轉移性結腸直腸癌化學治療之成本效果分析

目的: 轉移性大腸直腸癌的化學治療在過去的十年有長足，新藥如 oxaliplatin和irinotecan的加入，使得療效從原先以傳統單獨使用5-FU治療者得以倍增,但相對地成本也大幅增加，而大多數醫師及病患只著重療效和安全性,咸少注意治療的成本與效果的關係。隨著台灣健保局的財務日漸惡化，化療藥物的給付政策亦將緊縮，有必要針對轉移性大腸直腸癌化學治療之成本效果分析做專題研究。研究方法: 本研究為回溯性世代研究(Retrospective Cohort Study)，研究資料來源2004-2011年屏東基督教醫院的癌登資料庫和門診住院檔採病歷回溯性收集次級資料。本院轉移性大腸直腸癌接受過化學治療之病患臨床資料及醫療費用進行分析。包括依人口學、臨床及治療相關特徵進行描述性統計，比較三組化療處方之成本(化療藥費、門診、住院、總直接醫療費用和住院天數)及效果(無惡化存活期PFS和整體存活期OS) 。同時亦分析影響醫療耗用之預測因子及PFS,OS之預後因子。最後以增量成效比(ICER)將三組化療處方進行成本效果分析。研究結果顯示2003-2011九年間共有540例結直腸癌病患登錄在本院治療，其中轉移性病患並接受化學治療者共142例，平均年齡65歲，男女比：80/62。以化療處方類別分成三組: Xeloda、FOLFOX、FOLFIRI，這三組以人口學及臨床特徵比較除了Xeloda組平均年齡較大，FOLFIRI組較多接受標靶治療、診斷時第四期較多及血清白蛋白濃度大於3.5g/dl占多數外其他變項如性別、婚姻狀態、抽煙、嚼食檳榔、教育程度、ECOG體力狀態、身體質量指標BMI、血清腫瘤標記CEA、血色素值、有無接受手術、有無接受放療及察爾森共病指標在統計學上皆無差異。若以單因子變異數分析其直接醫療成本包括總化療藥費、總門診費用、總住院費用、總醫療費用及總住院天數三組皆有顯著差異：FOLFIRI >FOLFOX >Xeloda，若以效果分析包括整體存活期(OS)及無惡化存活期(PFS)則發現整體存活期三組在統計學上並無顯著差異；而另一方面無惡化存活期則FOLFIRI 比另外兩組顯著延長FOLFIRI> FOLFOX =Xeloda。至於醫療資源使用之預測因子分析，多變量線性回歸分析顯示影響最顯著還是化療處方的差異，其中以FOLFIRI花費最大，總醫療費用平均比Xeloda多耗用了新台幣428,680元。影響轉移性大腸直腸癌病患無惡化存活期，則以年齡超過75歲和較差體力狀態(ECOG≥1)為顯著不良預後因子;血清白蛋白濃度大於3.5g/dl預後較好。而整體存活期分析則呈現BMI(18.5-23)及血清白蛋白濃度大於3.5g/dl預後較好，而ECOG≥1仍是預後不佳之因子。至於成本效果分析方面，經由增量成本效果比(ICERs)分析，相較於另外兩組，平均每增一年壽命FOLFIRI耗用醫療成本仍是最多:比Xeloda多新台幣1,046,980元，比FOLFOX多新台幣273,962元。結論: 在單一區域醫院小樣本數的研究下, 三組化療成本具顯著差異，以FOLFIRI最多，而Xeloda最少;效果方面，則以FOLFIRI在無惡化存活期(PFS)顯著地優於另外兩組，但在整體存活期比較則三組並無統計學上差異。至於醫療資源使用之預測因子分析，化療處方為最顯著影響因子。而化療處方在統計學上則非顯著預後因子。最後分析三組化療之成本效果，FOLFIRI雖耗用較多醫療資源，若以從療效，社會及晚期結直腸病人的觀點，在三組化療中，為較具成本效果的處方。

關鍵字

成本；效果；化學治療；轉移性結直腸癌； Xeloda ； FOLFOX ； FOLFIRI

並列摘要

Purpose Chemotherapy for metastatic colorectal cancer (mCRC) has changed dramatically in the last decade. With the advent of newer agents such as oxaliplatin or irinotecan, there has been a paradigm shift in the treatment of patients with metastatic colorectal cancer with a doubling of median survival over 5-FU alone. However, Efficacy and safety rather than costs remain the major focus of both physicians and patients. In Taiwan, the increasing price of the newer drugs are altering and tightening the payment policy. Less is known regarding the cost-effectiveness of these agents among mCRC patients. Herein, we conducted this project to analyze cost-effectiveness chemotherapy for mCRC patients. Methods Retrospective analysis of mCRC patients receiving chemotherapy was performed using data from cancer registry data bank and medical records of Ping-Tung Christian Hospital during the year 2003 to 2011. The cohort was divided into 3 groups by the chemotherapy regimens of 1.Xeloda, 2.FOLFOX, and 3.FOLFIRI. Descriptive statistics were performed. Medical utilizations (chemotherapy, OPD, IPD, total medical costs, hospital days) and effectiveness [progression free survival (PFS) & overall survival (OS)] among the 3 regimens were compared. Predicting factors of costs utilization and prognostic factors of the cohort patients were analyzed as well. Incremental cost-effectiveness ratios ICERs among the 3 regimens were calculated. Results Total 540 colorectal cancer patients were treated and recorded in our data bank. There were 142 mCRC patients were enrolled into this study. All utilization including costs and hospital days among the 3 regimens showed significantly different. FOLFIRI regimen was the most costly one. In the multivariate regression analysis, chemotherapy regimen was the most significant impact factor of medical utilization in all costs and hospital days except OPD cost. Comparisons of effectiveness of PFS revealed that FOLFIRI was better than Xeloda significant statistically. No significant difference among the 3 regimens by Cox proportional hazard ratio and Kaplan-Meier survival analysis for OS model. Additional significant predicting factors of medical utilizations were age of 55-64 year-old in OPD cost and female gender in hospital days (13 days longer than male) respectively. As to the prognostic factors analysis, Cox hazard model disclosed older age (≥ 75) and poorer PS (ECOG≥1) were the poor prognostic factors in PFS. Good nutrition status (Alb>3.5g/dl) was the good prognostic factor for both PFS and OS analyses. Costs per life-year gained/loss for FOLFOX Vs Xeloda, FOLFIRI Vs Xeloda and FOLFIRI Vs FOLFOLX were -NT$499,057, NT$1,046,980 and NT$273,962 respectively. Conclusions Our study found that FOLFIRI regimen improved the PFS, however substantially increases direct medical costs compared with FOLFOX regimen and Xeloda in mCRC patients at Ping-Tung Christian Hospital. FOLFOX regimen costed more than Xeloda, but did not improved the effectiveness of both PFS and OS. The findings were generated from a single institute and small sample size cohort, in which the limitation should be noted.