貓轉移性乳腺癌使用必諾賓或艾黴素治療效果之比較

Abstract

貓的乳腺腫瘤有高的比例為惡性乳腺癌，早期的肺臟轉移是造成患有乳腺癌 的貓咪死亡的主要原因。艾黴素是目前最常使用的化療藥物，然而目前的研究對 於有轉移的貓咪乳腺癌，使用化療的治療效果還沒有共識。必諾賓在人類乳癌的 研究顯示，其為一個有療效且副作用可承受的一個化療藥。然而在貓咪乳腺癌的 研究中，過去的文獻沒有研究在有肺臟轉移的貓咪使用必諾賓的療效。因此，本 篇的目的是，針對有乳腺癌並且有淋巴結轉移或肺臟轉移的貓咪，分析使用必諾 賓或者艾黴素的治療效果。 本篇論文為回溯性研究，回顧自 2011 年 1 月起至 2020 年 2 月止的台大動物 醫院的病歷，納入經由組織病理檢查或細胞學檢查確診為貓乳腺腫瘤的病例，每 隻貓至少接受一劑的必諾賓或者艾黴素治療，分別評估局部乳腺的團塊和轉移的 肺臟腫瘤，主要評估指標為存活時間(Survival time， ST)和無病惡化時間(Time to progression，TTP)，次要評估指標為無肺臟轉移病灶惡化時間(Time to lung progression，TTLP)和腫瘤的反應，包含客觀反應率(Objective response rate， ORR)、臨床受益率(Clinical benefit rate，CBR)。同時也分析副作用在兩種藥間 的差別，如:嗜中性白血球低下、腸胃道副作用、血中肌酐酸上升。 共有 32 隻貓納入，其中 21 隻貓接受艾黴素治療、11 隻貓接受必諾賓治療。 57.1%艾黴素組的貓在化療前有肺臟轉移，必諾賓組則有 81.8%。初步就診時有 15.6%的貓在 x 光診斷下有胸骨淋巴結腫大。治療結果如下:必諾賓組的貓其腫瘤 都沒有持續惡化，而 33.3%艾黴素組的貓出現惡化、41.7%艾黴素組內有肺轉移的 貓出現惡化。中位無病惡化時間在必諾賓和艾黴素組分別為 58 天和 62 天，而在 組內有肺轉移的貓分別為 60.5 天和 33.5 天。中位無肺臟轉移病灶惡化時間在必諾 賓和艾黴素組分別為 35 天和 95 天，而在組內原有肺轉移的貓分別為 49 天和 58 天。中位存活時間在必諾賓和艾黴素組分別為 211 天和 299 天，而在組內有肺轉 移的貓分別為 211 天和 285 天。這些評估時間在兩種藥都無顯著差異。 副作用結果如下:嘔吐是使用必諾賓最常見的副作用(72.7%)，接著是嗜中性白血球低下 (45.5%)、血中肌酐酸上升 (45.4%)、下痢 (36.4%) 及厭食 (27.3%)。 厭食的發生是唯一顯著比艾黴素少的副作用。使用艾黴素最常見的副作用是腸胃 道副作用(95.2%)，包含厭食 (81%)、嘔吐 (71.4%)、下痢 (14.3%)。血中肌酐酸上 升 (28.6%) 比必諾賓少發生但無顯著差異。所有使用艾黴素治療的貓都沒有出現 嗜中性白血球低下。 總結，在患有乳腺癌且轉移的貓，雖然在延長無病惡化時間和存活時間的方 面，必諾賓無法比艾黴素達到更加延長的效果，不過必諾賓的臨床受益率比艾黴 素好，顯示必諾賓至少有和艾黴素相當的治療效果。

Feline mammary gland tumor (MGT) has a high percentage to be malignant carcinoma. Early lung metastasis is the leading cause of death for these patients. Doxorubicin is the most commonly used chemotherapeutic agent to treat feline MGT. However, current studies have not reached a consensus on the efficacy of chemotherapy on feline MGTs with metastasis yet. Vinorelbine has been used in human advanced breast cancer as a tolerable and effective option. However, the efficacy of vinorelbine in feline MGTs with lung metastasis is not analyzed separately. Therefore, the goal of this study is to analyze the outcome of vinorelbine compared with doxorubicin in treating feline MGTs with lymph node or lung metastasis. Medical records from January 2011 to February 2020 from National Taiwan University Veterinary Hospital (NTUVH) were reviewed to include feline MGTs diagnosed by histopathology or cytology examination. Each cat receives at least one dose of doxorubicin or vinorelbine. The gross tumors of mammary glands and metastatic lesions in the lungs were both evaluated. Survival time (ST) as well as time to progression (TTP) were viewed as the primary endpoints of this study. Time to lung progression (TTLP) and response was used as the secondary endpoints. Adverse effects including neutropenia, gastrointestinal toxicities, and increased serum creatinine were analyzed. There were 32 cats enrolled in this study, including 21 cats in doxorubicin treatment and 11 cats in vinorelbine treatment. Lung metastasis occurred in 57.1% of cats in doxorubicin and 81.8% of cats in vinorelbine group before chemotherapy. Enlarged sternal lymph node was noted in 15.6% in the initial diagnosis. None of cats treated with vinorelbine experienced progression of MGTs while 33% of cats receiving doxorubicin experienced progression and 41.7% of cats with lung metastasis experienced progression. Median TTP was 62 days in doxorubicin group and 58 days in vinorelbine group; median TTP was 33.5 days in doxorubicin with lung metastasis and 60.5 days in vinorelbine group with lung metastasis. Median TTLP was 95 days in doxorubicin group and 35 days in vinorelbine group; median TTLP was 58 days in doxorubicin with lung metastasis and 49 days in vinorelbine group with lung metastasis. MST was 299 days in doxorubicin group and 211 days in vinorelbine group; MST was 285 days in doxorubicin with lung metastasis and 211 days in vinorelbine group with lung metastasis. There is no significance between two treatments in all kinds of follow-up time mentioned above. Vomiting (72.7%) was the most commonly seen adverse effect in vinorelbine, followed by neutropenia (45.5%), increased serum creatinine (45.4%), diarrhea (36.4%), and anorexia (27.3%). Anorexia was the only adverse effect that had significantly low occurrence compared to doxorubicin. Gastrointestinal toxicity (95.2%) was the most common side effect in doxorubicin group, including anorexia (81%), vomiting (71.4%), and diarrhea (14.3%). Increased serum creatinine (28.6%) was less common in doxorubicin group compared to vinorelbine. No cats in doxorubicin group experienced neutropenia. In conclusion, clinical benefits of vinorelbine were significantly better than doxorubicin in metastatic patients, though vinorelbine could not significantly prolong TTP and ST. This result indicates that vinorelbine is at least as effective as doxorubicin in treating metastatic feline MGTs.