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題 名 | 癌症病患之藥動學及藥效學研究=Pharmacokinetic and Pharmacodynamic Studies in Cancer Patients |
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作 者 | 韓景媛; 胡幼圃; | 書刊名 | 醫學研究 |
卷 期 | 13:2 1992.09[民81.09] |
頁 次 | 頁77-96 |
分類號 | 418.2216 |
關鍵詞 | 病患; 癌症; 藥效學; 藥動學; |
語 文 | 中文(Chinese) |
中文摘要 | 截至目前為止鼻咽癌之癒後仍不理想,在日本、臺灣及東南亞地區,鼻咽癌之發生率皆較其他地區為高,例如在中華民國臺灣地區之鼻咽癌發生率是每千萬分之4.82,且其癒後情形也不樂觀,5年存活率的病患只有34%。 抗癌化學藥物之治療指數,較其他一般之藥物狹窄,不論病患是否使用了過量之抗癌藥物,其產生之毒性都可能使生命受到威脅,因此癌症化學治療需要一個更精密且更可信賴之治療方法。 各種抗癌化學治療藥物用於不同癌症患者之個別藥物動力學性質,非但國內缺乏,國際上亦大都闕如,且抗癌藥物之理想治療濃度範圍尚未被建立,因此對於如何將藥物動力學及藥效學性質應用到癌症化學治療上,目前幾乎是不可能的。 Epirubicin在多種癌症上之治療已有廣泛研究,臨床試驗仍在持續進行,希望能在化學治療上尋找出一個理想的給藥方式及評估規則。在過去5到10年內有許多研究此課題的文獻發表,我們一一回顧其研究結果。發現目前有幾個不同的給藥計劃,例如:三周一次持續性的慢速靜脈輸注低劑量之epirubicin、一周一次持續性的慢速靜脈輸注低劑量之epirubicin及動脈給藥等化學治療法,這些給藥方式以epirubicin為例,其實驗數據都建議:也許這些給藥計劃會較傳統的每三週一次較高劑量的治療方法,使病患所產生之心臟毒性及急性毒性低,所以這些治療方式也許可提供一個較大的給予劑量。此外其他一些研究則朝著使用抗氧化劑來預防epirubicin所產生的毒性方向發展,一些研究學者已証實了以抗氧化劑合併抗癌藥物給予癌症動物,可使動物因抗癌藥物所產生之毒性降低,對動物之存活率亦有助益。 在我們經歷七年多的研究中,以成功的發展出了鼻咽癌病患之epirubicin"有效治療血漿藥物濃度"。換言之,若鼻咽癌患者接受75-110 mg/m² epirubicin快速靜脈輸注治療後,將可產生一與治癒具密切關聯性的藥物濃度範圍。研究發現當以epirubicin快速靜脈輸注治療時,使用之epirubicin的劑量,至少要能使患者之第72小時的血漿藥物濃度達到7ng/ml,其癒後情形應會較為樂觀。我們以病患之第72小時血漿藥物濃度及血漿清除率為基礎,調整病患epirubicin之治療劑量,已使鼻咽癌患者之反應率由52%提升至72%。以epirubicin的有效治療濃度範圍,結合臨床治療監測(therapeutic drug monitoring)將可提升鼻咽癌患者的存活率。 |
英文摘要 | The prognosis of NPC is known to be poor. The incidence of NPC is rather high in Japan, Taiwan, and Southeast Asia. In Republic of China on Taiwan, the incidence was 4.82/million and the prognosis is relatively poor (34% 5-year survival rate). Cancer chemotherapy agents have rather lower therapeutic indices than most other pharmacological agents. The difference between an underdose and an overdose is small and the consequences of either can be life-threatening. Therefore, cancer chemotherapy needs a precise and reliable therapeutic regimen. It is obvious that there are problems with pharmacokinetic individualization of cancer chemotherapy. The optimal therapeutic range for any given anticancer drug has not been established, therefore, it is not possible to give advice on how to use pharmacokinetic principles to establish individualized chemotherapy. Epirubicin has undergone extensive investigation in a wide variety of tumors. Cliical studies are continuing to define the optimal administration schedule and to assess its role in chemotherapy. Over the past 5 to 10 years, several reports on this subject have been published. These representative studies are thoroughly reviewed herein. Several different regimens are evaluated (e.g., weekly schedule, continuous infusion of low-dose epirubicin, and intraarterial chemotherapy). Since there are data with epirubicin suggested that these schedules may be less cardiotoxic and have less acute toxicity than the conventional 3 weeks schedule does. These schedules might allow a large dose per unit time to begin. Some experimental approaches have been developed to prevent that toxicity by the use of antioxidant agents. A number of investigators have demonstrated that the treatment of animals (e.g., mice) with an antioxidant agent provided a survival benefit to animals against its toxicity, and also an enhancement of its antitumor effect in tumor-bearing animals. According to our own seven years research, we have established an “optimal therapeutic plasma concentration” of epirubicin in nasopharyngeal carcinoma patients. In other words, we have identified a concentration range that is more frequently associated with therapeutic success in patients with the disease who have been treated with rapid infusion of 75-110 mg/m² epirubicin. Our data indicates that the dosage of epirubicin should be at least high enough to achieve a plasma concentration at 72 hr above 7 ng/ml when the drug is given as a rapid infusion. Increase the epirubicin for all patients appears to be a feasible alternative to adjusting dose in individual patients on the basis of plasma concentration at 72 hr and plasma clearance. Our recent studies further validate epirubicin optimaltherapeutic range for patients with nasopharyngeal carcinoma. This application of the principle of therapeutic drug monitoring (TDM) have markedly increased the response rate and survival rate. |
本系統中英文摘要資訊取自各篇刊載內容。