安罗替尼联合放疗治疗复发难治小细胞肺癌1例报告及文献复习

doi:10.13481/j.1671-587x.20200231

摘要/Abstract

摘要： 目的：分析无法耐受进一步化疗的晚期复发难治小细胞肺癌（SCLC）患者应用安罗替尼联合放疗后取得满意疗效的治疗经过，阐明安罗替尼联合放疗对多线治疗后SCLC的有效性和安全性，为其治疗方案选择提供参考。方法：收集1例无法耐受进一步化疗的晚期复发难治SCLC患者的临床资料，结合相关文献复习，分析应用安罗替尼联合放射治疗的有效性和安全性。结果：患者，女性，70岁，既往高血压和糖尿病病史多年，以"咳嗽、气短"起病，经肺部CT和穿刺活检以及胸水脱落细胞学检查后诊断为广泛期SCLC（胸膜转移），并给予相关治疗。经过3线化疗后，患者反复出现粒细胞和血小板减少，无法耐受继续化疗，疾病进展迅速，出现呼吸困难无法平卧，给予患者安罗替尼口服和胸部放疗。放疗前查PET-CT示左肺上叶支气管开口高代谢结节，双侧肺门及纵膈多发放射性摄取增高淋巴结。给予安罗替尼12 mg每日1次口服3 d，放疗6 Gy/3 f后患者喘息明显好转，可平卧。患者诉头晕，血压168/80 mmHg，考虑与安罗替尼有关，且患者呼吸困难明显缓解，可平卧保证放疗安全实施，故停用安罗替尼。放疗38 Gy/19 f后，患者呼吸困难消失，复查左肺原发灶及转移淋巴结明显缩小。放疗后40 d复查肺部CT提示胸腔内病灶进一步缩小，后续于内科继续全身治疗。结论：对于无法耐受化疗或多线化疗失败的SCLC患者，安罗替尼联合放疗值得尝试，其疗效及安全性需大样本临床研究以证实。

关键词: 癌,小细胞肺, 安罗替尼, 放射疗法, 化学疗法

Abstract: Objective: To analyze the treatment of a patient with recurrent and refractory small cell lung cancer(SCLC) intolerable further chemotherapy who gained significant efficacy by anlotinib combined with thoracic radiotherapy and to clarify the efficacy and safety of anlotinib combined with radiotherapy in the SCLC patients, and to provide the reference for the selection of treatment program of these patients. Methods: The clinical data of one patient with advanced recurrent and refractory SCLC who could not tolerate further chemotherapy were collected, and the related literatures were reviewed to analyze the efficacy and safety of anlotinib combined with thoracic radiotherapy. Results: The patient was a 70-year-old woman who had a long histroy of hypertention and diabetes,and presented with cough and shortness of breath.Based on the chest CT,biopsy and pleural effusion cytology,the patient was definitely diagnosed as extensive stage of SCLC(pleural metastasis) and then underwent a series of treatments. After three lines of chemotherapy regimens, the patient was unable to tolerate the continued chemotherapy due to the repeated reduce of neutrophil and platelet, and the disease progressed rapidly. Dyspnea aggravated,and the patient was unable to lie. Anlotinib combined with thoracic radiotherapy was initiated.Before radiotherapy,the PET-CT results demonstrated the hypermetabolic lesions including primary tumor located in upper lobe of left lung and bilateral hilar and mediastinal lymph nodes,bilateral pleural effusion.The patient was administrated orally with anlotinib 12 mg once per day for 3 d after thoracic radiotherapy of 6 G/3 f, the patient's wheeze was improved obviously and she could lie flat.However,she complained of dizziness with an increased blood pressure of 168/80 mmHg.Considering that it was related to anlotinib,and the patient's dyspnea was obviously relieved at present to ensure the safe implementation of radiotherapy,so anlotinib was suspended.After irradiation with 38 Gy/19 f,the patient's dyspnea disappeared completely;the primary tumor and metastatic lymph nodes shrank significantly. The CT results showed the intrathoracic lesions were shrank 40 d after radiotherapy;then the patient continued to system therapy. Conclusion: For the patients with SCLC unable to tolerate chemotherapy or progressed after multiple lines of chemotherapy, anlotinib combined with thoracic radiotherapy is promising.In the future,large-scaled clinical trials should be initiated to testify the efficacy and safety of anlotinib combined with thoracic radiotherapy.

Key words: small cell lung cancer, anlotinib, radiotherapy, chemotherapy

中图分类号:

R734.2

刘慧, 马云飞, 刘百龙, 刘敏. 安罗替尼联合放疗治疗复发难治小细胞肺癌1例报告及文献复习[J]. 吉林大学学报(医学版), 2020, 46(02): 394-398.

LIU Hui, MA Yunfei, LIU Bailong, LIU Min. Anlotinib combined with thoracic radiotherapy in treatment of recurrent and refractory small cell lung cancer: A case report and literature review[J]. Journal of Jilin University(Medicine Edition), 2020, 46(02): 394-398.

参考文献

[1] BEPLER G,BEQUM M,SIMON G R. Molecular analysis-based treatment strategies for non-small cell lung cancer[J].Cancer Control,2008,15(2):130-139.
[2] 魏雨晴,吕镗烽,刘红兵,等.肺癌分子诊断及其研究进展[J].中国实用内科杂志,2019,39(5):407-411.
[3] GOVINDAN R, PAGE N, MORGENSZTERN D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years:analysis of the surveillance, epidemiologic, and end results database[J]. J Clin Oncol, 2006,24(28):4539-4544.
[4] JETT J R, SCHILD S E, KESLER K A, et al. Treatment of small cell lung cancer:Diagnosis and management of lung cancer, 3rd ed:American College of Chest Physicians evidence-based clinical practice guidelines[J].Chest, 2013,143(5 Suppl):e400S-e419S.
[5] JEREMIC B, SHIBAMOTO Y, NIKOLIC N,et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer:A randomized study[J]. J Clin Oncol,1999,17(7):2092-2099.
[6] PODOLOFF D A, BALL D W, BEN-JOSEF E, et al. NCCN task force:clinical utility of PET in a variety of tumor types[J]. J Natl Compr Canc Netw, 2009,7(Suppl 2):S1-S26.
[7] BRADLEY J D, DEHDASHTI F, MINTUN M A, et al. Positron emission tomography in limited-stage small-cell lung cancer:a prospective study[J]. J Clin Oncol, 2004,22(16):3248-3254.
[8] FISCHER B M, MORTENSEN J, LANGER S W,et al. A prospective study of PET/CT in initial staging of small-cell lung cancer:comparison with CT, bone scintigraphy and bone marrow analysis[J]. Ann Oncol, 2007,18(2):338-345.
[9] KALEMKERIAN G P. Staging and imaging of small cell lung cancer[J]. Cancer Imaging, 2011,11(1):253-258.
[10] MAMDANI H, INDURU R, JALAL S I. Novel therapies in small cell lung cancer[J]. Transl Lung Cancer Res,2015,4(5):533-544.
[11] CUI X, SONG P, ZHANG L. New advances in the treatment for small cell lung cancer[J]. Zhongguo Fei Ai Za Zhi, 2019,22(6):355-362.
[12] HAN B H, LI K, WANG Q M, et al. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer:the ALTER 0303 phase 3 randomized clinical trial[J]. JAMA Oncol,2018,4(11):1569-1575.
[13] YANG S, ZHANG Z, WANG Q. Emerging therapies for small cell lung cancer[J]. J Hematol Oncol,2019,12(1):47.
[14] HAMMING L C, SLOTMAN B J, VERHEUL H M W,et al. The clinical application of angiostatic therapy in combination with radiotherapy:past, present, future[J]. Angiogenesis. 2017,20(2):217-232.
[15] DINGS R P, LOREN M, HEUN H,et al. Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization[J]. Clin Cancer Res,2007,13(11):3395-3402.
[16] JAIN R K. Molecular regulation of vessel maturation[J]. Nat Med,2003,9(6):685-693.
[17] JAIN R K.Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J]. Science,2005,307(5706):58-62.
[18] MATSUMOTO S, BATRA S, SAITO K, et al.Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia[J]. Cancer Res,2011,71(20):6350-6359.
[19] GUPTA V K, JASKOWIAK N T, BECKETT M A,et al. Vascular endothelial growth factor enhances endothelial cell survival and tumor radioresistance[J]. Cancer J,2002, 8(1):47-54.
[20] GARCIA-BARROS M, PARIS F, CORDON-CARDO C,et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis[J]. Science,2003,300(5622):1155-1159.