晚期非小細胞肺癌患者使用標靶藥物與其他口服藥物交互作用之存活分析

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陳則穎(Tse-Ying Chen) 查詢紙本館藏

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工業管理研究所

論文名稱

晚期非小細胞肺癌患者使用標靶藥物與其他口服藥物交互作用之存活分析
(Survival analysis of target drugs and other oral drugs in patients with advanced non-small cell lung cancer)

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摘要(中)

近年來，用於治療晚期非小細胞肺癌的標靶藥物比例逐漸提高。在台灣常用的標靶藥物是得舒緩Erlotinib (Tarceva)和艾瑞莎Gefitinib (Iressa)。標靶藥物的治療成功將肺癌患者的治療方式帶入個人化領域。並非每個人都適合接受標靶藥物治療。隨著藥物的使用量增加，胃潰瘍的症狀是這些藥物最常見的不良反應。經常用一些制酸劑來緩解這些症狀，但這些藥物會改變腸胃道酸鹼值。一些研究指出酸鹼值會影響標靶藥物的吸收。除上述研究外，目前在分子生物學研究方面，有些研究認為特定疾病藥物能有效提高肺癌患者的生存率。如糖尿病常用的二甲雙胍(Metformin)。在有糖尿病的肺癌患者中，存活率高於非糖尿病患者的存活率。高血壓藥物血管張力素受體阻滯劑(ARB)可以提高肺癌患者的存活率。高血脂藥物（Statin類）可以提高肺癌患者的存活率。
在過去的研究中，沒有一個資料庫能完整蒐集患者的就醫紀錄。我們利用國民健保資料庫（NHIRD）的完整性去進行資料分析，國民健保資料庫的特點是長期追蹤、橫跨多個縣市。我們針對接受標靶藥物治療的非小細胞肺癌患者，進行存活分析，如常見的生命表(Life table)和Kaplan-Meier，探討制酸劑與三高口服藥物的藥物交互作用是否影響存活率，常用的統計方法有Log-rank檢定(Log-rank test) 和Wilcoxon檢定 (Wilcoxon test)，探討兩組治療方式之間的差異是否具有統計上的意義。

摘要(英)

In recent years, the proportion of target drugs used to treat advanced non-small cell lung cancer has increased. In Taiwan, the common target drug is Erlotinib (Tarceva®) and Gefitinib (Iressa®). The success of target therapy drugs brings the treatment of lung cancer patients to the field of personalization. Not everyone is suitable for receiving target drug therapy. With the increase in medication, the symptoms of gastric ulcer are the most common adverse reactions of these drugs. Often with some antacids to relieve these symptoms. However, these drugs will change the pH of the gastrointestinal tract. Some studies suggest that stomach PH affect the absorption of target drugs. In addition to the above research, the current molecular biology research, some studies suggest that specific disease drugs can effectively improve the survival rate of lung cancer patients. Such as diabetes commonly used metformin. In patients with diabetes mellitus, the survival rate is higher than that of non-diabetic patients. Hypertensive drug angiotensin receptor blockers (ARB) can improve the survival rate of lung cancer patients. Hyperlipidemia (Statins) can improve the survival rate of lung cancer patients.
In the past study, there was no database to collect the patient′s medical record. We use the integrity of the National Health Insurance Research Database (NHIRD) to do data analysis, the National Health Insurance Research Database is characterized by long-term tracking, across multiple counties. We conducted survival analysis of non-small cell lung cancer patients treated with target drugs, such as the common life table and Kaplan-Meier, to investigate whether the interaction of antacids with Hypertension, Hyperlipidemia, Diabetes oral drugs affects survival, commonly used statistical methods are log-rank test and Wilcoxon test to explore whether the difference between the two groups of treatment is statistically significant.

關鍵字(中)

★ 非小細胞肺癌
★ 存活分析
★ 標靶藥物
★ Kaplan-Meier法
★ 生命表法

關鍵字(英)

★ Non-Small Cell Lung Cancer
★ Survival Analysis
★ Target Drug
★ Kaplan-Meier Method
★ Life table Method

論文目次

摘要................................................................................................................................ I
Abstract ......................................................................................................................... II
Contents .......................................................................................................................IV
List of Table .................................................................................................................. V
List of Figures..............................................................................................................VI
Chapter 1 Introduction...................................................................................................1
1-1 Research background.......................................................................................1
1-2 Research motivation ........................................................................................2
1-3 Research objectives .........................................................................................4
1-4 Research environment .....................................................................................5
1-4-1 National Health Insurance Research Databases (NHIRD)...................5
1-4-2 Non-small cell cancer (NSCLC) types and treatment..........................8
1-4-3 Clinical study criteria ...........................................................................9
Chapter 2 Literature review .........................................................................................12
2-1 EGFR-TKIs and antacid drug interaction......................................................12
2-2 Hypertension, Diabetes, Hyperlipidemia and EGFR-TKIs drug interaction.14
2-2-1 Hyperlipidemia...................................................................................14
2-2-2 Diabetes..............................................................................................16
2-2-3 Hypertension ......................................................................................19
Chapter 3 Methodology ...............................................................................................21
3-1 The three important concepts of survival analysis ........................................24
3-1-1 Censored data.....................................................................................24
3-1-2 Survival Function...............................................................................25
3-1-3 Hazard Function.................................................................................26
3-2 Nonparametric methods for comparing survival distribution........................27
3-2-1 Log rank test.......................................................................................28
3-2-2 Wilcoxon test......................................................................................29
3-3 Kaplan-Meier method....................................................................................29
3-4 Life table method...........................................................................................36
Chapter 4 EGFR-TKIs and PPIs drug interaction........................................................42
Chapter 5 EGFR-TKIs and Diabetes drug interaction.................................................57
Chapter 6 EGFR-TKIs and Hypertension drug interaction .........................................73
Chapter 7 EGFR-TKIs and Hyperlipidemia drug interaction......................................90 Chapter 8 Conclusion and future research .................................................................98
Reference ...................................................................................................................101

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指導教授

曾富祥、枋岳甫(Fu-Shiang Tseng Yueh-fu Fang)

審核日期

2017-7-19

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