Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | NSCLC | Research

Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy

Authors: Kuifei Chen, Shuling Li, Meng Chen, Zhicheng Jin, Xuefeng Sun, Suna Zhou, Haihua Yang

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Background

CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients.

Methods

This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP.

Results

There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC.

Conclusions

When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.
Literature
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.PubMedCrossRef
2.
Janssen-Heijnen MLG, van Erning FN, De Ruysscher DK, Coebergh JWW. Groen HJM: Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis. Ann Oncol. 2015;26(5):902–7.PubMedCrossRef
3.
Semrau S, Klautke G, Virchow JC, Kundt G, Fietkau R. Impact of comorbidity and age on the outcome of patients with inoperable NSCLC treated with concurrent chemoradiotherapy. Respir Med. 2008;102(2):210–8.PubMedCrossRef
4.
Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, Kubik A, Krepela E, Fiala P, Pecen L. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer. 2004;46(1):87–98.PubMedCrossRef
5.
Patel AB, Edelman MJ, Kwok Y, Krasna MJ, Suntharalingam M. Predictors of acute esophagitis in patients with non-small-cell lung carcinoma treated with concurrent chemotherapy and hyperfractionated radiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2004;60(4):1106–12.PubMedCrossRef
6.
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342–50.PubMedCrossRef
7.
Shaverdian N, Offin MD, Rimner A, Shepherd AF, Wu AJ, Rudin CM, Hellmann MD, Chaft JE, Gomez DR. Utilization and factors precluding the initiation of consolidative durvalumab in unresectable stage III non-small cell lung cancer. Radiother Oncol. 2020;144:101–4.PubMedCrossRef
8.
Zhai Y, Ma H, Hui Z, Zhao L, Li D, Liang J, Wang X, Xu L, Chen B, Tang Y, et al. HELPER study: A phase II trial of continuous infusion of endostar combined with concurrent etoposide plus cisplatin and radiotherapy for treatment of unresectable stage III non-small-cell lung cancer. Radiother Oncol. 2019;131:27–34.PubMedCrossRef
9.
Xu H, Lv D, Meng Y, Wang M, Wang W, Zhou C, Zhou S, Chen X, Yang H. Endostar improved efficacy of concurrent chemoradiotherapy with vinorelbine plus carboplatin in locally advanced lung squamous cell carcinoma patients with high serum Lp(a) concentration. Ann Palliat Med. 2020;9(2):298–307.PubMedCrossRef
10.
Zhang SL, Han CB, Sun L, Huang LT, Ma JT. 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. Radiat Oncol. 2020;15(1):205.PubMedPubMedCentralCrossRef
11.
Jianbo Zhu, Guangpeng Chen, Kai Niu, Yongdong Feng, Lijiao Xie, Si Qin, Zhongyu Wang, Jixi Li, Song Lang. Zhuo Wenlei et al Efficacy and safety of recombinant human endostatin during peri-radiotherapy period in advanced non-small-cell lung cancer. Future Oncology. 2022;18(9):1077–87.CrossRef
12.
Hillman GG, Lonardo F, Hoogstra DJ, Rakowski J, Yunker CK, Joiner MC, Dyson G, Gadgeel S, Singh-Gupta V. Axitinib Improves Radiotherapy in Murine Xenograft Lung Tumors. Transl Oncol. 2014;7(3):400–9.PubMedPubMedCentralCrossRef
13.
Gao RW, Day CN, Yu NY, Bush A, Amundson AC, Prodduturvar P, Majeed U, Butts E, Oliver T, Schwecke AJ, et al. Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab. Lung Cancer. 2022;170:58–64.PubMedCrossRef
14.
Tsujino K, Hirota S. Masahiro Endo, Kayoko Obayashi, Kotani Y, Miyako Satouchi, Kado T, Takada Y: Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. J Radiat Oncol Biol Phys. 2003;55(1):110–5.CrossRef
15.
Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, Bradley JD, Kim TH, Ramella S, Marks LB, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2013;85(2):444–50.PubMedCrossRef
16.
17.
Ma H, Peng F, Xu Y, Bao Y, Hu X, Wang J, Fang M, Kong Y, Dong B, Chen M. Five-year survival rate analysis: the combination of fortnightly-administration of endostar and concurrent chemoradiotherapy versus concurrent chemoradiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer. Ann Palliat Med. 2021;10(7):7560–70.PubMedCrossRef
18.
Sun XJ, Deng QH, Yu XM, Ji YL, Zheng YD, Jiang H, Xu YP, Ma SL. A phase II study of Endostatin in combination with paclitaxel, carboplatin, and radiotherapy in patients with unresectable locally advanced non-small cell lung cancer. BMC cancer. 2016;16:266.PubMedPubMedCentralCrossRef
19.
Bao Y, Peng F, Zhou QC, Yu ZH, Li JC, Cheng ZB, Chen L, Hu X, Chen YY, Wang J, et al. Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer. Radiother Oncol. 2015;114(2):161–6.PubMedCrossRef
20.
Honglian M, Zhouguang H, Fang P, Lujun Z, Dongming L, Yujin X, Yong B, Liming X, Yirui Z, Xiao H, et al. Different administration routes of recombinant human endostatin combined with concurrent chemoradiotherapy might lead to different efficacy and safety profile in unresectable stage III non-small cell lung cancer: Updated follow-up results from two phase II trials. Thorac Cancer. 2020;11(4):898–906.PubMedPubMedCentralCrossRef
21.
Bernchou U, Christiansen RL, Asmussen JT, Schytte T, Hansen O, Brink C. Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer. Radiother Oncol. 2017;123(1):93–8.PubMedCrossRef
22.
Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16(2):187–99.PubMedPubMedCentralCrossRef
23.
Tsujino Kayoko, Hashimoto Tomohisa, Shimada Temiko, Yoden Eisaku, Fujii Osamu, Ota Yosuke, Satouchi Miyako, Negoro Shunichi, Adachi Shuji. Soejima T: Combined analysis of V20, VS5, pulmonary fibrosis score on baseline computed tomography, and patient age improves prediction of severe radiation pneumonitis after concurrent chemoradiotherapy for locally advanced non-small-cell lung cancer. J Thorac Oncol. 2014;9(7):983–90.PubMedCrossRef
24.
Wu K, Xu X, Li X, Wang J, Zhu L, Chen X, Wang B, Zhang M, Xia B, Ma S. Radiation pneumonitis in lung cancer treated with volumetric modulated arc therapy. J Thorac Dis. 2018;10(12):6531–9.PubMedPubMedCentralCrossRef
25.
Jun D, Guang L, Lianghua M, Rao D, Shuang Z, Chong H, Shuo Z, Lei Y. Predictors of grade ≥ 2 and grade ≥ 3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy. Acta Oncol. 2012;52(6):1175–80.
26.
Dang J, Li G, Zang S, Zhang S, Yao L. Comparison of risk and predictors for early radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with radiotherapy with or without surgery. Lung Cancer. 2014;86(3):329–33.PubMedCrossRef
27.
Jang JY, Kim SS, Song SY, Kim YJ, Kim SW, Choi EK. Radiation pneumonitis in patients with non-small-cell lung cancer receiving chemoradiotherapy and an immune checkpoint inhibitor: a retrospective study. Radiat Oncol. 2021;16(1):231.PubMedPubMedCentralCrossRef
28.
Meng Y, Luo W, Wang W, Zhou C, Zhou S, Tang X, Hou L, Kong FS, Yang H. Intermediate Dose-Volume Parameters, Not Low-Dose Bath, Is Superior to Predict Radiation Pneumonitis for Lung Cancer Treated With Intensity-Modulated Radiotherapy. Front Oncol. 2020;10:584756.PubMedPubMedCentralCrossRef
29.
Tannehill SP, Mehta MP, Larson M, Storer B, Pellet J, Kinsella TJ, Schiller JH. Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: results of a phase II trial. J Clin Oncol. 1997;15(8):2850–7.PubMedCrossRef
30.
Calabro-Jones P, Fahey R, Smoluk G, Ward J. Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79–171 cells incubated in medium containing WR-2721. Int J Radiat Biol Relat Stud Phys Chem Med. 1985;47(1):23–7.PubMedCrossRef
31.
Antonadou, Coliarakis N, Synodinou M, Athanassiou H, Kouveli CV, Georgakopoulos G, Panoussaki K, Karageorgis P, Throuvalas N. Group CROH Randomized phase III trial of radiation treatment amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys. 2001;51(4):915–22.PubMedCrossRef
32.
Bourhis J, Blanchard P, Maillard E, Brizel DM, Movsas B, Buentzel J, Langendijk JA, Komaki R, Swan Leong S, Levendag P, et al. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol. 2011;29(18):2590–7.PubMedCrossRef
33.
Devine A, Marignol L. Potential of Amifostine for Chemoradiotherapy and Radiotherapy-associated Toxicity Reduction in Advanced NSCLC: A Meta-Analysis. Anticancer Res. 2016;36(1):5–12.PubMed
34.
Komaki R, Lee JS, Milas L, Lee HK, Fossella FV, Herbst RS, Allen PK, Liao Z, Stevens CW, Lu C, et al. Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial. Int J Radiat Oncol Biol Phys. 2004;58(5):1369–77.PubMedCrossRef
35.
Komaki R, Lee JS, Kaplan B, Allen P, Kelly JF, Liao Z, Stevens CW, Fossella FV, Zinner R, Papadimitrakopoulou V, et al. Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results. Semin Radiat Oncol. 2002;12(1 Suppl 1):46–9.PubMed
36.
Antonadou D, Throuvalas N, Petridis A, Bolanos N, Sagriotis A, Synodinou M. Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non–small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2003;57(2):402–8.PubMedCrossRef
37.
Jackson IL, Chen L, Batinic-Haberle I, Vujaskovic Z. Superoxide dismutase mimetic reduces hypoxia-induced O2*-, TGF-beta, and VEGF production by macrophages. Free Radic Res. 2007;41(1):8–14.PubMedCrossRef
38.
Tanabe K, Maeshima Y, Ichinose K, Kitayama H, Takazawa Y, Hirokoshi K, Kinomura M, Sugiyama H, Makino H. Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model. Kidney Int. 2007;71(3):227–38.PubMedCrossRef
39.
Zhang K, Yang S, Zhu Y, Mo A, Zhang D, Liu L. Protection against acute radiation-induced lung injury: a novel role for the anti-angiogenic agent Endostar. Mol Med Rep. 2012;6(2):309–15.PubMedCrossRef
40.
Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A. 2012;109(43):17561–6.ADSPubMedPubMedCentralCrossRef
41.
Zheng YF, Ge W, Xu HL, Cao DD, Liu L, Ming PP, Li CH, Xu XM, Tao WP, Tao ZZ. Endostar enhances the antitumor effects of radiation by affecting energy metabolism and alleviating the tumor microenvironment in a Lewis lung carcinoma mouse model. Oncol Lett. 2015;10(5):3067–72.PubMedPubMedCentralCrossRef
42.
Wu L, Pu X, Chen B, Wang Q, Liu L, Li K, Kong Y, Xu F, Li J, Xu L, et al. P40.14 Efficacy and Safety of Endostar Combined With Camrelizumab and Chemotherapy in Treatment of Advanced NSCLC A Multi-Center Retrospective Study. J Thorac Oncol. 2021;16(10):S1075–6.CrossRef
43.
Wu L, Pu XX, Chen LB, Wang ZQ, Liu YL, Li K, et al. EP08.01-095 efficacy and safety of combining Endostar with Camrelizumab plus chemotherapy in advanced NSCLC patients: a multi-center retrospective study. J Thorac Oncol. 2022;17(9):S388.
44.
Lv W, Pei X, Zhao W, Cong Y, Wei Y, Li T, Zhang H, Lin Z, Saito Y, Kim JJ, et al. Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer. Translational Lung Cancer Research. 2022;11(2):201–12.PubMedPubMedCentralCrossRef
45.
Yang Y, Li L, Jiang Z, Wang B, Pan Z. Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer. Cancer Immunol Immunother. 2020;69(12):2523–32.PubMedCrossRef
46.
Wu J, Zhao X, Sun Q, Jiang Y, Zhang W, Luo J, Li Y. Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model. Biomed Pharmacother. 2020;125:109746.PubMedCrossRef
47.
Zhao S, Ren S, Jiang T, Zhu B, Li X, Zhao C, Jia Y, Shi J, Zhang L, Liu X, et al. Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer. Cancer Immunol Res. 2019;7(4):630–43.PubMedCrossRef
48.
Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C, Qian J, Zhang Y, Chang Q, Zhang X, et al. Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021;16(4):643–52.PubMedCrossRef
49.
Zhou C, Wang Y, Zhao J, Chen G, Liu Z, Gu K, Huang M, He J, Chen J, Ma Z, et al. Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy. Clin Cancer Res. 2021;27(5):1296–304.PubMedCrossRef
50.
Taylor MH, Lee CH, Makker V, Rasco D, Dutcus CE, Wu J, Stepan DE, Shumaker RC, Motzer RJ. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J Clin Oncol. 2020;38(11):1154–63.PubMedPubMedCentralCrossRef
51.
Herbst RS, Arkenau H-T, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, et al. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. Lancet Oncol. 2019;20(8):1109–23.PubMedCrossRef
52.
Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–301.PubMedCrossRef
Metadata
Title
Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy
Authors
Kuifei Chen
Shuling Li
Meng Chen
Zhicheng Jin
Xuefeng Sun
Suna Zhou
Haihua Yang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12001-6

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Research

Impact of the COVID-19 pandemic in childhood and adolescent cancer care in northern Tanzania: a cross-sectional study

Research

Analysis of the efficacy of upfront brain radiotherapy versus deferred radiotherapy for EGFR/ALK-positive non-small cell lung cancer with brain metastases: a retrospective study

Research

Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration

Research

Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population

Study Protocol

A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR)

Research

RACGAP1 promotes the progression and poor prognosis of lung adenocarcinoma through its effects on the cell cycle and tumor stemness
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits