Research progress on recombinant human endostatin combined with radiotherapy and / or chemotherapy in the treatment of cervical cancer
Li Xin1,2, Hu Lijun2, Yu Jingping1,2,3
1Graduate School of Bengbu Medical College,Bengbu 233000, China; 2Department of radiotherapy, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou 213003, China; 3Department of radiotherapy, Shuguang Hospital, the Affiliated Hospital of Shanghai University of Chinese Traditional Medicine, Shanghai 201203, China
Abstract：Cervical cancer is one of the most common malignant tumors in women worldwide. Locally advanced cervical cancer is mainly treated with radiotherapy and chemotherapy, but there are problems such as high recurrence rate and low survival rate. Bevacizumab, an angiogenic inhibitor that acts on vascular endothelial growth factor (VEGF), has been recommended by the National Comprehensive Cancer Network (NCCN) guidelines for the first-line treatment of recurrent / metastatic advanced cervical cancer in 2013. In recent years, the development of new targeted drugs for angiogenesis inhibitors, such as endostatin, has further optimized the new targeted therapy strategy for patients with locally advanced and advanced cervical cancer. Recombinant human endostatin (endostar) is a novel anti-angiogenesis drug independently developed by Chinese scientists. Although it has been applied in the treatment of cervical cancer, it needs to be further confirmed by high level evidence based medical evidence whether it can become a new option for targeted treatment of cervical cancer. In this article, clinical research progress on the treatment of cervical cancer by endostar combined with radiotherapy and / or chemotherapy was reviewed, aiming to provide reference for the optimization of cervical cancer treatment strategy.
Li Xin,Hu Lijun,Yu Jingping. Research progress on recombinant human endostatin combined with radiotherapy and / or chemotherapy in the treatment of cervical cancer[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 75-80.
[1] Bray F, Ferlay J, Soerjomataram I, et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018,68(6):394-424. DOI: 10.3322/caac.21492. [2] Naga Ch P, Gurram L, Chopra S, et al.The management of locally advanced cervical cancer[J]. Curr Opin Oncol, 2018,30(5):323-329. DOI: 10.1097/CCO.0000000000000471. [3] Zhang SL, Han CB, Sun L, et al.Efficacy and safety of recombinant human endostatin combined with radiotherapy or chemoradiotherapy in patients with locally advanced non-small cell lung cancer: a pooled analysis[J]. Radiat Oncol, 2020,15(1):205. DOI: 10.1186/s13014-020-01646-9. [4] Cohen PA, Jhingran A, Oaknin A, et al.Cervical cancer[J]. Lancet, 2019,393(10167):169-182. DOI: 10.1016/S0140-6736(18)32470-X. [5] Garcia J, Hurwitz HI, Sandler AB, et al.Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook[J]. Cancer Treat Rev, 2020,86:102017. DOI: 10.1016/j.ctrv.2020.102017. [6] Chen J, Yao Q, Huang M, et al.A randomized phase III trial of neoadjuvant recombinant human endostatin, docetaxel and epirubicin as first-line therapy for patients with breast cancer (CBCRT01)[J]. Int J Cancer, 2018,142(10):2130-2138. DOI: 10.1002/ijc.31217. [7] Zhao X, Wen X, Wei W, et al.Predictors for the efficacy of endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC[J]. Cancer Biomark, 2017,21(1):169-177. DOI: 10.3233/CBM-170565. [8] Jin Y, Wei L, Jiang Q, et al.Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograft zebrafish model[J]. Sci Rep, 2018,8(1):15837. DOI: 10.1038/s41598-018-34030-5. [9] Zhang K, Wang Y, Yu X, et al.Recombinant human endostatin combined with radiotherapy inhibits colorectal cancer growth[J]. BMC Cancer, 2017,17(1):899. DOI: 10.1186/s12885-017-3903-3. [10] Li K, Shi M, Qin S.Current status and study progress of recombinant human endostatin in cancer treatment[J]. Oncol Ther, 2018,6(1):21-43. DOI: 10.1007/s40487-017-0055-1. [11] Pan F, Yang W, Li W, et al.Conjugation of gold nanoparticles and recombinant human endostatin modulates vascular normalization via interruption of anterior gradient 2-mediated angiogenesis[J]. Tumour Biol, 2017,39(7):1010428317708547. DOI: 10.1177/1010428317708547. [12] 农先胜,黄显实,莫艳芳,等. 恩度联合吉西他滨治疗晚期宫颈癌的近期疗效观察[J]. 广西医科大学学报,2015,32(4):646-648. DOI:10.16190/j.cnki.45-1211/r.2015.04.045. Nong XS, Huang XS, Mo YF, et al. Grace degree combination gemcitabine treatment of advanced cervical cancer in the near future curative effect observation[J]. Journal of Guangxi Medical University, 2015,32(4):646-648. DOI: 10.16190/j.cnki.45-1211/r.2015.04.045. [13] Guo F, Chen C, Liang Y, et al. Efficacy of the combination of endostar with chemotherapy on stage IVb and recurrent metastatic cervical cancer[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2020,45(12):1412-1418. DOI: 10.11817/j.issn.1672-7347.2020.190321. [14] Kong SY, Huang K, Zeng C, et al.The association between short-term response and long-term survival for cervical cancer patients undergoing neoadjuvant chemotherapy: a system review and meta-analysis[J]. Sci Rep, 2018,8(1):1545. DOI: 10.1038/s41598-018-19948-0. [15] Wang YC, Hu DY, Hu XM, et al.Assessing the early response of advanced cervical cancer to neoadjuvant chemotherapy using intravoxel incoherent motion diffusion-weighted magnetic resonance imaging: a pilot study[J]. Chin Med J (Engl), 2016,129(6):665-671. DOI: 10.4103/0366-6999.177995. [16] Guan LM.Endostar rebuilding vascular homeostasis and enhancing chemotherapy efficacy in cervical cancer treatment[J]. Onco Targets Ther, 2020,13:12811-12827. DOI: 10.2147/OTT.S277644. [17] 柯庆华, 周世琼, 胡艳, 等. 重组人血管内皮抑制素(恩度)联合放疗同步治疗中晚期宫颈癌48例的近期疗效[J].现代肿瘤医学,2011,19(10):2066-2068. DOI: 10.3969/j.issn.1672-4992.2011.10.54. Ke QH, Zhou SQ, Hu Y, et al.The efficacy of endostar combined with radiotherapy for advanced cervical cancer[J]. Journal of Modern Oncology, 2011,19(10):2066-2068. DOI: 10.3969/j.issn.1672-4992.2011.10.54. [18] 刘晨, 杨蓉, 张凡, 等. 重组人血管内皮抑制素促进子宫颈鳞状细胞癌放疗效果的临床观察[J].中国计划生育学杂志, 2013,21(3):188-191. DOI: 10.3969/j.issn.1004-8189.2013.03. Liu C, Yang R, Zhang F, et al.Endostatin improves the effect of radiotherapy in the treatment of squamous carcinoma of the uterine cervix[J]. Chinese Journal of Family Planning, 2013,21(3):188-191. DOI: 10.3969/j.issn.1004-8189.2013.03. [19] Arbyn M, Weiderpass E, Bruni L, et al.Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis[J]. Lancet Glob Health, 2020,8(2):e191-e203. DOI: 10.1016/S2214-109X(19)30482-6. [20] Multhoff G, Vaupel P.Hypoxia compromises anti-cancer immune responses[J]. Adv Exp Med Biol, 2020,1232:131-143. DOI: 10.1007/978-3-030-34461-0_18. [21] 刘亮, 刘毅, 夏铀铀, 等. 内皮抑素对NSCLC细胞系中VEGF受体2表达的影响及其放射增敏效应机制研究[J].中华放射肿瘤学杂志, 2015,(5):593-597. DOI: 10.3760/cma.j.issn.1004-4221.2015.05.030. Liu L, Liu Y, Xia YY, et al.Impacts of endostatin on expression of vascular endothelial growth factor receptor-2 in non-small cell lung cancer cells and mechanisms underlying its radiosensitizing effect[J]. Chinese Journal of Radiation Oncology, 2015,(5):593-597. DOI: 10.3760/cma.j.issn.1004-4221.2015.05.030. [22] 杨晓军, 李强, 庄翔, 等. VEGFR基因表达与接受恩度治疗的IIIa期非小细胞肺癌疗效相关性研究[J].肿瘤预防与治疗,2016,29(6):320-322. DOI: 10.3969/j.issn.1674-0904. 2016.06.005. Yang XJ, Li Q, Zhuang X, et al.Study on the relationship between VEGFR gene expression and endostar therapy in stage IIIa non-small cell lung cancer[J]. Journal of Cancer Control and Treatment, 2016,29(6):320-322. DOI: 10.3969/j.issn.1674-0904.2016.06.005. [23] Liu GF, Chang H, Li BT, et al.Effect of recombinant human endostatin on radiotherapy for esophagus cancer[J]. Asian Pac J Trop Med, 2016,9(1):86-90. DOI: 10.1016/j.apjtm.2015.12.017. [24] Yan H, Guo W, Li K, et al.Combination of DESI2 and endostatin gene therapy significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis[J]. Exp Cell Res, 2018,371(1):50-62. DOI: 10.1016/j.yexcr.2018.07.040. [25] Meng FJ, Wang S, Yan YJ, et al.Recombined humanized endostatin-induced suppression of HMGB1 expression inhibits proliferation of NSCLC cancer cells[J]. Thorac Cancer, 2019,10(1):90-95. DOI: 10.1111/1759-7714.12905. [26] Toulany M. Targeting DNA double-strand break repair pathways to improve radiotherapy response[J]. Genes (Basel), 2019,10(1)DOI: 10.3390/genes10010025. [27] 赵金艳, 董晓兰, 高萍, 等. 重组人血管内皮抑制素联合羟基脲同步放化疗治疗中晚期宫颈癌的疗效观察[J].中国实用医药,2012,7(2):65-66. DOI: 10.3969/j.issn.1673-7555.2012.02.044. Zhao JY, Dong XL, Gao P, et al.Efficacy of recombinant human endostatin combined with hydroxyurea concurrent chemoradiotherapy in the treatment of advanced cervical cancer[J]. Chinese Practical Medicine, 2012,7(2):65-66. DOI: 10.3969/j.issn.1673-7555.2012.02.044. [28] 柯庆华, 周世琼, 杜伟, 等. 同步放化疗联合重组人血管内皮抑制素治疗中晚期宫颈癌52例疗效分析[J].实用癌症杂志,2012,27(4):373-375. DOI: 10.3969/j.issn.1001-5930.2012.04.014. Ke QH, Zhou SQ, Du W, et al.The early efficacy of the endostar combined with chemoradiotherapy to the advanced cervical cancer[J]. The Practical Journal of Cancer, 2012,27(4):373-375. DOI: 10.3969/j.issn.1001-5930.2012.04.014. [29] 刘兴京, 侯兵, 宋晓军, 等. 恩度联合同步放化疗治疗III期巨块型宫颈癌的临床疗效观察[J].武警后勤学院学报(医学版),2013,22(3):178-181. DOI: 10.3969/j.issn.2095-3720.2013.03.006. Liu XJ, Hou B, Song XJ, et al.The efficacy of endostar combined with co-chemoradiotherapy for stage III bulky cervical cancer[J]. Journal of Logistics University of PAP (Medical Sciences), 2013,22(3):178-181. DOI: 10.3969/j.issn.2095-3720.2013.03.006. [30] 罗菊玉. 重组人血管内皮抑制素辅助治疗中晚期宫颈癌效果观察[J].山东医药,2016,56(42):72-74. DOI: 10.3969/j.issn.1002-266X.2016.42.025. Luo JY. Effect of recombinant human endostatin in adjuvant treatment of advanced cervical cancer[J]. Shandong Medical Journal, 2016,56(42):72-74. DOI: 10.3969/j.issn.1002-266X.2016.42.025. [31] 范亚峰, 虞中平, 崔晓燕, 等. 重组人血管内皮抑素联合放化疗治疗宫颈癌的疗效分析[J].中国药物与临床,2017,17(6):865-868. DOI: 10.11655/zgywylc2017.06.033. Fan YF, Yu ZP, Cui XY, et al. Efficacy analysis of recombinant human endostatin combined with chemoradiotherapy in the treatment of cervical cancer[J]. Chinese Remedies & Clinics, 2017,17(06):865-868. DOI: 10.11655/zgywylc2017.06.033. [32] 陈娟, 付虹霞. 恩度联合放、化疗对中晚期宫颈癌疗效及CD4+T细胞平衡失调的影响[J].肿瘤药学,2020,10(06):709-713. DOI: 10.3969/j.issn.2095-1264.2020.06.13. Chen J, Fu HX. The efficacy of endostar combined with radiotherapy and chemotherapy and its effects on imbalance of CD4+ T cells of advanced cervical cancer patients[J]. Anti-Tumor Pharmacy, 2020,10(6):709-713. DOI: 10.3969/j.issn.2095-1264.2020.06.13. [33] 李金燕. 恩度联合同步放化疗在局部晚期宫颈癌治疗中的效果及对血清VEGF、SCCA、CYFRA21-1等的影响[J].实用癌症杂志,2021,36(07):1136-1139. DOI: 10.3969/j.issn.1001-5930.2021.07.023. Li JY. The effect of ondo combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer and its effect on serum VEGF,SCCA, CYFRA21-1[J]. The Practical Journal of Cancer, 2021,36(07):1136-1139. DOI: 10.3969/j.issn.1001-5930.2021.07.023. [34] Shu H, Dong Y, Xu Z, et al.The efficacy and safety of continuous intravenous endostar treatment combined with concurrent chemoradiotherapy in patients with locally advanced cervical squamous cell carcinoma: a randomized controlled trial[J]. Front Oncol, 2021,11:723193. DOI: 10.3389/fonc.2021.723193. [35] Lu H, Wu Y, Liu X, et al.Endostar, an anti-angiogenesis inhibitor, combined with chemoradiotherapy for locally advanced cervical cancer[J]. Oncol Res, 2020, 28(9): 929-944. DOI:10.3727/096504021×16318716607908. [36] Zhang K, Wang H, Wang Z, et al.Intensity-modulated radiation therapy (IMRT)-based concurrent chemoradiotherapy (CCRT) with endostar in patients with pelvic locoregional recurrence of cervical cancer: results from a hospital in the Qinghai-Tibet plateau[J]. Medicine (Baltimore), 2020,99(49):e21966. DOI: 10.1097/MD.0000000000021966. [37] Williamson CW, Liu HC, Mayadev J, et al.Advances in external beam radiation therapy and brachytherapy for cervical cancer[J]. Clin Oncol (R Coll Radiol), 2021,33(9):567-578. DOI: 10.1016/j.clon.2021.06.012. [38] Lin LL, Kirk M, Scholey J, et al.Initial report of pencil beam scanning proton therapy for posthysterectomy patients with gynecologic cancer[J]. Int J Radiat Oncol Biol Phys, 2016,95(1):181-189. DOI: 10.1016/j.ijrobp.2015.07.2205. [39] Vyfhuis M, Fellows Z, McGovern N, et al. Preserving endocrine function in premenopausal women undergoing whole pelvis radiation for cervical cancer[J]. Int J Part Ther, 2019,6(1):10-17. DOI: 10.14338/IJPT-D-19-00061.1. [40] Pötter R, Tanderup K, Schmid MP, et al.MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study[J]. Lancet Oncol, 2021,22(4):538-547. DOI: 10.1016/S1470-2045(20)30753-1. [41] Naumann RW, Hollebecque A, Meyer T, et al.Safety and efficacy of nivolumab monotherapy in recurrent or metastatic cervical, vaginal, or vulvar carcinoma: results from the phase I/II CheckMate 358 trial[J]. J Clin Oncol, 2019,37(31):2825-2834. DOI: 10.1200/JCO.19.00739. [42] Ott PA, Bang YJ, Piha-Paul SA, et al.T-cell-inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028[J]. J Clin Oncol, 2019,37(4):318-327. DOI: 10.1200/JCO.2018.78.2276. [43] Marabelle A, Fakih M, Lopez J, et al.Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study[J]. Lancet Oncol, 2020,21(10):1353-1365. DOI: 10.1016/S1470-2045(20)30445-9. [44] Schepisi G, Casadei C, Toma I, et al. Immunotherapy and its development for gynecological (ovarian, endometrial and cervical) tumors: from immune checkpoint inhibitors to chimeric antigen receptor (CAR)-T cell therapy[J]. Cancers (Basel), 2021,13(4)DOI: 10.3390/cancers13040840. [45] Wu J, Zhao X, Sun Q, et al.Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model[J]. Biomed Pharmacother, 2020,125:109746. DOI: 10.1016/j.biopha.2019.109746. [46] Huinen ZR, Huijbers E, van Beijnum JR, et al. Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes[J]. Nat Rev Clin Oncol, 2021,18(8):527-540. DOI: 10.1038/s41571-021-00496-y.
2023, Vol. 32 
