乳癌化學治療相關嚴重毒性反應預測性評分表之建立

除了零期的原位性乳癌，絕多數乳癌病人於手術後須佐以輔助性化療；而對於無法接受手術之轉移性乳癌病人，化學治療的臨床角色，更勝外科手術。化學治療常造成多項藥物不良反應，本研究希望歸納出容易誘發化療相關毒性反應的危險因子，並建立有效的預測機制，如此將有助於臨床工作者訂定適當的病人照顧計劃，達到最佳的醫療服務。係以回溯性研究方式，回顧曾接受化學治療之乳癌病人的病歷。完整收集各項資料，及病人發生十種化學治療相關毒性反應之情形，包括白血球總數、顆粒性白血球數量、血小板數目、血紅素值、感染（再細分為顆粒性白血球低下及正常兩種情況）、腸胃道的症狀（包括噁心或嘔吐，以及腹瀉）、黏膜炎，和失眠等。就病人所發生的化學治療相關不良反應，根據美國國家癌症學會所公佈之毒性反應參考準則（National Cancer Institute Common Terminology Criteria for Adverse Events v3.0, NCI-CTCAE）評估其嚴重程度。利用單變數分析方法，找出可能導致嚴重毒性反應的危險因子。然後，就具統計意義之危險因子，建立並驗證「預測發生化學治療相關毒性反應」的評分表。收案人數總計96名，化學治療之療程共188個。病人平均年齡，48.5±11歲；轉移性乳癌的比例，高達66%；乳癌的分類，以浸潤性管道內癌為主，佔94.8%；腫瘤荷爾蒙受器之表現，陽性者約佔50%；化學治療方式中，有或無使用anthracycline的療程，各佔一半。化學治療相關的毒性反應，達NCI-CTCAE第三級及以上者，總共232件，佔全部化療相關毒性反應之29.4%。而具生命威脅，甚至造成病人死亡之藥物不良反應事件，共計發生79件；其中，以顆粒性白血球減少症最常見，計有46件。本研究共找出6個具統計意義之危險因子，可能和發生嚴重化療相關毒性反應有關，即使用含有anthracycline的化學治療組合、化學治療開始前的身體質量指數低於22 kg/m2、血清麩氨草醋酸轉換酶（aspartate aminotransferase, AST）的基礎值大於35 u/L、化療前血紅素質小於12 mg/dL、化療前腎功能Clcr < 55 ml/min，以及化療前或期間有交錯進行放射線治療等。依據6個具統計意義之危險因子，所建立的預測嚴重化療毒性反應評分表，其靈敏度、特異度，及整體正確率，分別為74.7%、63.3%，及70.3%。針對需要接受化學治療的乳癌病人，所建立之預測嚴重化療相關毒性反應的評分表，可以提供臨床醫師作為照顧乳癌病人的參考。但基於資料的收集不易，確實可能影響研究的結果與品質。故關於本評分表之信度、效度，及實用性，未來仍需規劃相關研究，作進一步的驗證。

關鍵字

乳癌；化學治療；藥物不良事件；嚴重毒性反應；危險因子

並列摘要

Most breast cancer patients must be treated with adjuvant chemotherapy after surgery except those with carcinoma in situ. For the patients of metastatic breast cancer, the successful rate of chemotherapy was higher than that of surgery. The goal of present study was to identify the risk factors of chemotherapy-induced toxicities and to establish efficient forecast mechanisms to formulate applicable care plans for patients. The study retrospectively collected the data of chemotherapy-induced toxicities by reviewing the medical charts of those patients with breast cancer received chemotherapy. The univariate analysis was performed to identify the risk factors. The statistically significant risk factors were selected to construct a scale to predict the occurrence of chemotherapy-related toxicity. The study included 96 patients underwent 188 courses of chemotherapy. The average age of the patients was 48.5+11 years old. The percent of subjects with metastatic breast cancer was as high as 66%. Infiltrating ductal carcinoma, with a rate of 94.8%, happened to be the majority of breast cancers. Positive results from tumorous hormone receptor occurred in 50% of the patients. Among all the chemotherapies, treatment with or without using anthracycline occurred in half of the patients. In a total of 787 chemotherapy-related adverse events, 232 (29.4%) reached level three or above in National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. There were 79 life-threatening or death associated adverse drug events, and 46 cases of them were neutropenia. Six risk factors have been found to be statistically significant in this study, including body mass index lower than 22 kg/m2 before chemotherapy, the polychemotherapy involving anthracycline, the renal function Clcr less than 55 ml/min before chemotherapy, baseline value of AST (aspartate aminotransaminase) greater than 35 u/L, baseline value of hemoglobin lower than 12 mg/dl, and radiotherapy before chemotherapy. The scale to predict serious chemotherapy-related toxicity was constructed by using the six risk factors, resulting in a sensitivity of 74.7%, specificity of 63.3%, and total accuracy of 70.3%. Careful monitoring of chemotherapy related adverse reactions were required with patients with high risk scores. Further studies will warrant verifying the reliability, validity, and usefulness of this scale.

並列關鍵字

breast cancer ； chemotherapy ； adverse drug events ； severe toxicities ； risk factor

參考文獻

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乳癌化學治療相關嚴重毒性反應預測性評分表之建立

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