復發的犬隻淋巴瘤中持續使用L-asparaginase的效果和毒性評估

Abstract

L-asparaginase (L-ASP)是一個細菌來源的酵素類化療藥物，此藥物在眾多抗癌藥物中優勢包括以下兩點：第一、藉由獨特的藥理機制去對抗腫瘤。因為L-ASP藥主要是藉由剝奪腫瘤細胞生長所必需的胺基酸，進而抑制蛋白質的合成來對抗腫瘤。第二、相較於其他藥化療藥物，L-ASP只有很輕微的骨髓抑制。根據之前的研究指出，在化療的最初加入L-ASP並不會有顯著的幫助。近年來很多獸醫的腫瘤科醫師建議L-ASP應留待腫瘤復發時再行使用。本篇研究的目的主要是探討在復發的犬隻多發性淋巴瘤中，連續性的加入L-ASP合併控制的效用及其可能帶來的毒性。而研究的結果將會再與之前未使用過L-ASP控制的病例 (對照組)比較，用以了解是否L-ASP對於整體的存活時間是否有延長的效用。共有40隻狗被納入本研究中，整體的反應率 (response rate) 為82.5%，而其中完全消退(Complete remission, CR)的比例為52.5%；部分消退 (Partial remission, PR) 的比例為30%。而持續治療到動物又再復發的時間 (Time to progression) 中位數為63天 days (範圍從17到778+天) 。而在持續治療的過程中，L-ASP合併其他藥物所帶來的副作用是很輕微的。和對照組相比，持續使用L-ASP並不能顯著的增加整體的存活時間。綜合以上結果，持續性合併使用L-ASP於復發的犬隻多發性淋巴瘤中是有效的再次誘導腫瘤消退的方法，在考慮其他更高毒性的療程之前，本療程可能是更好的選擇。

L-asparaginase (L-ASP) is an enzymatic chemotherapy agent derived from bacteria. There are two major advantages of using this drug which include unique pharmacologic mechanism (deprives tumor cells of that essential amino acid and inhibits protein synthesis) and very mild bone marrow suppression. According to previous studies, there are no significant benefits when L-ASP was used during the initiation of the treatment regime, however in recent years the use of L-ASP in relapsed lymphoma had been recommended by many oncologists. The purpose of this study is to exam the efficacy and toxicity associated with the addition of L-ASP into the treatment modality of relapsed canine multicentric lymphoma. The tumor response results were then compared with previous cases (control group) which have never receive any L-ASP treatment. Total of 40 dogs were included in the study. The overall response rate was 82.5% (52.5% CR, 30% PR), and median remission duration was 63 days (range, 17–778+ days). The side effects of L-ASP treatment were well- tolerated. Continuous L-ASP administration did not significantly prolong the overall survival time. In conclusion, the addition of L-ASP into the rescue protocol of relapsed canine lymphoma represents an effective re-induction method. This protocol may be a preferred rescue option before considering other treatment modality with higher toxicities.