胃癌患者的化學治療模式及其存活率之探討

Chemotherapy Treatment Patterns and Survival Outcomes among Gastric Cancer Patients

洪婉瑄(Wan-Hsuan Hung)

指導教授 ： 楊奕馨

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2016年)

摘要

背景
胃癌是世界上第五常見的癌症，且為死亡率第三高的癌症。在台灣，胃癌亦是第五常見的癌症，同時為前十大致死的癌症之一。在台灣，因為全民健保給付規範的緣故，胃癌化療用藥組合的模式可能會和世界各國有所差異，因此，本研究的研究目的為探討台灣治療胃癌的化療用藥組合的使用模式，並且進一步探討不同化學用藥組合和存活率之間的關係。
方法
本研究的研究設計為回溯性世代研究，以特殊需求申請的台灣全民健康保險研究資料庫中的癌症病人檔進行分析研究。本研究納入自2003至2011年間，大於18歲且初次被診斷為胃癌的病患，進一步歸納病人的化療用藥組合的使用模式，並分為接受手術後化療的病人群以及單獨接受化療的病人群兩群。再進一步利用Kaplan-Meier estimates 得到兩組中不同化學用藥組合的整體存活率(overall survival)；並且利用Cox迴歸分析 (Cox regression)調整所有變項後，得到使用不同化學用藥組合對於病人整體死亡率(all-cause mortality)之風險比(hazard ratios)。
結果
本研究總共納入了11,007位初次診斷為胃癌的病人，其中1,562位接受過手術治療之後所使用的化療藥物是健保給付適應症為術後輔助化學治療藥物的病人，4,333位接受過手術治療後所使用的化療藥物是健保給付適應症為緩和性化學治療藥物的病人，以及4.290位僅接受化療的病人。在接受術後輔助化學治療藥物、術後緩和性化學治療藥物以及單獨接受化療的胃癌病人中，使用頻率最高的為fluoropyrimidine-base 單獨使用(F)，其次為fluoropyrimidine-base 合併使用platinum-base (FP)化療組合。在接受手術後輔助化學治療藥物胃癌病人中，etoposide合併使用fluoropyrimidine-base (EtoF) 的化療用藥組合，相較於其他用藥組合而言，顯示了較高的一到三年整體存活率(overall survival)，分別為85.5%，70.6% 及67.6%。在手術後接受緩和性化療藥物的病人中，病人接受fluoropyrimidine-base合併使用polysaccharide-k (PSK)的化療用藥組合的中位數存活時間(median survival time)為6.3年，優於其他用藥組合。在單獨接受化學治療的病人中，單獨使用fluoropyrimidine-base化療藥物的病人三年整體存活率為14.8%，相較於其他化療用藥組合顯示出較佳的長期存活結果，但不具有統計顯著差異。
結論
本研究結果顯示，在台灣，對於胃癌病人的治療，使用頻率最高的化學治療藥物組合皆為單獨使用fluoropyrimidine-base化療藥物。在接受手術後輔助化學治療藥物的胃癌病人中，使用EtoF化療組合，有較佳的存活結果。此外，在手術後接受緩和性化療藥物的胃癌病人中，使用FK化療組合，相較於其他化療組合，顯示出較佳的存活結果。對於單獨接受化學治療的病人，所有化療組合不具有統計顯著性差異。

關鍵字

胃癌 ； 化學治療藥物使用模式 ； 存活率

並列摘要

Background
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer death worldwide. In Taiwan, gastric cancer is the fifth most common malignancy and the seventh most common cause of cancer-related deaths in 2012. Due to the reimbursement policy for gastric cancer chemotherapy in Taiwan, the chemotherapy usage patterns may be different from other countries. Therefore, our study aim is to investigate the chemotherapy treatment patterns in GC patients and to compare the survival outcomes of chemotherapy regimens for their effectiveness on mortality reduction of each regimen.
Methods
We conducted a retrospective population-based cohort study by analyzing the Taiwan Health Insurance Research Database (NHIRD). We included newly-diagnosed gastric cancer patients aged 18 years old or older during 2003‐2011. Patients who received chemotherapy were divided into postoperative chemotherapy and chemotherapy alone. We further computed overall survival (OS) rates of chemotherapy regimens by using Kaplan-Meier estimates. The Cox regressions were used to estimate the hazard ratios (HRs) and 95% confidence intervals after adjusting for covariates including gender, age, income, time to treatment and comorbidities.
Result
Totally, 11,007 patients are identified with newly diagnosed gastric cancer in this study. Among them, there are 1,562 postoperative patients receiving regimens which are reimbursed for adjuvant chemotherapy, 4,333 postoperative patients receiving regimens which are reimbursed for palliative chemotherapy, and 4.290 patients receiving chemotherapy alone. Fluoropyrimidine-base single agent (F) and fluoropyrimidine-base plus platinum-base (FP) regimen are the most common regimens in postoperative adjuvant chemotherapy and in postoperative palliative chemotherapy group and chemotherapy alone group. In postoperative adjuvant chemotherapy group, fluoropyrimidine-base plus etoposide (EtoF) regimen has better survival outcome. The 1-year, 2-year and 3-year OS are 85.5%, 70.6% and 67.6% respectively. In postoperative palliative chemotherapy group, fluoropyrimidine-base plus polysaccharide-k (PSK) regimen (FK) has better survival outcomes (median survival time: 6.3 years) than other regimens. For patients in chemotherapy alone group, fluoropyrimidine-base single agent has the best long-term survival than other regimens with 3-year OS of 14.8%, but the difference was not statistically significant.
Conclusion
In Taiwan, fluoropyrimidine-base single agent (F) and fluoropyrimidine-base plus platinum-base (FP) regimen are the most common chemotherapy regimens for GC patients. In postoperative adjuvant chemotherapy group, fluoropyrimidine-base plus etoposide (EtoF) regimen has better survival outcome. Besides, in postoperative palliative chemotherapy group, fluoropyrimidine-base plus polysaccharide-k (PSK) regimen (FK) has better survival outcome than other regimens.

並列關鍵字

gastric cancer ； chemotherapy usage patterns ； overall survival

參考文獻

1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.

2. Chiang CJ, Chen YC, Chen CJ, et al. Cancer trends in Taiwan. Jpn J Clin Oncol. 2010;40(10):897-904.

3. Yoon S, Yoo C, Ryu MH, et al. Phase 2 study of adjuvant chemotherapy with docetaxel, capecitabine, and cisplatin in patients with curatively resected stage IIIB-IV gastric cancer. Gastric Cancer. 2015.

4. Chiang C-J, Lo W-C, Yang Y-W, et al. Incidence and survival of adult cancer patients in Taiwan, 2002–2012. Journal of the Formosan Medical Association.

5. Kim R, Tan A, Choi M, et al. Geographic differences in approach to advanced gastric cancer: Is there a standard approach? Crit Rev Oncol Hematol. 2013;88(2):416-26.