- 學位論文
乳癌病患化學治療引發白血球低下之評估
Evaluation of Leukopenia Induced by Chemotherapy in Breast Cancer Patients
摘要
研究背景 骨髓抑制(myelosuppression)是化學治療中常見的副作用，其對血液系統之影響非常廣泛，其中尤以嗜中性白血球低下症(neutropenia)最常見，其引發之後遺症包括有：感染危險率增加、產生發熱性嗜中性白血球低下症(febrile neutropenia or neutropenic fever，FN)、導致住院或住院時間延長、病患生活品質下降，除此之外，也常因白血球數目降低，而必須延後化學治療之時間點或是降低化學治療之劑量，因嗜中性白血球低下症所造成之後遺症，不僅增加了醫療成本，也對化學治療的療效果產生影響。本次研究目的便是確立出乳癌病患接受化療後產生嚴重程度白血球低下症之危險因子，進而建立出一個用以估算化療後白血球數目之預測模式，期望本次研究之結果能提供臨床工作者一個參考資訊，藉以提早預防乳癌病患產生嚴重白血球低下症之情形。 方法 收納民國90年1月至95年12月間於高雄醫學大學附設中和紀念醫院接受化學治療之乳癌病患予以納入本研究，經由回顧病歷取得相關資料，以卡方檢定(chi-square test)檢驗出何者為嚴重程度白血球低下症之危險因子，而以複迴歸(multiple regression)建立一套預測模式來估算化學治療後之白血球數目。 結果 總共有375個個案被納入本研究，不同的化學治療療程(p-value < 0.0001，??2 = 87.05)及雌激素接受體狀態與嚴重程度之白血球低下症發生率達到統計上之顯著差異(p-value = 0.0471，??2 =5.27)。在化學治療後白血球數目之預測模式部份，治療前白血球之數目每增加1 × 103/mm3，則對應於接受完化學治療後之白血球數目將增加0.16 × 103/mm3，p值＜0.0001；年齡在40歲以上而未滿50歲之病人也較未滿30歲之組別在化學治療後之白血球數目多出0.36 × 103/mm3，p值＜0.0001；在各個化學治療療程的情形為，接受docetaxel、epirubicin及cyclophosphamide(TEC)治療的組別比起接受fluorouracil、epirubicin及cyclophosphamide(FEC)療程的病人在化學治療後之白血球數目減少0.59 × 103/mm3 (p值＜0.0001)，而給予fluorouracil、 epirubicin、 cyclophosphamide ，之後再接續給予paclitaxel(FEC+T*)此療程的個案比起FEC療程在化學治療後之白血球數目則會增加1.99 × 103/mm3 (p值＜0.0001) ；有給予G-CSF介入治療的病患在化學治療後白血球數目比起沒有接受G-CSF治療的病人，會減少0.46 × 103/mm3，p值＜0.0001。 結論 易導致嚴重白血球低下症之危險因子為化學治療療程不同及雌激素接受體之狀態，在化學治療後白血球數目預測模式部分，化療前白血球數目越高者，其餘化學治療後之白血球數目亦會較高；而年齡介於40歲以上(包含40歲)、50歲以下之病患其對其化學治療後之白血球數目是有保護作用的；在化學療程部份，接受TEC及FEC+T*之病患對其白血球數目會有所影響；而有G-CSF介入治療之個案族群，在化學治療後之白血球數目反而是降低的
並列摘要
Introduction Myelosuppression (MS) is a major side effect of chemotherapy, and it is associated with an increased risk of infection, impaired quality of life and prolonged hospitalization. Chemotherapy dose reductions and delays are common sequelae and may affect treatment outcomes. We want to identify risk factors about leukopenia after total chemotherapy cycles and to develop a model used to predict the relationship between patient characteristics and leukocyte counts among the different common chemotherapy regimens in hospital. It may benefit us to provide a prophylactic measure such as granulocyte colony-stimulating factor (G-CSF). Therefore we can prevent serious consequences of leukopenia. Methods Patients who were diagnosed as breast cancer and had received chemotherapy regimens such as FEC, TEC, FLC, FEC plus T* or TE (F, fluorouracil; E, epirubicin; C, cyclophosphamide; T, docetaxel; L, doxorubicin; T*, paclitaxel) between 2001 and 2006 in C.-H. Memorial Hospital, KMU were included in the study retrospectively. We identified the risk factors and developed a model by chi-square test and multiple regression. Results 375 patients were eligible for this study. The severe leukopenia is statistically significantly associated with chemotherapy regimens (??2 = 87.05, p-value < 0.0001) and estrogen receptor status (??2 =5.27, p-value = 0.0471). A model is developed to predict leukocyte counts after total cycles of chemotherapy, four independent variables were identified in the multiple regression: (1) age between 40 and 49 years old at diagnosis (β = 0.36, p-value < 0.0001) (2) baseline leukocyte counts (β = 0.16, p-value < 0.0001) (3) different chemotherapy regimens (TEC, β =-0.59, p-value < 0.0001, FEC+T*, β =1.99, p-value < 0.0001) and (4) G-CSF use or not (β =-0.46, p-value < 0.0001). Conclusions The risk factors of leukopenia are different chemotherapy regimen and estrogen receptor status. Leukocyte counts after total cycles by chemotherapy of breast cancer can be affected by baseline leukocyte counts, different chemotherapy regimens, age at diagnosis and G-CSF use or not.