小细胞肺癌二线治疗进展

doi:10.3760/cma.j.issn.1673-422X.2017.04.013

摘要/Abstract

摘要： 小细胞肺癌（SCLC）是一种恶性程度较高的肿瘤，一线放化疗非常敏感，但容易复发转移，预后差。SCLC二线治疗进展缓慢，拓扑替康是目前唯一被美国食品和药物管理局批准的二线标准治疗药物。大量关于分子靶向治疗和免疫治疗的研究正在进行中，但大多疗效欠佳。2016年美国临床肿瘤学会年会上公布的靶向Delta样蛋白3的抗体药物耦联物rovalpituzumab tesirine（Rova-T）显示了良好的抗肿瘤活性，似乎为分子靶向治疗带来了新的曙光。

关键词: 肺肿瘤, 癌, 小细胞, 再治疗, 药物疗法

Abstract: Small cell lung cancer (SCLC) is a highly malignant tumor, which is very sensitive to firstline chemotherapy, but easy to recurrence and metastasis early. So it always has poor prognosis. Secondline therapy for SCLC develops slowly. Topotecan is the only drug approved by US Food and Drug Administration as a secondline chemoradiotherapy. Numerous studies on molecular targeted therapy and immunotherapy are being carried out, but most of them have no or little benefit. Rovalpituzumab tesirine (RovaT) targeted antibodydrug conjugate (ADC) which is published at the 2016 American Society of Clinical Oncology Annual Meeting shows a good antitumor activity, which seems to bring a new dawn of molecular targeted therapy.

Key words: Lung neoplasms, Carcinoma, small cell, Retreatment, Drug therapy

杨洪娟,谢丛华. 小细胞肺癌二线治疗进展[J]. 国际肿瘤学杂志, 2017, 44(4): 290-293.

Yang Hongjuan, Xie Conghua.. Advances of second-line therapy for small-cell lung cancer[J]. Journal of International Oncology, 2017, 44(4): 290-293.

参考文献

［1］ Spigel DR, Socinski MA. Rationale for chemotherapy, immunotherapy, and checkpoint blockade in SCLC: beyond traditional treatment approaches［J］. J Thorac Oncol, 2013, 8(5): 587-598. DOI: 10.1097/JTO.0b013e318286cf88. ［2］ Parsons A, Daley A, Begh R, et al. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis［J］. BMJ, 2010, 340: b5569. DOI: 10.1136/bmj.b5569. ［3］ Hartwell D, Jones J, Loveman E, et al. Topotecan for relapsed small cell lung cancer: a systematic review and economic evaluation［J］. Cancer Treat Rev, 2011, 37(3): 242-249. DOI: 10.1016/j.ctrv.2010.07.005. ［4］ Heist RS, Fain J, Chinnasami B, et al. PhaseⅠ/Ⅱ study of AT-101 with topotecan in relapsed and refractory small cell lung cancer［J］. J Thorac Oncol, 2010, 5(10): 1637-1643. DOI: 10.1097/JTO.0b013e3181e8f4dc. ［5］ Spigel DR, Waterhouse DM, Lane S, et al. Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an openlabel multicenter single-arm phase Ⅱ study［J］. Clin Lung Cancer, 2013, 14(4): 356-363. DOI: 10.1016/j.cllc.2012.12.003. ［6］ Ettinger DS, Jotte R, Lorigan P, et al. Phase Ⅱ study of amrubicin as secondline therapy in patients with platinumrefractory smallcell lung cancer［J］. J Clin Oncol, 2010, 28(15): 2598-2603. DOI: 10.1200/JCO.2009.26.7682. ［7］ von Pawel J, Jotte R, Spigel DR, et al. Randomized phase Ⅲ trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer［J］. J Clin Oncol, 2014, 32(35): 4012-4019. DOI: 10.1200/JCO.2013.54.5392. ［8］ Sevinc A, Kalender ME, Altinbas M, et al. Irinotecan as a secondline monotherapy for small cell lung cancer［J］. Asian Pac J Cancer Prev, 2011, 12(4): 1055-1059. ［9］赵明利, 毕清, 任宏轩, 等. 伊立替康与拓扑替康二线治疗43例小细胞肺癌的临床观察［J］. 中国癌症杂志, 2011, 21(2): 156158. DOI: 10.3969/j.issn.1007-3969.2011.02.016. ［10］ Jeong J, Cho BC, Sohn JH, et al. Belotecan for relapsing small-cell lung cancer patients initially treated with an irinotecan-containing chemotherapy: a phase Ⅱ trial［J］. Lung Cancer, 2010, 70(1): 77-81. DOI: 10.1016/j.lungcan.2010.01.006. ［11］ Kim GM, Kim YS, Ae Kang Y, et al. Efficacy and toxicity of belotecan for relapsed or refractory small cell lung cancer patients［J］. J Thorac Oncol, 2012, 7(4): 731-736. DOI: 10.1097/JTO.0b013e31824b23cb. ［12］ Goto K, Ohe Y, Shibata T, et al. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as secondline treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, openlabel, randomised phase 3 trial［J］. Lancet Oncol, 2016, 17(8): 1147-1157. DOI: 10.1016/S1470-2045(16)30104-8. ［13］ Jalal S, Bedano P, Einhorn L, et al. Paclitaxel plus bevacizumab in patients with chemosensitive relapsed small cell lung cancer: a safety, feasibility, and efficacy study from the Hoosier Oncology Group［J］. J Thorac Oncol, 2010, 5(12): 2008-2011. DOI: 10.1097/JTO.0b013e3181f77b6e. ［14］ Mountzios G, Emmanouilidis C, Vardakis N, et al. Paclitaxel plus bevacizumab in patients with chemoresistant relapsed small cell lung cancer as salvage treatment: a phase Ⅱ multicenter study of the Hellenic Oncology Research Group［J］. Lung Cancer, 2012, 77(1): 146-150. DOI: 10.1016/j.lungcan.2012.02.002. ［15］ Waterhouse DM, Morgan SK, Spigel DR, et al. Phase Ⅱ study of oral topotecan plus bevacizumab (topo-bev) for second-line treatment of small cell lung cancer (SCLC)［J］. J Clin Oncol, 2010, 28 Suppl 15s: abstr 7055. DOI: 10.1200/jco.2010.28.15_suppl.7055. ［16］ Ready NE, Pang HH, Gu L, et al. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: a randomized, doubleblind, placebo-controlled phase Ⅱ study-CALGB 30504 (Alliance)［J］. J Clin Oncol, 2015, 33(15): 1660-1665. DOI: 10.1200/JCO.2014.57.3105. ［17］ Han JY, Kim HY, Lim KY, et al. A phase Ⅱ study of sunitinib in patients with relapsed or refractory small cell lung cancer［J］. Lung Cancer, 2013, 79(2): 137-142. DOI: 10.1016/j.lungcan.2012.09.019. ［18］ Rudin CM, Hann CL, Garon EB, et al. Phase Ⅱ study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer［J］. Clin Cancer Res, 2012, 18(11): 3163-3169. DOI: 10.1158/1078-0432.CCR-11-3090. ［19］ Wainberg ZA, Rafii S, Ramanathan K, et al. Safety and antitumor activity of the PARP inhibitor BMN673 in a phase Ⅰ trial recruiting metastatic small-cell lung cancer (SCLC) and germline BRCAmutation carrier cancer patients［J］. J Clin Oncol, 2014, 32 Suppl 5: abstr 7522. ［20］ Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo［J］. Sci Transl Med, 2015, 7(302): 302ra136. DOI: 10.1126/scitranslmed.aac9459. ［21］ Rudin CM, Pietanza MC, Bauer TM, et al. Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)targeted antibodydrug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC)［J］. J Clin Oncol, 2016, 34 Suppl: abstr LBA8505. ［22］ Ott PA, Fernandez MEE, Hiret S, et al. Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): preliminary safety and efficacy results from KEYNOTE028［J］. J Clin Oncol, 2015, 33 Suppl: abstract 7502. ［23］ Antonia SJ, LópezMartin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial［J］. Lancet Oncol, 2016, 17(7): 883-895. DOI: 10.1016/S1470-2045(16)30098-5.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	钱晓涛, 石子宜, 胡格, 吴晓维. Ⅲ~ⅣA期食管鳞状细胞癌放化疗后行巩固化疗的疗效：一项真实世界临床研究[J]. 国际肿瘤学杂志, 2024, 51(6): 326-331.
[3]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[4]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[5]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[6]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华. 炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[7]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[8]	顾芳萌, 徐晨阳, 雷大鹏. 人工智能辅助电子喉镜检查在喉癌及喉癌前病变诊治中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(5): 303-307.
[9]	张文馨, 夏泠, 彭晋, 周福祥. 甲胎蛋白升高型胃肝样腺癌1例并文献复习[J]. 国际肿瘤学杂志, 2024, 51(5): 312-315.
[10]	王昆, 周中新, 臧其威. 血清TGF-β1、VEGF水平对非小细胞肺癌患者单孔胸腔镜根治术后复发的预测价值[J]. 国际肿瘤学杂志, 2024, 51(4): 198-203.
[11]	杨毫, 施贵冬, 张程城, 张跃, 张力文, 付茂勇. 信迪利单抗与替雷利珠单抗在进展期食管鳞状细胞癌新辅助治疗中的疗效及安全性对比[J]. 国际肿瘤学杂志, 2024, 51(4): 210-216.
[12]	姚益新, 沈煜霖. 血清SOCS3、TXNIP水平对肝细胞癌TACE治疗预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(4): 217-222.
[13]	胡婷婷, 王越华. 电子鼻与线虫鼻——新型早期癌症筛查工具[J]. 国际肿瘤学杂志, 2024, 51(4): 223-226.
[14]	张栋岩, 王品, 魏秋亚, 邓成伍, 魏相相, 高远飞, 王琛. 索凡替尼靶向联合卡培他滨和奥沙利铂治疗肝内胆管癌术后患者1例及文献复习[J]. 国际肿瘤学杂志, 2024, 51(4): 249-253.
[15]	严爱婷, 王翠竹, 刘春桂, 鲁小敏. 卡瑞利珠单抗与信迪利单抗治疗晚期非小细胞肺癌的临床疗效及安全性分析[J]. 国际肿瘤学杂志, 2024, 51(3): 137-142.