心率變異性分析是一項有用的、簡便迅速無侵入性且不昂貴的檢 查，心率變異性分析可進一步分析自主神經之影響或間接推斷臨床上之 效果，利用此本實驗應用心率變異性分析來評估非小細胞肺癌患者服用 艾瑞莎或得舒緩膜衣錠前後之心率變異性變化短時間並無差異，長時間 服用藥物可能會造成副交感活性增加。從本試驗初步看來，並沒有證據 顯示艾瑞莎和得舒緩膜衣錠有心臟毒性或影響。但卻發現長期使用似乎 會造成自主及副交感神經活性增加，皮膚副作用與副交感神經活性較為 正相關，間接推斷產生較好的臨床反應。當然這前後因果關係尚無法由 此實驗證實，但已發現心率變異性分析在此藥物治療可扮演一定的角 色。另外基因突變對於藥物治療和自主神經的活性影響似乎有一定的角 色。由於皮膚副作用與藥物反應和疾病預後呈相關，關於心率變異性分 析的臨床應用未來還需要更進一步之實驗支持。
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附錄一 "達楷" 隨身簡易型心電圖機實照
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附錄二 "達楷" 隨身簡易型心電圖機衛生署許可證
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附錄三 德國萊因TÜV認證
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附錄四
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附錄五
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Abstract
Gefitinib and erlotinib, both belong to epidermal growth factor receptor (EGFR) inhibitors, are tyrosine kinase inhibitors, which have well-tolerated clinical effect in patients with non-small-cell lung carcinoma, particularly to orientals and Asians. However, some traditional chemotherapy or target therapy to cancers have the adverse effect to patients, including cardiac and skin toxicity. The cardiac toxicity induced by EGFR inhibitors, including imatinib mesylate, dasatinib, nilotinib, sunitinib, sorafenib and lapatinib, are irreversible, except for gefitinib and erlotinib from researches recently.
Besides, most patients received the EGFR inhibitors therapy would produced skin toxicity, that was suggested to have a better response to treatment in patients with more severe cutaneous toxicity.
Heart rate variability (HRV) is used to evaluated the autonomic activity according to the heart rhythm analysis, which is used to predict mortality in heart facilure patients, cardiomyopathy and renal failure, sudden death and cardiac death in apparently healthy individuals. It is also an important research for cardiac toxicity related to drugs. It already related to the change of HRV after taking antipsychotic or anti-depressant medications. Cardiac toxicity of anthracycline also has good predictability via HRV analysis.
The experimental application of heart rate variability analysis to assess the changes of heart rate variability to the gefitinib and erlotinib, or the relationship ot the cardiac or skin toxicity. From the current study, there were no evident showing cardiac impact to gefitinib and erlotinib. However, prolong usage seemly to increase the autonomic or parasympathetic tone, which related to the skin toxicity and better clinical effects. The causal relationship, of course, are not definitely defined from current study. Heart rate variability wound play a role in these kind of therapy. Besides, genetic
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mutation also plays an important role to the pharmacological therapy and autonomic impact. Due to the skin adverse effect are related to the clinical effect or drug therapy, the clinical application of heart rate variability should be supported by further study.
Keywords: epidermal growth factor receptor inhibitor, erlotinib, gefitinib, heart rate variability, heart toxicity, skin toxicity.
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