臺灣博碩士論文加值系統

背景
大腸直腸癌在2015年是最常被診斷的癌症之一，其中約有20%病人診斷時已為轉移性大腸直腸癌，五年存活率僅12%。治療轉移性大腸直腸癌時，化學治療及標靶治療扮演重要角色。近年來，新的化學治療及標靶治療藥品陸續研發、核准上市，造成相關費用上升，因此，評估藥品的花費及經濟成本效益非常重要。
目的
利用衛生福利部資料科學中心之資料庫探討轉移性大腸直腸癌之治療模式、藥物治療之花費，研究轉移性大腸直腸癌病人之存活情形及評估其治療藥品之經濟成本效益。
方法
以台灣癌症登記檔、死亡登記及健保資料庫的資料，對2007~2014年間，20歲以上轉移性大腸直腸癌(ICD-O-3 code: C18~C20)病人進行研究。病人資料納入後，依其接受之治療模式分組，並計算其使用之藥品與其花費。且於KRAS未突變的次族群中比較四種藥品治療組合的ICER，進行經濟成本效益分析。

結果
研究族群由7,865位病人組成，包含2123位僅接受化學治療、1297位接受化療與標靶治療、2193位接受手術及化療、2252位接受手術、化療與標靶治療之病人。2007~2014年間，轉移性大腸直腸癌的病人藥品平均花費為419(千/每人)，而接受手術、化療及標靶治療的病人，以及KRAS未突變之病人，平均藥品花費較高。所有藥品中，irinotecan、oxaliplatin、bevacizumab花費最高，然而cetuximab於KRAS未突變病人之花費漸增，於2014年超越bevacizumab。四種治療組合中FOLFOX + bevacizumab花費最低，與之相比，使用FOLFIRI + cetuximab之病人，存活時間最長，且ICER符合經濟成本效益。
結論
治療KRAS未突變病人時，可優先考慮符合經濟成本效益的FOLFIRI + cetuximab。此研究結果可於臨床決策時提供更全面的思考面向，然分析經濟成本效益時亦應考慮藥品副作用、使用藥品之週程及後續住院頻率，因此，未來可進一步探討副作用對於生活品質的影響。

Background
Colorectal cancer (CRC) is one of the most commonly diagnosed cancer in 2015 globally. 20% of the patients were diagnosed as metastatic, and the 5-year survival rate for metastatic CRC (mCRC) is 12%. Chemotherapy and targeted agents are major sources of expenditure, and the introduction of new agents has caused an increase in treatment expenditures. Therefore, evaluating costs of medications and cost effectiveness are important.
Objectives
The study objectives are to investigate patterns of treatment, expenditure of pharmacotherapies, the survival outcome among mCRC patients, and cost-effectiveness of medications of mCRC.
Materials and Methods
Using data from Taiwan Cancer Registry and Taiwan National Health Insurance (NHI) Database, we conducted a population-based study. Patients aged over 20 with metastasis colorectal cancer (ICD-O-3 code: C18~C20) during 2007~2014 were included. The patients were further grouped according to their treatments (chemotherapy alone, chemotherapy + operation, chemotherapy + targeted therapy, chemotherapy + targeted therapy + operation), and their utilization and cost of anti-tumor agents were analyzed.
We also conducted analyses to compare incremental cost-effectiveness ratio (ICER) between different regimens among KRAS wild-type patients by dividing difference of mean cost per patient and the difference of mean survival time.
Results
There were 7,865 mCRC patients extracted as our study cohort between 2007~2014, which including 2123 (26.99%), 1297 (16.49%), 2193 (27.88%), and 2252 (28.63%) patients received C/T alone, C/T + T/T, C/T + OP, C/T + OP + T/T, respectively. The total expenditure of anti-tumor agents was NTD 3,294,525 (thousand) from 2007~2014, and it cost NTD 419 (thousand) for treating per mCRC patient. The sum and mean cost per patient was the highest in the C/T + OP + T/T group and KRAS WT patients. Irinotecan, oxaliplatin, and bevacizumab were the mostly common used agents, while in KRAS wild-type patients, the utilization of cetuximab became more than of bevacizumab in 2014. FOLFOX + bevacizumab was the least expensive regimen, and when compared to FOLFOX + bevacizumab, FOLFIRI + cetuximab had the longest survival time, and was recommended as very cost-effective according to WHO CHOICE plan.
Conclusion
Our results showed that FOLFIRI + cetuximab was shown to be very cost-effective among KRAS WT patients, which should be considered preferentially for feasible patients.
Our study provides a more comprehensive aspect when making clinical decisions, while the adverse events, length of the course, and subsequent hospitalization rates should also be considered, and more warranted studies are needed.

中文摘要 I
Abstract III
致謝 V
Chapter 1 Introduction 1
Section 1.1 Background 1
Section 1.2 Study objectives 3
Chapter 2 Literature Reviews 4
Section 2.1 Epidemiology of metastatic colorectal cancer 4
Section 2.2 Management of metastatic colorectal cancer 4
Section 2.3 Cytotoxic agents 5
Section 2.4 Targeted agents 6
Section 2.5 Patients with refractory disease 13
Section 2.6 Prognostic determinants that affect medication decision 14
Section 2.7 Cost-effectiveness from randomized controlled trials 17
Chapter 3 Materials and Methods 20
Section 3.1 Data source 20
Section 3.2 Study cohort 21
Section 3.3 Analysis variables 23
Section 3.4 Statistical analyses 27
Section 3.5 Cost-effectiveness Analysis 28
Chapter 4 Results 30
Section 4.1 Demographic characteristics of study cohort 30
Section 4.2 Expenditure of medication for metastatic colorectal cancer 32
Section 4.3 Drug utilization 33
Section 4.4 Survival analysis 35
Section 4.5 Incremental Cost-Effectiveness Ratio 37
Chapter 5 Discussion 40
Section 5.1 Treatment patterns of mCRC in Taiwan 40
Section 5.2 Expenditure of medications for mCRC 41
Section 5.3 Utilization of medications for mCRC in Taiwan 43
Section 5.4 Survival analysis 44
Section 5.5 Utilization of different regimens 46
Section 5.6 Incremental cost-effectiveness ratio (ICER) of regimens 47
Section 5.7 Strength and limitations 49
Chapter 6 Conclusion 51
References 106

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