats had been experienced complete or partial remission, stable disease and Non-CR/non-PD in this study. Biological response rate was 100% for VRL group and 42% for DOX group, which was statistical significant. Median time to progression was 115 days for VRL group and 102 days for DOX group, which was not statistically significant (P =0.949). Median survival time was 352 days for VRL group and 284 days for DOX group, but no significant difference was noted (P =0.948). However, the incidence of vomiting and anorexia were both significantly higher in DOX group (P =0.004 and <0.001, respectively). Although the incidence of neutropenia was significantly higher in VRL group, no evidence of sepsis or clinical signs related to neutropenia was observed. As for the results of prognostic factor analysis, intact females and biological responders were both significantly associated with longer time to progression in univariate and multivariate analysis. Ulceration of tumor was correlate to worse survival only in multivariate analysis. Biological responders had significantly longer survival in both univariate and multivariate analysis. In conclusion, the efficacy of vinorelbine was similar to doxorubicin but much less gastrointestinal toxicities observed in cats treated with vinorelbine. Therefore, vinorelbine may be more appropriate to use as adjuvant chemotherapy in FMC. |
URI: | http://tdr.lib.ntu.edu.tw/handle/123456789/1278 |
DOI: | 10.6342/NTU201800511 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 臨床動物醫學研究所 |
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