分析病人使用含oxaliplatin的化療處方後引起的過敏反應及預防性給予抗組織胺藥品的療效評估

Analyzing the Allergic Reactions Induced by the Chemotherapy Regimens Including Oxaliplatin and Evaluating the Effectiveness of Receiving Preventive Antihistamine Drugs

吳佳璇(Jia-Syuan Wu)

指導教授 ： 柯黃盛

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00124

摘要

【研究背景】
根據衛生福利部國民健康署最新公告的99年癌症登記報告，胃癌發生率在男性排名第6位，在女性排名第8位；結腸、直腸癌發生率在男性排名第1位，在女性排名第2位。Oxaliplatin目前為治療結腸、直腸癌和晚期胃癌主要的化學治療藥物之一。Oxaliplatin為第三代白金類的化學藥物，目前健保局核准的適應症為第三期結腸癌、轉移性直腸結腸癌及局部晚期或轉移性胃癌的治療。根據許多的研究報告指出，接受oxaliplatin治療的病人約有90%會引起周邊神經病變，其神經毒性的發生與劑量相關，大部分病人可在療程中自行復原，因此臨床的醫療人員都能衛教病人有關神經毒性的不良反應。但近幾年通報oxaliplatin的不良反應除了神經毒性之外，過敏反應也有逐漸增加的趨勢。嚴重的過敏反應甚至導致部分病人因為無法耐受而中斷oxaliplatin的治療。
【研究目的】
臨床治療上，當病人因為oxaliplatin引起過敏反應時，會給予抗組織胺藥品來緩解，大部分病人的過敏症狀可以在給予抗組織胺藥品後達到症狀減緩或症狀消除的結果。由於抗組織胺藥品確實可以達到緩解病人因為施打oxaliplatin引起過敏反應的效果，所以臨床上有部分醫師會在病人施打oxaliplatin之前事先給予抗組織胺藥品來預防過敏反應的發生。但是抗組織胺藥品常會引起病人暈眩、噁心或影響意識狀態的副作用；另外在臨床上也觀察到部分病人事先施打抗組織胺藥品並無法有效預防oxaliplatin引起的過敏反應。本篇研究旨在探討施打oxaliplatin之前，事先給予抗組織胺藥品對於預防oxaliplatin引起過敏反應的療效。由於目前尚無預防oxaliplatin引起過敏反應的相關治療指引，因此希望藉此研究的結果能提供臨床醫療處置及照護的參考。
【研究方法】
研究設計採病例回溯性對照研究（case-control study）。研究對象為南部某醫學中心2008年1月至2013年5月施打oxaliplatin產生過敏反應的病人。研究樣本分成兩組，病例組為施打oxaliplatin前事先沒有給予抗組織胺藥品的病人；對照組為施打oxaliplatin前有事先給予抗組織胺藥品的病人。藉由病歷回溯的方式，合併院內藥物不良反應通報系統來分析病人施打oxaliplatin後所引起的過敏反應發生率及過敏嚴重程度。統計工具使用SPSS 19.0 for windows 套裝軟體進行分析，統計方法以百分比、平均數、中位數及標準差等進行描述性統計，及以Chi-Square、95%信賴區間等分析方法進行推論性統計。
【研究結果】
在2008年1月至2013年5月共有545位病人接受oxaliplatin的施打，納入分析的病人共535位，其中有85位(15.6%)通報過敏反應。這85位病人平均在接受第八次oxaliplatin施打時產生過敏。有61位病人接受oxaliplatin re-challenge，再度產生過敏反應的有46位 (75.4%)。有24位病人 (28.2%) 因此中斷oxaliplatin的治療。Oxaliplatin引起的過敏反應症狀大部分以皮膚搔癢為主 (76.5%)，其次為呼吸喘、胸悶 (32.3%)，另外有盜汗、嘔吐等症狀。
將這535位有施打oxaliplatin的病人分成兩組，病例組為施打oxaliplatin前沒有事先給予抗組織胺藥品的病人共164人，其中有27位病人(16.46%)產生過敏反應；對照組為施打oxaliplatin前事先有給予抗組織胺藥品的病人共371人，其中有58位病人(15.63%)產生過敏反應。兩組病人產生過敏反應的比率在統計上並沒有顯著的差異(P>0.05)，顯示在施打oxaliplatin之前事先給予抗組織胺的藥品並不能有效預防過敏反應的發生。
【結論】
研究發現病例組於施打oxaliplatin前沒有事先給予抗組織胺藥品比起對照組於施打oxaliplatin前有事先給予抗組織胺藥品在過敏反應的發生率，於統計上無顯著之差異。而臨床上觀察到事先給予抗組織胺藥品不但會增加病人暈眩、噁心、影響意識狀態的副作用，且無法有效預防oxaliplatin引起的過敏反應。
此研究結果可提供臨床醫療上之參考，當病人因oxaliplatin產生過敏反應時，再給予抗組織胺藥品取代事先給予抗組織胺藥品，不但能降低病人施打抗組織胺藥品的不良反應，也能減少臨床執行業務的複雜程度，在整體的醫療層面更能增加成本效益。
臨床上衛教病人除了常見的腸胃道副作用及神經毒性，也要加強
病人對於過敏反應的認知及自我照護的能力。尤其當病人曾經發生對oxaliplatin過敏的症狀時，之後再接受oxaliplatin rechallenge(再次挑戰)仍有高達70%以上的病人會再次產生過敏反應。而其他預防性的處置，例如延長oxaliplatin的輸注時間或降低oxaliplatin的施打劑量是否能降低oxaliplatin引起的過敏反應則需要更多研究來證實。

關鍵字

Oxaliplatin ； 過敏 ； 抗組織胺 ； 預防

並列摘要

【Background】
According to the latest 2011 cancer registration report announced by Taiwan Health Promotion Administration, Ministry of Health and Welfare, the incidence of gastric cancer is ranked No. 6 in males and No. 8 in females, while the incidence of colorectal cancer ranked No. 1 in males and ranked No. 2 in females. Oxaliplatin is currently one of the main drugs of chemotherapy for colorectal cancer and end-stage gastric cancer. Oxaliplatin is a third- generation platinum compound, which is approved by the National Health Insurance Bureau for treatment of stage III colon-rectal cancer, metastatic colorectal cancer and partially end-stage or metastatic gastric cancer. According to many studies, about 90% of the patients who have received oxaliplatin treatments are accompanied by peripheral neuropathy, whose grade is related to the dosage of oxaliplatin. Most of these adverse events can recover during the chemotherapy cycles. The clinical medical staff can provide patients with instructions to against these adverse drug reactions. However, registered allergic reactions as another adverse drug reaction of oxaliplatin, besides neuropathy, are increasing in recent years, severe allergic reactions even interrupted ongoing oxaliplatin treatments because some of the patients came to the end of endurance.
Objective :
During the clinical treatment, patients are given antihistamine drugs to alleviate allergic reactions induced by oxaliplatin, and it is successful in most of them. Due to the effect, some clinical doctors give the patients antihistamine drugs in advance to prevent allergic reactions before the patients receive oxaliplatin infusions. However, on the one side, antihistamine drugs often cause dizziness, nausea, or conscious disturbance. On the other side, the antihistamine drugs cannot prevent some patients effectively from oxaliplatin-induced allergic reactions by clinical observation.
Because there is no relevant guideline for the prevention from oxaliplatin-induced allergic reactions, this study aims to evaluate the effectiveness of the prevention of antihistamine drugs against oxaliplatin-induced allergic reactions in order to provide information on clinical treatment and post-treatment care.
【Methods】
This is a retrospective case-control study with subjects composed of patients who have allergic reactions after receiving oxaliplatin infusions from January 2008 to May 2013 in a medical center in southern Taiwan. The subjects are divided into two groups: the study group consisted of patients without taking antihistamine drugs before the oxaliplatin infusion; the control group consisted of patients taking antihistamine drugs before the oxaliplatin infusions. By means of case review and combining with the adverse drug reaction registration system in the hospital, we analyze the incidence of oxaliplatin-induced allergic reactions and the grade of allergic reactions. The data are processed and analyzed by SPSS 19.0 for Windows and explained with descriptive statistics of percentage, mean value, median value and standard deviation, as well as inferential statistics of Chi-Square test and 95% confidence interval analysis.
【Results】
There were 545 patients receiving oxaliplatin infusions from January 2008 to May 2013. Finally 535 patients are included for analysis, including 85 patients (15.6%) reported with allergic reactions, which occurred after a median of the eighth infusion of oxaliplatin. 61 patients of them received oxaliplatin re-challenge; 46 of these 61 patients (75.4%) led to further reactions, and 24 patients (28.2%) stopped their oxaliplatin treatment owing to intolerance to oxaliplatin-induced allergic reactions. The symptoms of oxaliplatin-induced allergic reactions are primarily skin rashes (76.5%), secondly shortness of breath and chest tightness (32.3%), sweating, vomiting and so on. These 535 patients receiving oxaliplatin infusions were divided into two groups, 164 patients without receiving antihistamine drugs before the oxaliplatin infusion in the study group, and 371 patients receiving antihistamine drugs before the oxaliplatin infusion in the control group. 27 patients (16.46%) in the study group had allergic reactions, while allergic reactions happened to 58 patients (15.22%) in the control group. The rates of oxaliplatin-induced allergic reactions show no statistically significant difference (P> 0.05) between the two groups, revealing that receiving antihistamine drugs before the oxaliplatin infusion cannot effectively prevent allergic reactions.
【Conclusion】
This study reveals that the effectiveness of giving patients in the study group antihistamine drugs to prevent allergic reactions caused by oxaliplatin had no statistically significant difference from that in the control group. It was also found that giving antihistamine drugs in advance not only increases side effects such as dizziness, nausea and conscious disturbance but also could not effectively prevent allergic reactions caused by oxaliplatin.
The findings provide information for clinical treatments that giving antihistamine drugs after allergic reactions occur due to oxaliplatin instead of giving it in advance for prevention not only reduces the complexity of the clinical implementation and adverse reactions caused by antihistamine drugs but also helps increase cost-effectiveness in all the aspects of medical treatment.
Clinically, patient instructions about patient’s awareness of allergic reactions and self-care abilities, besides the often seen gastrointestinal side effects and neuropathy, should be enhanced, especially for the patients who have had allergic symptoms due to oxaliplatin and to more than 70% of whom it happens again after oxaliplatin re-challenge. Other preventive methods such as extending the time of oxaliplatin infusions or decreasing oxaliplatin dosage to reduce allergic reactions need more researches to verify their effectiveness.

並列關鍵字

Oxaliplatin ； allergic reaction ； anti-histamine ； prevention

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