诱导化疗加同步放化疗治疗ⅢB期肺鳞癌的临床效果

2014-12-15 03:20王希龙
中国当代医药 2014年33期
关键词:同步放化疗紫杉醇顺铂

王希龙

[摘要] 目的 评价TP(紫杉醇+顺铂)方案诱导化疗后加EP(依托泊苷+顺铂)方案同步放化疗在ⅢB期肺鳞状细胞癌治疗中的效果和毒性反应。 方法 回顾性分析2010年7月~2013年6月本院64例不能手术的初治ⅢB期肺鳞癌患者,采用诱导化疗加同步放化疗。放疗采用适形放疗,给予总剂量为60~66 Gy/30~33次/6~7周。诱导化疗给予2周期TP方案化疗,具体为:紫杉醇150 mg/m2,第1天,顺铂25 mg/(m2·d),第2~4天,21 d为1个周期。同步放化疗采用EP方案化疗,在放疗开始的第1、8、29、36天给予顺铂50 mg/(m2·d),第1~5、29-33天给予依托泊苷50 mg/(m2·d),放疗期间共完成2个周期化疗。放疗结束后1个月进行疗效评价。 结果 完全缓解(CR)11例(17.2%)、部分缓解(PR)49例(76.6%),总有效率为93.8%。骨髓抑制、放射性食管炎、胃肠道反应均为Ⅰ~Ⅲ度,经对症处理后均恢复正常。 结论 患者能耐受诱导化疗加同步放化疗不良反应,安全可行,可明显提高ⅢB期肺鳞癌的疗效。

[关键词] 诱导化疗;同步放化疗;紫杉醇;顺铂;依托泊苷;肺鳞状细胞癌

[中图分类号] R734.2 [文献标识码] B [文章编号] 1674-4721(2014)11(c)-0152-03

[Abstract] Objective To evaluate the efficacy and toxicity of TP (Paclitaxel+Cis-platinum) project inducing chemotherapy and EP (Etoposide+Cis-platinum) project concurrent radiochemotherapy in the treatment of ⅢB phase squamonus cell carcinoma of lung. Methods 64 cases of patients with lung ⅢB phase squamonus cell carcinoma treated in our hospital from July 2010 to June 2013 were retrospectively analyzed,induction chemotherapy plus concurrent radiochemotherapy was used.Conformal radiotherapy was used,were taken with a total dose of 60-66 Gy/30-33 times/6-7 weeks.Inducing chemotherapy which was given with TP project chemotherapy for 2 weeks: Paclitaxel 150 mg/m2 d1,Cis-platinum 25 mg/(m2·d) d2-4,a period was 21 days.The concurrent chemoradiotherapy was taken with EP chemotherapy project,at the beginning of radiotherapy in d1,d8,d29,d36 were given with Cis-platinum 50 mg/(m2·d);d1-5,d29-33 were given with etoposide 50 mg/(m2·d),2 phase of chemotherapy during radiotherapy were done. Results The efficacy was evaluated after 1 month radiotherapy.There were 11 cases (17.2%) of complete remission (CR),49 cases (76.6%) of partial remission (PR),the total effective rate was 93.8%.Bone marrow suppression,radioactive esophagitis,gastrointestinal reaction were all Ⅰ to Ⅲ degree,and returned to normal after symptomatic treatment. Conclusion Patients can be tolerate the adverse reaction of induction chemotherapy plus concurrent chemoradiotherapy,it is safe and feasible,which can obviously improve the curative effect of lung ⅢB phase squamonus cell carcinoma.

[Key words] Induction chemotherapy;Concurrent radiochemotherapy;Paclitaxel;Cis-platinum;Etoposide;Squamous cell carcinoma of the lung

非小细胞肺癌(non-small cell lung carcinoma,NSCLC)约占肺癌的80%[1],肺鳞癌(squamous cell carcinoma,SCC)占NSCLC的30%~40%[2],大部分SCC起源于中心性主支气管、叶支气管或段支气管,大约3/4的SCC是中心型,初治时不能手术的ⅢB期患者占绝大多数。对于ⅢB期NSCLC,单纯常规放疗的5年生存率为4%~6%,三维适形放疗为19%[3-4]。近年多个多中心随机研究证实同步放化疗优于序贯放化疗[5-7],因此目前同步放化疗是局部晚期NSCLC标准治疗手段。但对于原发病灶及转移淋巴结较大的患者,放疗靶区过大,最终导致放疗计划难以实施,或因放疗中副反应大而被迫终止放疗的情况时有发生。本文回顾性分析不能手术的ⅢB期SCC经诱导化疗加同步放化疗的临床疗效及毒性反应。endprint

1 资料与方法

1.1 一般资料

纳入标准:①初治不能手术的ⅢB期SCC,椎体及心脏直接受侵者不纳入组。按UICC第七版标准并根据治疗前临床检查、胸腹部CT和头部磁共振、骨扫描结果进行分期。②经病理学证实。③血常规及肝肾功能正常。本院2010年7月~2013年6月共64例患者纳入研究,其中男55例,女9例;年龄(非正态分布)24~70岁,中位年龄58岁;70分≤KPS评分<90分12例,KPS评分≥90分52例。

1.2 治疗方法

1.2.1 放疗 胸部放疗开始于同步治疗的第1天,应用直线加速器的6MV-X线适形放疗。2 Gy/d,5次/周,总剂量60~66 Gy/30~33次/6~7周。放疗前行CT模拟定位并把定位图像传到靶区勾画系统,GTV为诱导化疗后影像学(包括CT、磁共振、PET-CT等)显示的原发肿瘤+转移淋巴结区域。如果化疗期间病变进展,GTV则应包括进展的病变范围。如果患者有阻塞性肺不张,应考虑将不张的部分置于GTV以外。磁共振和PET-CT均可作为排除不张的依据。经过3~4周的治疗,不张的肺可能已经张开,这时候应该重新进行定位、勾画靶区并重做计划。考虑纵隔淋巴结阳性的标准:①最短径>1 cm;②最短径≤1cm但同一部位肿大淋巴结>3个;③淋巴结内部有坏死、边缘有强化;④诱导化疗后淋巴结明显缩小。CTV应以化疗后的肺内病变范围为准,加上化疗前的受侵淋巴结区域,如果化疗后完全缓解,则应将化疗前的纵隔淋巴结受侵区及肺内病变的范围勾画为CTV,最少给予50 Gy。CTV为GTV外放6 mm。除非确有外侵存在,CTV不应超出解剖学边界。如果隆突下淋巴结或者纵隔淋巴结受侵,同侧肺门应包入CTV。对于右中下叶或者左舌叶、左下叶病变,如果纵隔淋巴结受侵,隆突下淋巴结应包入CTV。PTV为CTV加上肿瘤的运动范围,再加上7 mm的摆位误差。治疗中放疗20次复查颈胸部CT决定是否缩野、重做计划。

1.2.2 化疗 诱导化疗给予2周期TP方案化疗,具体为:紫杉醇(扬子江药业集团有限公司,批号H20053001)150 mg/m2,第1天,顺铂(齐鲁制药有限公司,批号H20 023461)25 mg/(m2·d),第2~4天,21 d为1个周期。同步放化疗采用EP方案化疗,具体为:放疗开始的第1、8、29、36天给予顺铂50 mg/(m2·d),第1~5、29~33天给予依托泊苷(齐鲁制药有限公司,批号H37023182)50 mg/(m2·d),放疗期间共完成2个周期化疗。化疗的辅助用药按常规进行。

1.3 疗效和毒性评估

应用统计学软件SPSS Statistics 17.0进行数据分析。治疗期间每周记录1次体检情况,测定1次血常规及肝、肾功能,放疗结束后1个月复查颈胸部CT进行疗效评价。采用实体瘤1.1版RECIST疗效评价标准。完全缓解(CR):所有目标病灶消失;部分缓解(PR):基线病灶长径总和缩小≥30%;进展(PD):基线病灶长径总和增加≥20%或出现新病灶;稳定(SD):基线病灶长径总和有缩小但未达PR或有增加但未达PD。总有效率=(CR+PR)例数/总例数×100%。毒性反应根据CTCAE 4.0版的标准进行评价,分为1~5级。1级:轻度,无症状或轻度症状;仅临床或诊断发现;无需治疗。2级:中度,最小的、局部的或非侵入性治疗指征;年龄相关工具性日常生活活动受限。3级:重度或重要医学意义,但不会立即危及生命;住院治疗或延长住院时间指征;致残;自理性日常生活活动受限。4级:危及生命,需紧急治疗。5级:死亡。

3 讨论

同步放化疗是不能手术切除的局部晚期NSCLC的常用治疗方法。已有许多临床研究显示同步放化疗可协同作用,提高局部控制率及远期生存率[8]。对一般状况好的患者,放化疗同时应用已成为标准的治疗方法。但对于放疗靶区较大的患者,放疗计划有时难以实施,因放疗副反应大导致放疗被迫停止或不能如期完成,因而造成疗效下降。诱导化疗如有效可降低瘤负荷,并可协助鉴别是否为转移淋巴结,从而使放疗靶区明显缩小,有利于放疗计划的实施及更好地保护正常组织。有报道显示[9],以GTV、CTV、PTV中位值155、302、484 cm3为界,随着靶体积的增大,放疗后Ⅱ级以上放射性肺炎发生率明显增加(P<0.05),放疗后1、3、5年生存率和中位生存期均呈下降趋势(χ2=5.16,P=0.023)。

曾有报道[10],泰素、卡铂诱导化疗加同步放化疗治疗ⅢA和ⅢB期NSCLC的研究资料显示,诱导化疗有效率为38%,放化疗总有效率为59%。据临床观察,应用紫杉醇注射液同步放化疗的口腔黏膜炎、放射性食管炎及放射性肺炎的发生率要明显高于EP方案,放疗后期患者不能耐受,甚至导致放疗中断、延长放疗时间。以上报道中的病例为NSCLC,而本研究治疗的病例均为SCC,本研究中近期疗效高于该文献报道,可能与放疗技术的进步、化疗方案的改进及病例的选择有关。宋启斌等[11]报道化疗与三维适形放疗同步治疗Ⅲ期NSCLC原发灶总有效率为91.7%,纵隔转移淋巴结总有效率为100%,SCC总有效率为94.7%,腺癌总有效率为80.0%。该研究未用诱导化疗,研究结果与本研究结果相似,可能与本研究的病例期别偏晚有关,至于远期疗效及晚期并发症有待进一步随访。

[参考文献]

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[2] 孙燕,石远凯.临床肿瘤内科手册[M].北京:人民卫生出版社,2008:391.

[3] Perez CA,Pajak TF,Rubin P,et al.Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy.Report by the Radiation Therapy Oncology Group[J].Cancer,1987,59(11):1874-1881.endprint

[4] Chen M,Jiang G,Fu X,et al.Prognostic Factors for Local Control in Non–Small-Cell Lung Cancer Treated With Definitive Radiation Therapy[J].Am J Clin Oncol (CCT),2002,25(1):76-80.

[5] Furuse K,Fukuoka M,Kawahara M,et al.Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin,vindesine,and cisplatin in unresectable stage Ⅲ non-small-cell lung cancer[J].J Clin Oncol,1999,17(9):2692-2699.

[6] Zatloukal P,Petruzelka L,Zemanova M,et al.Concurrent versus sequential chemo-radiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer:a randomized study[J].Lung Cancer,2004,46(1):87-98.

[7] Belani CP,Choy H,Bonomi P,et al.Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer:a randomized phase Ⅱ locally advanced multi-modality protocol[J].J Clin Oncol,1999,23(25):5883-5891.

[8] 蒋国梁.现代肿瘤放疗学[M].上海:上海科学技术出版社,2003:174.

[9] 邱嵘,王玉祥,祝淑钗,等.肿瘤靶体积对Ⅲ期非小细胞肺癌三维适形放疗长期疗效的影响[J].肿瘤防治研究,2013,40(10):988-990.

[10] Langer CJ,Movsas B,Hudes R,et al.Induction paclitaxel and carboplatin followed by concurrent chemoradiotherapy in patients with unresectable,locally advanced non-small cell lung carcinoma:report of Fox Chase Cancer Centre study 94-001[J].Semin Oncol,1997,24(4 Suppl 12):S12-89-S12-95.

[11] 宋启斌,谢声强,徐利明,等.化疗与三维适形放疗同步治疗Ⅲ期非小细胞肺癌的临床观察[J].中华肿瘤杂志,2002,24(5):478-479.

(收稿日期:2014-08-04 本文编辑:郭静娟)endprint

[4] Chen M,Jiang G,Fu X,et al.Prognostic Factors for Local Control in Non–Small-Cell Lung Cancer Treated With Definitive Radiation Therapy[J].Am J Clin Oncol (CCT),2002,25(1):76-80.

[5] Furuse K,Fukuoka M,Kawahara M,et al.Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin,vindesine,and cisplatin in unresectable stage Ⅲ non-small-cell lung cancer[J].J Clin Oncol,1999,17(9):2692-2699.

[6] Zatloukal P,Petruzelka L,Zemanova M,et al.Concurrent versus sequential chemo-radiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer:a randomized study[J].Lung Cancer,2004,46(1):87-98.

[7] Belani CP,Choy H,Bonomi P,et al.Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer:a randomized phase Ⅱ locally advanced multi-modality protocol[J].J Clin Oncol,1999,23(25):5883-5891.

[8] 蒋国梁.现代肿瘤放疗学[M].上海:上海科学技术出版社,2003:174.

[9] 邱嵘,王玉祥,祝淑钗,等.肿瘤靶体积对Ⅲ期非小细胞肺癌三维适形放疗长期疗效的影响[J].肿瘤防治研究,2013,40(10):988-990.

[10] Langer CJ,Movsas B,Hudes R,et al.Induction paclitaxel and carboplatin followed by concurrent chemoradiotherapy in patients with unresectable,locally advanced non-small cell lung carcinoma:report of Fox Chase Cancer Centre study 94-001[J].Semin Oncol,1997,24(4 Suppl 12):S12-89-S12-95.

[11] 宋启斌,谢声强,徐利明,等.化疗与三维适形放疗同步治疗Ⅲ期非小细胞肺癌的临床观察[J].中华肿瘤杂志,2002,24(5):478-479.

(收稿日期:2014-08-04 本文编辑:郭静娟)endprint

[4] Chen M,Jiang G,Fu X,et al.Prognostic Factors for Local Control in Non–Small-Cell Lung Cancer Treated With Definitive Radiation Therapy[J].Am J Clin Oncol (CCT),2002,25(1):76-80.

[5] Furuse K,Fukuoka M,Kawahara M,et al.Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin,vindesine,and cisplatin in unresectable stage Ⅲ non-small-cell lung cancer[J].J Clin Oncol,1999,17(9):2692-2699.

[6] Zatloukal P,Petruzelka L,Zemanova M,et al.Concurrent versus sequential chemo-radiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer:a randomized study[J].Lung Cancer,2004,46(1):87-98.

[7] Belani CP,Choy H,Bonomi P,et al.Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer:a randomized phase Ⅱ locally advanced multi-modality protocol[J].J Clin Oncol,1999,23(25):5883-5891.

[8] 蒋国梁.现代肿瘤放疗学[M].上海:上海科学技术出版社,2003:174.

[9] 邱嵘,王玉祥,祝淑钗,等.肿瘤靶体积对Ⅲ期非小细胞肺癌三维适形放疗长期疗效的影响[J].肿瘤防治研究,2013,40(10):988-990.

[10] Langer CJ,Movsas B,Hudes R,et al.Induction paclitaxel and carboplatin followed by concurrent chemoradiotherapy in patients with unresectable,locally advanced non-small cell lung carcinoma:report of Fox Chase Cancer Centre study 94-001[J].Semin Oncol,1997,24(4 Suppl 12):S12-89-S12-95.

[11] 宋启斌,谢声强,徐利明,等.化疗与三维适形放疗同步治疗Ⅲ期非小细胞肺癌的临床观察[J].中华肿瘤杂志,2002,24(5):478-479.

(收稿日期:2014-08-04 本文编辑:郭静娟)endprint

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