- 學位論文
轉移性大腸直腸癌使用FOLFIRI化療組合藥物，在不同Irinotecan劑量合併Bevacizumab治療方案生活品質與成本效用：前瞻性兩年世代研究
Quality of Life and Cost Utility Analysis of Different Dose Irinotecan Plus Bevacizumab in Metastatic Colorectal Cancer：A Two-year Prospective Cohort Study.
摘要
研究目的 轉移性大腸直腸直腸癌經由UGT1A1基因檢查後，使用FOLFIRI化療組合藥物，在不同Irinotecan劑量合併Bevacizumab治療方案中進行藥物調整，可達到最佳治療效果，因此，本研究針對轉移性大腸直腸癌，透過不同Irinotecan劑量治療方案，探討病患治療後兩年內生活品質之改變趨勢及影響因子，進而評估不同Irinotecan劑量是否具有成本效用。 研究方法 本研究是前瞻性世代研究，針對南部某醫學中心於2015年10月至2020年4月共196位受試者，依照治療方案分為標準劑量組(未進行基因檢測，Irinotecan施打180mg/m2)及提高劑量組(有基因檢測，型態為：UGT1A1*1*28 Irinotecan最高施打到240mg/m2；有基因檢測，型態為UGT1A1*1*1，Irinotecan最高施打到260mg/m2)，兩組進行治療前、治療後六個月、一年及兩年追蹤評估，生活品質問卷包含：SF-36、FACT-C、EQ-5D-3L、BDI及BAI，並將所有自變項及依變項透過治療權重倒數機率(Inverse Probability of Treatment Weighting, IPTW)方法進行兩組樣本配對，接著利用廣義估計方程式(GEE)探討病患治療後兩年內生活品質之長期趨勢分析與重要影響因子，最後利用醫療相關直接成本及品質調整存活年，以決策樹進行成本效用分析。 研究結果 轉移性大腸直腸癌病患兩組治療後兩年內生活品質皆有顯著改善(P<0.05)，但在第六週生理功能皆顯著下降，到第二年提高劑量組改善幅度優於標準劑量組；控制時間因素，年齡、婚姻、抽菸、喝酒、治療前生活品質是病患治療後兩年內生活品質之顯著影響因子(P<0.05)；在成本效用分析，提高劑量組病患其醫療總成本為新台幣1,591,817元，品質調整存活年(Quality-Adjusted Life Year, QALYs)為1.88，標準劑量組病患其醫療總成本為新台幣1,498,563元，品質調整存活年為1.65，提高劑量組相對於標準劑量的遞增成本效用比(Incremental Cost-Utility Ratio, ICER)為新台幣412,205/QALY，在願付價格(Willingness to Pay, WTP)設定為801,037元的條件下(一倍國民生產毛額Gross Domestic Product, GDP)，提高劑量組是非常具成本效用優勢的決策選擇。 結論及建議 轉移性大腸直腸癌透過基因檢測並使用提高Irinotecan劑量是具成本效用優勢的，為了能夠使決策結果可以客製化，並建議轉移性大腸直腸癌若能在施打irinotecan劑量前，依據病人基因型態給予不同劑量，以符合成本考量與經濟效益將能夠提高成本效用，使醫療資源能夠更適當運用，藉此提供衛生單位、學術單位、醫療供給單位於治療轉移性大腸直腸癌之參考。 關鍵詞：轉移性大腸直腸癌、個人化醫療、生活品質、成本效用
並列摘要
Objective After UGT1A1 genetic examination for metastatic colorectal cancer, FOLFIRI combined with Bevacizumab treatment plan is used to adjust the drug in different Irinotecan doses to achieve the best medical outcomes. Therefore, the study purposed to explore the impact of different Irinotecan doses regimens in metastatic colorectal cancer patients on quality of life within and to evaluate whether different doses of Irinotecan can grasp the balance between cost and utility. Methods This prospective cohort study has recruided 196 metastatic colorectal cancer infarction patients from Oct 2015 to Apr 2020 in a southern medical center in Taiwan. The SF-36, FACT-C, EQ-5D-3L, BDI, and BAI quality of life measures were evaluated at baseline, the 6th month, 12th month, and 24th month after treatment. Inverse probability-of-treatment weights (IPTW) were used to obtain estimates of the mean associations of variables assessed with different Irinotecan doses regimens (high dose vs. standard dose). The generalized estimation equation (GEE) model also was employed to evaluate the longitudinal trend and risk factors of quality of life. A cost-utility analysis finally was performed by using TreeAge decision tree model. Results Both regimens of metastatic colorectal cancer patients had a significant improvement in quality of life after two-year treatment (P<0.05). Compared to the baseline, physiological function decreased significantly at the 6th month, but, compared to the 1st year, the quality of life measures showed significant improvement in high dose regimen compared to standard dose regimen at the 2nd year (P<0.05). Furthermore, age, marriage, smoking, drinking, quality of life before treatment are the significant factors associated with all quality of life measures during the study period (P<0.05). Additionally, the total direct medical cost of high dose regimen was higher compared to standard dose regimen and the incremental cost-utility ratio (ICUR) for high dose regimen compared to standard dose regimen was NT$412,205 per quality-adjusted life year (QALY) gained. Conclusions and Suggestions Through genetic testing, compared to standard high dose regimen, high dose regimen showed a cost effectiveness advantage in metastatic colorectal cancer patients. In order to make the best decision, it is recommended that metastatic colorectal cancer patients should be based on the patient's genotype before the irinotecan dose is administered. Different irinotecan doses given to meet cost considerations and economic benefits will increase cost-effectiveness and provide more appropriate regimen of medical resources in the treatment of metastatic colorectal cancer. Keywords：Metastatic Colorectal Cancer，Quality of Life ，Cost Utility Analysis
參考文獻
延伸閱讀
- 朱彥蓉（2017）。轉移性大腸直腸癌病患以UGT1A1基因多型性作為Irinotecan劑量提高前瞻性分析與生活品質之研究〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-1807201714100100
- Chou, T. H., Chang, K. J., Liang, J. T., Huang, J., & Lee, P. H. (2008). 大腸癌之輔助性化學治療：一項運用Oxliplatin加上5-Fluorouuracil及Leucovorin前瞻性之第二階段臨床試驗. 中華民國癌症醫學會雜誌, 24(4), 205-211. https://doi.org/10.6588/JCOS.2008.24.4.1
- Tsang, W. K., Chiang, J. M., & Changchien, C. R. (2005). 對轉移性之大腸直腸癌門診病患給予每週低劑量之CPT-11合併使用Tegafur-Uracil與Leucovorin治療. 中華民國大腸直腸外科醫學會雜誌, 16(4), 121-126. https://doi.org/10.6312/SCRSTW.2005.16(4).09417
- Li, K. L., Tsai, H. L., Su, W. C., Huang, C. W., & Wang, J. Y. (2021). 針對Regorafenib治療無效的轉移性大腸直腸癌，調整後的TAS-102服藥方式可有效降低藥物副作用. 中華民國大腸直腸外科醫學會雜誌, 32(4), 191-199. https://doi.org/10.6312/SCRSTW.202112_32(4).11022
- 溫崇宇（2006）。An Analysis of Health-Related Quality of Life and Medical Cost of Chronic Hepatitis C Patients under Different Treatment Strategies – A Case Study of a Medical Center〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2006.01295