临床肿瘤学杂志
臨床腫瘤學雜誌
림상종류학잡지
CHINESE CLINICAL ONCOLOGY
2014年
6期
516-523
,共8页
秦锐%石燕%陈丽%吴志勇%韩雅琳%戴广海
秦銳%石燕%陳麗%吳誌勇%韓雅琳%戴廣海
진예%석연%진려%오지용%한아림%대엄해
西妥昔单抗%转移性结直肠癌%靶向治疗%联合化疗
西妥昔單抗%轉移性結直腸癌%靶嚮治療%聯閤化療
서타석단항%전이성결직장암%파향치료%연합화료
Cetuximab%Colorectal cancer with metastasis%Targeted therapy%Combined chemotherapy
目的：观察西妥昔单抗联合化疗治疗K-Ras野生型转移性结直肠癌的疗效及安全性，探讨可能影响疗效及预后的因素。方法收集2007年5月至2012年5月解放军总医院收治的K-Ras野生型转移性结直肠癌患者共90例，采用西妥昔单抗（400mg/m2，静滴，第1周，维持剂量每周250mg/m2或每2周500mg/m2）联合化疗方案，主要为含伊立替康为基础方案（ FOLFIRI或XELIRI或单药CPT-11）、含奥沙利铂为基础方案（ FOLFOX或XELOX）、5-FU/LV方案或单药卡培他滨。回顾性评估西妥昔单抗联合化疗在治疗中的疗效和安全性，分析患者临床病理特征，并探讨影响疗效的因素以及此类患者预后相关的因素。结果西妥昔单抗中位治疗时间为16周（6～44周），客观缓解率（ ORR ）为45?6％，疾病控制率（ DCR ）为87?8％。其中一线治疗ORR为51?6％，二线治疗ORR为40?0％，三线治疗ORR为18?2％。单因素分析显示，年龄、原发灶部位、西妥昔单抗治疗时间与疗效有关，差异具有统计学意义（ P＜0?05）。90例患者中位随访时间为20?2个月，82例（91?1％）复发转移，60例（66?7％）死亡。患者中位无疾病进展时间（PFS）为7?8个月，中位总生存时间（OS）为22?5个月。其中一线中位PFS为9?1个月，中位OS为27?6个月；二线中位PFS为7?7个月，中位OS为14?5个月；三线中位PFS为2?9个月，中位OS为6?7个月。单因素分析显示：原发灶部位、早期肿瘤缓解者以及西妥昔单抗治疗时间与PFS有关；原发灶部位、早期肿瘤缓解者、西妥昔单抗治疗时间以及转移侵及范围与OS有关。 Cox多因素生存分析显示：原发肿瘤病灶部位、早期肿瘤缓解是PFS的独立预后因素，转移侵及范围是 OS 的独立预后因素。西妥昔单抗相关治疗最常见的不良反应是痤疮样皮疹（78?0％），化疗相关的不良反应主要为腹泻、恶心呕吐、骨髓抑制，经对症处理后，患者均可耐受。结论西妥昔单抗联合多种方案化疗治疗晚期转移性结直肠癌患者，各线治疗均能取得较好的疗效，不良反应可耐受；原发灶部位可能是西妥昔单抗联合化疗的疗效预测因素，其与患者预后生存可能相关；早期肿瘤缓解可作为判断患者预后相关指标。
目的：觀察西妥昔單抗聯閤化療治療K-Ras野生型轉移性結直腸癌的療效及安全性，探討可能影響療效及預後的因素。方法收集2007年5月至2012年5月解放軍總醫院收治的K-Ras野生型轉移性結直腸癌患者共90例，採用西妥昔單抗（400mg/m2，靜滴，第1週，維持劑量每週250mg/m2或每2週500mg/m2）聯閤化療方案，主要為含伊立替康為基礎方案（ FOLFIRI或XELIRI或單藥CPT-11）、含奧沙利鉑為基礎方案（ FOLFOX或XELOX）、5-FU/LV方案或單藥卡培他濱。迴顧性評估西妥昔單抗聯閤化療在治療中的療效和安全性，分析患者臨床病理特徵，併探討影響療效的因素以及此類患者預後相關的因素。結果西妥昔單抗中位治療時間為16週（6～44週），客觀緩解率（ ORR ）為45?6％，疾病控製率（ DCR ）為87?8％。其中一線治療ORR為51?6％，二線治療ORR為40?0％，三線治療ORR為18?2％。單因素分析顯示，年齡、原髮竈部位、西妥昔單抗治療時間與療效有關，差異具有統計學意義（ P＜0?05）。90例患者中位隨訪時間為20?2箇月，82例（91?1％）複髮轉移，60例（66?7％）死亡。患者中位無疾病進展時間（PFS）為7?8箇月，中位總生存時間（OS）為22?5箇月。其中一線中位PFS為9?1箇月，中位OS為27?6箇月；二線中位PFS為7?7箇月，中位OS為14?5箇月；三線中位PFS為2?9箇月，中位OS為6?7箇月。單因素分析顯示：原髮竈部位、早期腫瘤緩解者以及西妥昔單抗治療時間與PFS有關；原髮竈部位、早期腫瘤緩解者、西妥昔單抗治療時間以及轉移侵及範圍與OS有關。 Cox多因素生存分析顯示：原髮腫瘤病竈部位、早期腫瘤緩解是PFS的獨立預後因素，轉移侵及範圍是 OS 的獨立預後因素。西妥昔單抗相關治療最常見的不良反應是痤瘡樣皮疹（78?0％），化療相關的不良反應主要為腹瀉、噁心嘔吐、骨髓抑製，經對癥處理後，患者均可耐受。結論西妥昔單抗聯閤多種方案化療治療晚期轉移性結直腸癌患者，各線治療均能取得較好的療效，不良反應可耐受；原髮竈部位可能是西妥昔單抗聯閤化療的療效預測因素，其與患者預後生存可能相關；早期腫瘤緩解可作為判斷患者預後相關指標。
목적：관찰서타석단항연합화료치료K-Ras야생형전이성결직장암적료효급안전성，탐토가능영향료효급예후적인소。방법수집2007년5월지2012년5월해방군총의원수치적K-Ras야생형전이성결직장암환자공90례，채용서타석단항（400mg/m2，정적，제1주，유지제량매주250mg/m2혹매2주500mg/m2）연합화료방안，주요위함이립체강위기출방안（ FOLFIRI혹XELIRI혹단약CPT-11）、함오사리박위기출방안（ FOLFOX혹XELOX）、5-FU/LV방안혹단약잡배타빈。회고성평고서타석단항연합화료재치료중적료효화안전성，분석환자림상병리특정，병탐토영향료효적인소이급차류환자예후상관적인소。결과서타석단항중위치료시간위16주（6～44주），객관완해솔（ ORR ）위45?6％，질병공제솔（ DCR ）위87?8％。기중일선치료ORR위51?6％，이선치료ORR위40?0％，삼선치료ORR위18?2％。단인소분석현시，년령、원발조부위、서타석단항치료시간여료효유관，차이구유통계학의의（ P＜0?05）。90례환자중위수방시간위20?2개월，82례（91?1％）복발전이，60례（66?7％）사망。환자중위무질병진전시간（PFS）위7?8개월，중위총생존시간（OS）위22?5개월。기중일선중위PFS위9?1개월，중위OS위27?6개월；이선중위PFS위7?7개월，중위OS위14?5개월；삼선중위PFS위2?9개월，중위OS위6?7개월。단인소분석현시：원발조부위、조기종류완해자이급서타석단항치료시간여PFS유관；원발조부위、조기종류완해자、서타석단항치료시간이급전이침급범위여OS유관。 Cox다인소생존분석현시：원발종류병조부위、조기종류완해시PFS적독립예후인소，전이침급범위시 OS 적독립예후인소。서타석단항상관치료최상견적불량반응시좌창양피진（78?0％），화료상관적불량반응주요위복사、악심구토、골수억제，경대증처리후，환자균가내수。결론서타석단항연합다충방안화료치료만기전이성결직장암환자，각선치료균능취득교호적료효，불량반응가내수；원발조부위가능시서타석단항연합화료적료효예측인소，기여환자예후생존가능상관；조기종류완해가작위판단환자예후상관지표。
Objective To investigate the efficacy and safety of the cetuximab combined with chemotherapy for patients with metastasis from colorectal cancer whose K-Ras status were wild type and explore the factors that may affect the efficacy and prognosis. Methods Retrospectively collected the clinical data of 90 patients with metastasis from colorectal cancer whose K-Ras status were wild type. Cetuximab 400mg/m2 was intravenously given at first dose and maintenance at 250mg/m2 every week or 500mg/m2 every two weeks. Combined chemotherapy regimen included, irinotecan-based chemotherapy(FOLFIRI or XELIRI or irinotecan monotherapy), oxaliplatin-based chemotherapy( FOLFOX or XELOX) ,other regimens, such as 5-FU/leucovorin or capecitabine monotherapy. The ef-ficacy and safety of each line of chemotherapy was summarized and assessed, and the relationship between clinicopathology features, treatment characteristics and efficacy, explore the factors associated with prognosis were analyzed retrospectively. Results The median duration treatment of cetuximab was 16 weeks( 6-44 weeks) . And in all patients the objective response rate( ORR) was 45?6%,and the disease control rate( DCR) was 87?8%. The DCR in first line treatment was 51?6% better than in second line, whose was 40?0%, and the DCR in third line was 18?2%. The age, location of primary tumor, treatment time of cetuximab might affect the efficacy fo cetux- imab plus chemotherapy. In the 90 patients, recurrent metastases were occurred in 82 cases( 91?1%) and death in 60 cases( 66?7%) . The median PFS( mPFS) was 7?8 months and median OS( mOS) was 22?5 months. In the first line treatment of cetuximab plus chemo-therapy, mPFS was 9?1 months and mOS was 27?6 months. In second line treatment mPFS was 7?7 months and mOS was 14?5 month. in third line mPFS was 2?9 months and mOS was 6?7 months. Univariate survival analysis showed that the location of primary tumor, early tumor response and treatment time of cetuximab were related to PFS and OS of the patients, and the metastasis scope was related to the OS of patients. Using the Cox multivariate hazards model to analysis the clinicopathological factors, which showed that the loca-tion of primary tumor and early tumor response were the independent risk factors affecting the PFS of patients, the metastasis scope was the independent risk factor affecting the OS of patients. The most common adverse reaction related to cetuximab is acne-like rash, the side effects associated with chemotherapy mainly were diarrhea, nausea, vomiting, bone marrow suppression. After symptomatic treat-ment, patients can tolerate. Conclusion Cetuximab combined chemotherapy in each line treatment of patients with metastases from colorectal cancer can get great efficacy, and the adverse reactions can be tolerated. The location of primary tumor might be the predic-tors of the efficacy, and it is also associated with the prognosis of the patients. As ETS Shows that early tumor response could be one of the outcome indicators of mCRC.
