以注射抗腫瘤因子抑制腫瘤生長之試驗性研究

Abstract

目前腫瘤占犬貓死亡原因的前十位，癌症治療仍有許多課題需要探討與研究。癌症始終具有極高的致死率，而致死原因不外乎癌症治療的限制及其他影響飼主積極治療意願的原因，例如化療與放射線治療的副作用、腫塊位置或大小影響手術邊界等等。而針對腫瘤的新穎療法正是當前熱門的治療方向，從腫瘤的發生與分化引導我們研發出新穎的藥物來治療腫瘤，因此對抗腫瘤的專一性提高且副作用降低。在此初探性研究中，我們以腫瘤內注射的方式給予ON B10藥物，來提高腫瘤內的藥物濃度，進而探討ON B10的治療效果，主要評估腫塊的消退率與疾病進展空窗期的長短。ON B10為每福敏、阿斯匹靈與血清素的複合藥劑。最終完成試驗的有15頭患有至少一個皮膚腫塊的犬隻，其中5頭為肉瘤類腫瘤，7頭為上皮類腫瘤，另有3頭則分別不屬於上述兩類的腫瘤。就目前初探性研究的結果來說，腫瘤的消退率平均可達35%；整體而言，又以上皮類腫瘤的反應較佳，可達72%。藥物的副作用則少見，可見有皮膚、消化道、神經、呼吸道及腫瘤疼痛等，評估方式依照獸醫癌症協會分級為準則，程度一與程度二的副作用分別占61%與18.8%，大部分為自限性的輕微不適。研究結果顯示藥物ON B10對於治療皮膚型腫瘤成效不錯且副作用低，日後相關研究則須著重於上皮類腫瘤，以期能在臨床上廣泛運用。

Cancer is one of the most important diseases that possess high mortality. Numerous attempts of novel therapeutic trials against tumor cells are still under extensive research investigation. Studies of carcinogenesis and tumor proliferation in molecular level are helpful for novel therapy advancement. Now we are using a combination of antitumor medications to inhibit tumor growth and induce tumor cell death. In this pilot study, the agent named ON B10 was injected intratumorally in order to allow high concentration built up inside the tumor mass and inducing greater tumor killing efficacy. It is important to assess tumor burden volume change which is a valid indicator of the treatment efficacy. In this study, we documented tumor shrinkage rate and disease progression-free interval as an indication of the endpoint of this clinical trial. Fifteen canine patients were enrolled in this study, including soft tissue sarcoma (5), epithelial cell origin tumor (7) and tumors of undetermined origin (3). The expected tumor volume reduction was shown in ten of the patients. Overall reduction rate was 35% and the most promising effect was noted in carcinoma group with average 72% tumor reduction rate. The toxicity was recorded and evaluated in five categories, including dermatologic, gastrointestinal, neurologic, respiratory and tumor pain reactions according to VCOG criteria. The administration of B10 formulation had induced mild toxicities in twelve patients that are all tolerable and self-limited (grade I, 61%; grade II, 18.8%). The results suggest this product can be used to inhibit tumor growth in clinical setting safely and warrant further study focused on carcinomas. Multiple factors affecting drug delivery and tumor responses are discussed.