比較晚期非小細胞肺癌病人有無接受維持性愛寧達化學治療對其存活期與生活品質之影響

前言：無論國內外，肺癌儼然是人類健康最大的威脅之一；尤其於台灣已連續蟬聯癌症死亡第一位，其中以非小細胞肺癌（non-small-cell lung cancer, NSCLC）之肺腺癌佔為其中最大的族群，且超過65%病人在診斷時已經是遠端轉移之末期。依據美國國家癌症資訊網(National Comprehensive Cancer Network, NCCN)之肺癌照護指引建議，無論有無基因突變的病人，其治療處方最終會進入愛寧達化學治療直至無法負荷治療或直至死亡，目的為延長其存活期；然而研究發現，愛寧達治療其無惡化存活期平均為六個週期之化學治療，且其副作用也開始增加繼而衝擊病人的生活品質；此外，迄今針對愛寧達治療週期亦未有一致定論。研究動機為探討維持性化學治療是否對病人之存活期有顯著延長，以及對其生活品質之影響？因此本研究目的為比較病人接受愛寧達六個週期治療與維持性治療對其存活期以及生活品質之影響，以供提出未來實證性的照護建議。研究目的：比較晚期非小細胞肺癌病人接受維持性愛寧達化學治療對其存活期與生活品質之影響。研究方法：本研究採前瞻性（prospective study）、類實驗性（quasi-experimental study)設計。研究對象為南部某醫學中心之胸腔科及血腫科病房、門診之非小細胞肺癌病人，接受鉑金類（Cisplatin或Carboplatin）加愛寧達（Pemetrexed）4個週期治療後，經影像學檢查、胸腔科醫師或放射科醫師判定無疾病惡化後均分為兩組，實驗組17人，對照組18人(N=35)。實驗組為只接受六次愛寧達治療、對照組則使用維持性愛寧達至疾病惡化，利用縱貫性追蹤方式比較維持性治療是否能有意義延長疾病惡化時間；除此之外，我們利用問卷調查（EQ-5D、EORTC QLQ-C30、EORTC QLQ-LC13、WHOQOL-BREF）比較兩組治療週期對生活品質影響及藥物相關不良反應之差異。研究結果：兩組受試者之人口學及臨床資料在影響預後因子上並無差別，研究數據亦顯示兩組之無惡化存活期無顯著差異(p=.51)；但是兩組受試者無惡化存活期與健康效用值比較，似乎實驗組比對照組來的好；藥物相關不良反應部份，對照組的grade 2副作用比實驗組多。結論：研究結果顯示兩組無惡化存活期相當，但實驗組的病人生活品質較好、藥物相關副作用少。因此，建議針對晚期之非小細胞肺癌病人於維持治療之選擇時具體運用SDM於晚期維持治療之選擇意願，讓病人於存活與生活品質間有更好權衡。

關鍵字

非小細胞肺癌；生活品質；無惡化存活期；存活期；愛寧達；藥物不良反應

並列摘要

Introduction: Lung cancer is certainly one of major threats to humankind regardless in domestic or foreign. It has been the leading cause of cancer death for consecutive years in Taiwan. Lung adenocarcinoma is the currently most common type of Non-Small Cell Lung Cancer(NSCLC), above 65% of which was founded distant metastasis when first diagnosis. According to National Comprehensive Cancer Network (NCCN) clinical practice guidelines, whether the gene mutation or not, the therapeutic plan finally leads to chemotherapy with Pemetrexed to extend the overall survival until intolerance or death. However, average six cycles Pemetrexed to achieve progression-free survival accompanied with poor quality of life due to its adverse effect. Besides, there has not been final conclusion to determine the cycles of Pemetrexed. To discuss whether the maintenance therapy has significant impact on lengthening survival period and quality of daily performance status or not is important. Hence, our research compares the overall survival and quality of life for patients received six cycles of Pemetrexed and maintenance therapy, which may provide the recommendation for further developing evidence based clinical practice guideline application. Purpose: Compare end-stage NSCLC patient’s overall survival and quality of life, who received six cycles pemetrexed or maintenance therapy. Method: our study is a prospective, quasi-experimental study. Cases include pulmonary medicine and oncology ward inpatients and oncology outpatients from one medical center in southern Taiwan. They underwent 4 cycles of platinum.-based drugs (Cisplantin or Carboplantin) plus Pemetrexed, radiography examination, whom then diagnosed progression-free by pulmonologist and radiologist. After, they were divided equally to two groups, 17 peoples in experimental group and 18 peoples in control group.(N=35) Cases in experimental group received only six cycles Premetrexed. Otherwise, cases in control group received maintenance Premetrexed until progressive disease. We used longitudinal survey to figure out whether maintenance therapy extends progression-free time. In addition, questionnaire survey (EQ-5D, EORTC QLQ-C30, EORTC QLQ-LC13, WHOQOL-BREF) was conducted to compare the discrimination of adverse drug reactions and effects of Quality of Life between two groups. Results: There is no demographic or clinical difference in two groups population. Our data also indicates no significant difference in progression-free survival between two groups.(p=0.51) Nevertheless, progression-free survival and health-related quality of life in experimental groups is better than control group. As for adverse drug reaction, grade 2 side effect in control group is more than experimental group. Conclusion: Our research illustrates the progression-free survival in two groups is equal. However, the quality of life is better and less adverse drug reactive was noticed in experimental group. Hence, we recommend the Shared Decision Making(SDM) to determine the therapy for end-stage NSCLC patients, which lets patients weigh the pros and the cons between survival and quality of life properly.