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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳燕惠 | |
dc.contributor.author | JIA-SHAN Chou | en |
dc.contributor.author | 周佳姍 | zh_TW |
dc.date.accessioned | 2021-06-17T01:36:22Z | - |
dc.date.available | 2022-09-08 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-01 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67532 | - |
dc.description.abstract | 研究背景: 治療多發性骨髓瘤的藥物中,傳統化療效果有限,新興藥品bortezomib可以改善病人存活率,因此廣泛用於治療多發性骨髓瘤病人。然而,周邊神經病變 (peripheral neuropathy)為多發性骨髓瘤病人使用bortezomib為主的療程常見之副作用,使得病人需要調整劑量、延緩治療甚至是停止使用藥品,對於病人的生活品質有負面的影響。因此許多研究致力於如何降低此項副作用的發生,其中皮下注射降低周邊神經病變風險以及相關危險因子之研究結果並不一致,台灣也缺乏相關之臨床資料。
研究目的: 本研究分析多發性骨髓瘤病人實際於臨床上使用bortezomib為主的療程產生之周邊神經病變發生率以及探討不同給藥途徑及其他相關危險因子對於周邊神經病變之影響。 研究方法: 本研究採回溯性世代研究,以臺大醫院的醫院資料庫及病歷系統作為研究材料。研究對象為多發性骨髓瘤病人,並於2006/4/1-2016/6/30期間接受bortezomib治療。所有病人皆以接受第一劑bortezomib之第一天當作「進入研究世代日期(index date)」,而後追蹤至病人發生周邊神經病變、死亡、失去追蹤、研究結束(2016/12/31)。計算周邊神經病變之粗發生率,方式為將事件數除以人年;使用治療權重倒數機率(inverse probability of treatment weighting, IPTW)降低選擇性偏差,校正其他干擾因子的影響,並使用Kaplain-Meier存活曲線以及Cox比例風險迴歸模式(cox-proportional hazards regression model)分析不同給藥途徑對於周邊神經病變之風險,再進一步使用次族群分析以及敏感度分析確認結果;危險因子評估部分則是以單變項及多變項cox比例風險迴歸模式分析,分析其他相關危險因子對於周邊神經病變的影響。 研究結果: 本研究共納入421位多發性骨髓瘤病人,其中224人使用靜脈注射,197人使用皮下注射,總共有47% 的病人發生周邊神經病變的副作用,以輕微(grade 1-grade 2)及感覺神經病變症狀為主。自進入研究世代日期至發生周邊神經病變之累積劑量為 20 mg,時間為2.7個月,大約為給予藥物2-3個周期後發生,其中皮下注射較長時間 (IV vs. SC, 2.25 vs. 3.77 months) 後才發生周邊神經病變以及累積較高劑量 (IV vs. SC, 18.18 vs. 24.75 mg) 。 周邊神經病變之粗發生率在靜脈注射為0.533/人年,皮下注射為0.407/人年,且周邊神經病變、腹瀉以及血小板低下的比率皆於皮下注射組較低。不論是Kaplain-Meier 存活曲線或多變項比例風險迴歸模式分析,使用bortezomib皮下注射給藥途徑都能夠顯著降低周邊神經病變之風險(HR=0.486, 95% CI=0.323-0.731, p=0.0005),以給藥頻次進行次族群分析以及敏感度分析仍有相似結果,皮下注射可以降低周邊神經病變之風險。 以單變項迴歸分析危險因子,病人於進入研究世代日期前有周邊神經病變之症狀,其接受治療後發生周邊神經病變之風險較高(HR=1.548, 95% CI=1.063-2.255); 若使用bortezomib-thalidomide(VT)為主之療程周邊神經病變之風險較低(HR=0.629, 95% CI=0.435-0.908)。然而若是以多變項迴歸分析,則是年齡大於75歲、帶狀皰疹病毒感染、進入研究世代日期前具有周邊神經病變症狀、糖尿病伴隨末端器官受損之病人顯著增加周邊神經病變之風險。 研究結論: 此研究中,觀察到實際應用皮下注射給藥途徑於臨床上,可以顯著降低周邊神經病變之風險。本研究發現多發性骨髓瘤病人使用以bortezomib為主療程所產生的周邊神經病變之危險因子為年齡大於75歲的病人、帶狀皰疹病毒感染、進入研究世代日期前具有周邊神經病變症狀、糖尿病伴隨末端器官受損,因此未來在這群高危險病人使用此療程時,應須做更謹慎的神經學評估,以降低此項副作用所帶來之負面影響。 | zh_TW |
dc.description.abstract | Background: The introduction of a proteasome inhibitor bortezomib has significantly improved response rates and overall survival in patients with multiple myeloma (MM), and it has soon become the cornerstone of treatment in both newly diagnosed and relapsed/refractory settings. However, peripheral neuropathy (PN) is a common adverse effect in MM patients treated with bortezomib, often requiring dose modifications, delayed treatment or discontinuation of bortezomib, which negatively affects clinical endpoints and quality of life. Therefore, there are a lot of studies that were dedicated to reducing the incidence of this adverse effect. However, there are no consistent findings regarding the risk factors that may cause PN. In addition, we try to understand whether subcutaneous (SC) administration can reduce PN incidence of bortezomib-based regimen in clinical settings.
Objective: This study aim to examine the incidence of PN in MM patients treated with bortezomib-based regimen and to analyze the impact of different administration routes on the occurrence of PN as well as the potential risk factors in clinical settings Methods: This is a retrospective cohort study with patients who were diagnosed with MM and initiated bortezomib-based regimen between April 1, 2006 and June 30, 2016 at National Taiwan University Hospital (NTUH) in Taiwan. We performed a retrospective chart review to collect clinical data. All patients were followed after the first dose of bortezomib (index date) until PN, death, loss to follow up or study end (December 31, 2016).We calculate the incidence of PN using events/person-year and use IPTW to reduce selection bias. Kaplain-Meier survival curve and cox-proportional hazards regression model were applied to examine the impact of different administration routes on the risk of PN. Furthermore, we use subgroup analysis and sensitivity analysis to confirm our results. Univariate and multivariate cox proportional hazards regression model were applied to examine the association between PN and other potential risk factors. Results: We identified 421 MM patients who included 224 patients receiving intravenous (IV) and 197 patients receiving SC administration. The rate of PN were 47%. Among patients who occurred PN, median cumulative dose to first onset of PN was 20 mg and median time to PN onset was 2.7 months, approximately 2-3 cycles of bortezomib. Median time to first onset of PN was longer (IV vs. SC, 2.25 vs. 3.77 months) and median cumulative dose was higher (IV vs. SC, 18.18 vs. 24.75 mg) in patients using SC than using IV administration. The incidence of PN for IV and SC administration was 0.533/person-year and 0.407/person-year, respectively. The rate of PN, diarrhea and thrombocytopenia were lower in the SC group. Kaplain-Meier survive curve and multivariate cox proportional hazard regression model showed that SC administration had lower risk of PN in MM patients treated with bortezomib-based regimen (HR=0.486, 95% CI=0.323-0.731, p=0.0005). Similar results were found in the subgroup and sensitivity analysis. Univariate cox proportional hazard regression model showed that baseline PN symptoms was associated with higher risk of drug-induced PN(HR=1.548, 95% CI=1.063-2.255)and VT-based regimen was associated with lower risk of PN (HR=0.629, 95% CI=0.435-0.908). In addition, multivariate cox proportional hazard regression model showed that age > 75 years, baseline PN symptoms, herpes zoster infection and diabetes (DM) with end organ damage were risk factors for PN caused by bortezomib-based regimen. Conclusions: Administration of SC bortezomib had lower risk of PN in “real-world” clinical practice. In addition, neurological exacerbation should be cautiously evaluated in patients with baseline PN symptoms, DM with end organ damage, herpes zoster infection and age >75 years to reduce the negative impact of PN induced by bortezomib-based regimen. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:36:22Z (GMT). No. of bitstreams: 1 ntu-106-R04451003-1.pdf: 2650229 bytes, checksum: e245ee90117782910d71068f7d4ef214 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 I
中文摘要 II 英文摘要 IV 表目錄 XI 圖目錄 XIII 縮寫對照表 XVIII 第 1 章 前言 1 第 2 章 文獻探討 2 2. 1 多發性骨髓瘤 2 2. 1. 1 多發性骨髓瘤之流行病學 2 2. 1. 2 多發性骨髓瘤之疾病成因 2 2. 1. 3 多發性骨髓瘤的臨床表徵與診斷條件 3 2. 1. 4 多發性骨髓瘤的分級 3 2. 1. 5 多發性骨髓瘤之治療 5 2. 1. 6 治療相關副作用 6 2. 2 Bortezomib 藥物介紹與副作用 7 2. 2. 1 Bortezomib作用機制 7 2. 2. 2 Bortezomib核准適應症 7 2. 2. 3 Bortezomib 藥物動力學性質 8 2. 2. 4 Bortezomib常用劑量 8 2. 2. 5 Bortezomib常見之副作用 8 2. 2. 6 Bortezomib 引起周邊神經病變之發生率 9 2. 3 周邊神經病變 10 2. 3. 1 周邊神經病變臨床表徵 10 2. 3. 2 周邊神經病變臨床分級 11 2. 3. 3 病理機制 11 2. 3. 4 周邊神經病變之處置 12 2. 4 Bortezomib 引起之周邊神經病變與其相關因素 13 2. 4. 1 給藥途徑 13 2. 4. 2 給藥頻率與累積劑量 16 2. 4. 3 危險因子 17 第 3 章 研究目的 19 第 4 章 研究方法 20 4. 1 研究材料 20 4. 2 研究族群與研究架構 21 4. 2. 1 研究族群之納入與排除條件 21 4. 2. 2 研究架構 22 4. 2. 3 研究期間定義 23 4. 2. 4 研究資料收集 23 4. 2. 5 研究變相定義 25 4. 3 次族群分析(subgroup analysis) 26 4. 4 敏感度分析(sensitivity analysis) 26 4. 5 統計分析 27 4. 5. 1 傾向分數(propensity score, PS) 27 4. 5. 2 研究族群之描述性統計分析 27 4. 5. 3 存活分析(Kaplain-Meier survival curve) 28 4. 5. 4 比例風險迴歸模式分析 (cox proportional hazard regression model) 28 4. 5. 5 統計軟體 29 第 5 章 研究結果 30 5. 1 研究族群的建立 30 5. 2 研究族群之背景資料分析 31 5. 2. 1 研究族群之背景資料描述 31 5. 2. 2 皮下注射與靜脈注射病人背景資料描述 32 5. 2. 3 經SIPTW校正後病人之背景資料描述 33 5. 3 給藥相關資料分析 40 5. 3. 1 給藥相關資訊 40 5. 3. 2 化學治療療程分析 40 5. 4 Bortezomib 相關療程之副作用分析 42 5. 5 給藥途徑對於周邊神經病變風險的影響 44 5. 6 給藥頻率對於周邊神經病變風險的影響 44 5. 7 次族群分析(subgroup analysis) 44 5. 8 Bortezomib 引起周邊神經病變事件之相關因子 49 5. 8. 1 周邊神經病變相關因子之單變項比例風險迴歸模式分析 49 5. 8. 2 周邊神經病變相關因子之多變項比例風險迴歸模式分析 52 5. 9 給藥途徑對於周邊神經病變風險的影響-模型校正 54 5. 9. 1 給藥途徑 54 5. 9. 2 次族群分析 54 5. 10 敏感度分析(sensitivity analysis) 57 5. 10. 1 更改研究族群定義 57 5. 10. 2 更改周邊神經病變定義 57 第 6 章 討論 61 6. 1 研究族群背景資料分析 61 6. 1. 1 研究族群背景資料分析 61 6. 1. 2 皮下注射與靜脈注射背景資料分析 62 6. 2 給藥相關資料分析 63 6. 2. 1 給藥相關資訊 63 6. 2. 2 化學治療療程分析 64 6. 3 Bortezomib相關副作用分析 64 6. 4 給藥途徑對於周邊神經病變風險影響 65 6. 5 給藥頻率對於周邊神經病變風險影響 68 6. 6 次族群分析(subgroup analysis) 69 6. 7 Bortezomib 引起周邊神經病變事件之相關因子 69 6. 8 敏感度分析 71 6. 9 研究限制與優勢 72 6. 9. 1 研究限制 72 6. 9. 2 研究優勢 72 第 7 章 結論與建議 73 參考文獻 74 附錄 80 | |
dc.language.iso | zh-TW | |
dc.title | 藥物治療多發性骨髓瘤病患引發周邊神經病變之危險因子分析 | zh_TW |
dc.title | Risk Factors of Treatment-related Peripheral Neuropathy in Patients with Multiple Myeloma | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃聖懿,田蕙芬,林芳如 | |
dc.subject.keyword | 周邊神經病變,bortezomib,皮下注射,危險因子,多發性骨髓瘤, | zh_TW |
dc.subject.keyword | Peripheral neuropathy,bortezomib,subcutaneous,risk factors,multiple myeloma, | en |
dc.relation.page | 89 | |
dc.identifier.doi | 10.6342/NTU201701185 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
顯示於系所單位: | 臨床藥學研究所 |
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