台大醫院非小細胞肺癌病患使用Docetaxel (Taxotere)每週給藥作為後線化學治療之迴溯性分析研究

Retrospective Study of Weekly Docetaxel (Taxotere) in Previously Treated Non-Small Cell Lung Cancer

羅英(Yin Lo)

指導教授 ： 楊志新

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.00789

摘要

肺癌為最常見之惡性疾病之一，亦為惡性腫瘤中死亡率最高者之一，在國人癌症死因中高居第二位。自從發現含鉑化學治療對於非小細胞肺癌有益，在嚴重非小細胞肺癌病患中，化學治療的使用也日益廣泛，也使得需要後線化療之病患日漸增加。
Docetaxel為一紫杉醇類似物，對於非小細胞肺癌單獨使用亦有活性，為美國藥物食品管理局第一個核准使用於非小細胞肺癌第二線化學治療的藥物。然而，傳統的docetaxel 給藥方式，常造成釵h嚴重的急性副作用；一些小型的研究發現，若以低劑量每週給藥，可減低急性毒性，而一些累積毒性則開始較為顯著。
為回顧docetaxel每週給藥作為非小細胞肺癌後線化療之使用，以及分析發生毒性之危險因子，本研究中以回溯性分析方式，收集臺大醫院使用docetaxel每週單獨給藥作為後線治療之非小細胞肺癌病患進行分析，總共有155名病患被納入分析。分析結果發現，發生嚴重白血球降低或低嗜中性球之危險因子包括初始劑量、前次化學治療發生白血球低下、給藥前白血球數四千以下、慢性病毒性肝炎感染、以及年齡七十歲以上；血中ALT偏高則增加需治療之體液滯留症狀之危險，而較高血中白蛋白濃度、曾手術切除腫瘤、靜脈注射類固醇輔助治療則減低其危險。給藥前白血球數一萬以上、以及較高的cisplatin累積劑量則增加中度至重度倦怠之危險性，而較長的docetaxel輸注時間以及曾手術切除腫瘤則降低之。之前曾使用anthracycline類藥物，以及慢性病毒性肝炎感染為因副作用而停藥之危險因子；治療前白血球數過多、較高的gemcitabine累積劑量為因治療不良反應死亡之危險因子。

關鍵字

副作用 ； 肺癌 ； 歐洲紫杉醇 ； 紫杉醇 ； 化學治療 ； 毒性

並列摘要

Lung cancer is one of the most frequently diagnosed malignant diseases, and one of those that lead to the most cancer related deaths. Ever since the beneficial effect of cisplatin-based chemotherapy was demonstrated in patients of non-small cell lung cancer, chemotherapy has been widely used for advanced NSCLC. With the widespread use of chemotherapy, patients requiring second line chemotherapy have increased. Docetaxel (Taxotere®, Aventis Pharma ) is a taxane derivative with single-agent activity against NSCLC; it is the first agent approved by the FDA for second-line chemotherapy of NSCLC. However, conventional dosing of docetaxel is associated with a high incidence of acute toxicity; results from several studies have suggested that weekly low-dose administration of docetaxel reduced acute toxicity, with cumulative toxicities becoming apparent.
This retrospective study was conducted to review the use of weekly docetaxel for NSCLC in a single tertiary medical center, and to identify risk factors for selected toxicity events. A total of 155 patients with previously treated NSCLC undertaking weekly docetaxel monotherapy for were included into analysis. Related risk factors were identified: severe leukopenia or neutropenia were predicted by initial dose, leukopenia in previous chemotherapy, low baseline leukocyte counts, chronic HBV or HCV infection, and age above 70 years. Elevated ALT levels increased the risk of fluid retention that requires treatment, while previous surgery, intravenous steroids, and increase of albumin levels decreased the risk. Increased cisplatin cumulative dose and baseline leukocytosis increased the risk of moderate to severe asthenia, while longer infusion time and previous surgery decreased the risk. Chronic HBV or HCV infection and previous chemotherapy with anthracyclines are predictive of treatment withdrawal due to any adverse event; baseline leukocytosis and higher gemcitabine cumulative dose were predictive of treatment-related death.

並列關鍵字

adverse event ； Taxotere ； lung cancer ； docetxel ； chemotherapy ； toxicity ； taxane

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