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Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

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CHINESE JOURNAL OF INTEGRATIVE MEDICINE 2024年第7期30卷 643-652页

作者： Li, Rui Zhang, Tong Yan, Shao-hua Yan, Yun-zi Ding, Ya-cong Wang, Yan-song Yang, Yu-fei Xiyuan Hosp China Acad Chinese Med Sci Dept Oncol Beijing 100091 Peoples R China Beijing Univ Chinese Med Dept Oncol Dongfang Hosp Beijing 100078 Peoples R China Beijing Univ Chinese Med Grad Sch Beijing 100029 Peoples R China

ObjectiveTo assess the effectiveness of Chinese herbal medicine (CHM) combined with adjuvant Chemotherapy on myelosuppression for colorectal cancer (CRC) patients using network meta-analysis (NMA).MethodsLiterature searches in both international (PubMed, Embase, Web of Science, and Cochrane Library) and Chinese (China Science and Technology Journal Database, Wanfang Data, China National Knowledge Infrastructure) databases for relevant randomized controlled trials (RCTs) were conducted from inception until October 10, 2022. We included RCTs of patients who received CHM combined with Chemotherapy, including FOLFOX, XELOX, FOLFIRI, and other relevant regimens in the CHM treatment group. The outcomes included the incidence of myelosuppression, leukopenia, hemoglobin reduction, and thrombocytopenia. Two reviewers independently screened the databases, extracted the data, and assessed the risk of bias and credibility of evidence. RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA.ResultsA total of 31 RCTs were included, published from 2008 to 2021 in Chinese. Among these, 2,314 participants comparing the following 9 CHMs were identified: Shengbai Recipe (SBR), Bazhen Decoction (BZD), Jianpi Jiedu Recipe (JJR), Jianpi Recipe (JR), Compound Cantharis Capsule (CCC), Zaofan Pill (ZFP), Guilu Erxian Gel (GL), Buzhong Tiaogan Decoction (BZ), and Qiamagu Capsule (QM). The results of NMA found an indirect comparison. Based on the surface under the cumulative ranking curve (SUCRA), the ZFP+ Chemotherapy group had the lowest incidence of myelosuppression, with an odds ratio (OR) of 0.08 [95% confidence interval (CI): 0.01, 0.76], whereas the GL+ Chemotherapy group had the lowest incidence of leukopenia, hemoglobin reduction, and thrombocytopenia, with an OR of 5.25 (95% CI: 2.41, 11.43), 4.66 (95% CI: 2.23, 9.72), and 0.27 (95% CI: 0.13, 0.54), respectively. Moreover, BZD + Chemotherapy could alleviate leukopenia, hemoglobin reduction, and thrombocytopenia (P<0.01). Pairwise comparison showed that there was no diff

关键词： Chinese herbal medicine colorectal cancer network meta-analysis systematic review myelosuppression Chemotherapy III COLON-CANCER OXALIPLATIN FLUOROURACIL NEUTROPENIA MULTICENTER LEUCOVORIN ANEMIA TRENDS

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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus Chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

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Signal Transduction and Targeted Therapy 2024年第2期9卷 797-806页

作者： Yan Huang Yunpeng Yang Yuanyuan Zhao Hongyun Zhao Ningning Zhou Yaxiong Zhang Likun Chen Ting Zhou Gang Chen Ting Wu Lu Lu Shilin Xue Xiaoyan Kang Li Zhang Wenfeng Fang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineNo.651 Dongfeng East RoadGuangzhouGuangdong 510060China Department of Medicine Qilu Pharmaceutical Co.Ltd.JinanChina

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and Chemotherapy with or without bevacizumab in this population.Patients were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were enrolled.Most frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)patients.Twenty-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus Chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting.Moreover,QL1706 plus Chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.

关键词： bevacizumab Chemotherapy phase

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Measles,mumps,and rubella revaccination in children after completion of Chemotherapy and hematopoietic stem cell transplantation:a single-center prospective efficacy and safety analysis

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World Journal of Pediatrics 2023年第11期19卷 1062-1070页

作者： Min Wang Qing Yuan Peng-Fei Deng Yi Fei Hua Zhang Fen Zhou Wen-Juan Chen Qing Cao Jing Chen Yi-Jin Gao Department of Hematology and Oncology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityNo.1678 Dongfang RoadPudong DistrictShanghai200127China Center for Diseases Control and Prevention Fudan University Pudong Institute of Preventive MedicineShanghai200136China Department of Infectious Diseases Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghaiChina

Background Chemotherapy and hematopoietic stem cell transplantation(HSCT)can damage the immune system,and may result in a loss of protection from infectious diseases.This study aimed to evaluate the impact of these treatments on the decrease in antibody titers of the measles,mumps,and rubella(MMR)vaccine and seroconversion post-revaccination of MMR.Methods After completion of treatment for primary diseases,participants received an MMR revaccination.Antibody titers for MMR before revaccination were analyzed for all 110 children.After revaccination,68 participants received a follow-up evaluation of antibody titer and adverse reaction.Results Multivariable analysis showed that therapeutic schedules were the only factor correlated with lack of antibody titers for measles after completing treatment(P=0.008),while for mumps and rubella,no statistically significant difference was observed.Importantly,our study clearly demonstrated positive seroconversion rates for measles(97.5%),mumps(81.0%),and rubella(93.2%),with antibody levels rising across the board and peaking at around 6 months following revaccination.However,6 months after revaccination,a downtrend of antibody titer levels was observed,which is comparatively earlier than the waning immunity observed in healthy children.Furthermore,we found MMR revaccination to be safe,with only a single adverse reaction(local pain at the injection site)reported.Conclusions MMR revaccination is immunogenic for the population.We suggest periodic monitoring of antibody titers,in addition to a booster vaccination,although the optimal timing of booster vaccination remains to be investigated further.

关键词： Adjuvant Chemotherapy Children Hematopoietic stem cell transplantation Immunogenicity Mumps-measles-rubella.Vaccine

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Efficacy and clinical outcome of Chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer

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Chinese Medical Journal 2023年第12期136卷 1459-1467页

作者： Yang Yuan Shaohua Zhang Tao Wang Li Bian Min Yan Yongmei Yin Yuhua Song Yi Wen Jianbin Li Zefei Jiang Department of Oncology No.4 Ward The Fifth Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100071China Department of Oncology No.3 Ward The Fifth Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100071China Department of Breast Disease Henan Breast Cancer CenterThe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008 China Department of Breast Cancer Jiangsu Province Hospital&The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029 China Department of Breast Cancer Center The Affiliated Hospital of Qingdao UniversityQingdaoShandong 260000 China Medical Department Medpion(Beijing)Medical Technology Co.LtdBeijing 100062 China

Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while Chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

关键词： Breast neoplasms Metastatic breast cancer Hormone receptor-positive HER2-negative Chemotherapy Endocrine therapy First-line treatment Maintenance therapy

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Chemotherapy suppresses SHH gene expression via a specific enhancer

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Journal of Genetics and Genomics 2023年第1期50卷 27-37页

作者： Yafei Zhang Jianqiong Lin Kaibin Yang Zhicao Yue Department of Cell Biology and Medical Genetics International Cancer Centerand Guangdong Key Laboratory for Genome Stability and Disease PreventionShenzhen University Medical SchoolShenzhenGuangdong 518060China

Sonic hedgehog(SHH)signaling is a key regulator of embryonic development and tissue homeostasis that is involved in gastrointestinal(GI)cancer progression.Regulation of SHH gene expression is a paradigm of long-range enhancer function.Using the classical Chemotherapy drug 5-fluorouracil(5FU)as an example,here we show that SHH gene expression is suppressed by Chemotherapy.SHH is downstream of immediate early genes(IEGs),including Early growth response 1(Egr1).A specific 139 kb upstream enhancer is responsible for its down-regulation.Knocking down EGR1 expression or blocking its binding to this enhancer renders SHH unresponsive to Chemotherapy.We further demonstrate that down-regulation of SHH expression does not depend on 5FU’s impact on nucleotide metabolism or DNA damage;rather,a sustained oxidative stress response mediates this rapid suppression.This enhancer is present in a wide range of tumors and normal tissues,thus providing a target for cancer Chemotherapy and its adverse effects on normal tissues.We propose that SHH is a stress-responsive gene downstream of IEGs,and that traditional Chemotherapy targets a specific enhancer to suppress its expression.

关键词： Sonic hedgehog Chemotherapy Immediate early genes EGR1 5-Fluorouracil

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Construction of a novel six-gene signature to predict tumour response to induction Chemotherapy and overall survival in locoregionally advanced laryngeal and hypopharyngeal carcinoma

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Genes & Diseases 2024年第3期11卷 148-150页

作者： Chen Tan Lingwa Wang Yifan Yang Shizhi He George G.Chen Jason YK.Chan Michael CF.Tong C.A.van Hasselt Wenbin Xu Ling Feng Ru Wang Jugao Fang Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Key Laboratory of Otolaryngology Head and Neck Surgery(Ministry of Education of China) Beijing Institute of OtolaryngologyBeijing 100730China Department of Otorhinolaryngology Head and Neck SurgeryThe Chinese University of Hong KongPrince of Wales HospitalHongKong SAR999077China Department of Medical Genetics Institute of Basic Medical ScienceChinese Academy of Medical Science&Peking Union Medical CollageBeijing 100730China

Locoregionally advanced laryngeal and hypopharyngeal cancers(LA-LHCs)are traditionally treated with surgery followed by postoperative radiotherapy,which impairs speech and swallowing functions and reduces the quality of life.^(1,2)The use of induction Chemotherapy(IC)as a larynxpreserving approach for LA-LHCs has been verified and refined.^(3)However,the short-term tumor response to IC varies,non-responders usually show poor survival and little benefit.

关键词： Chemotherapy laryngeal surgery

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Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel Chemotherapy

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Asian Journal of Andrology 2023年第4期25卷 520-527页

作者： Jun-Hong Li Xing-Ming Zhang Xiao-Jie Bian Wei-Jie Gu Fang-Ning Wan Bo Dai Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Shanghai Genitourinary Cancer Institute Shanghai 200032China

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

关键词： adipocytokines body composition castration-resistant prostate cancer Chemotherapy prognosis

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Adjuvant Chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer:a randomized,non-inferiority,multicenter trial

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Frontiers of Medicine 2023年第1期17卷 93-104页

作者： Danhui Weng Huihua Xiong Changkun Zhu Xiaoyun Wan Yaxia Chen Xinyu Wang Youzhong Zhang Jie Jiang Xi Zhang Qinglei Gao Gang Chen Hui Xing Changyu Wang Kezhen Li Yaheng Chen Yuyan Mao Dongxiao Hu Zimin Pan Qingqin Chen Baoxia Cui Kun Song Cunjian Yi Guangcai Peng Xiaobing Han Ruifang An Liangsheng Fan Wei Wang Tingchuan Xiong Yile Chen Zhenzi Tang Lin Li Xingsheng Yang Xiaodong Cheng Weiguo Lu Hui Wang Beihua Kong Xing Xie Ding Ma Department of Obstetrics and Gynecology Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Oncology Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Gynecologic Oncology Women’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China Department of Obstetrics and Gynecology Qilu HospitalShandong UniversityJinan 250012China Department of Obstetrics and Gynecology Xiangyang Central HospitalHubei University of Arts and ScienceXiangyang 441021China Department of Obstetrics and Gynecology The First Affiliated Hospital of Yangtze UniversityJingmen 448000China Department of Obstetrics and Gynecology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Department of Obstetrics and Gynecology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Gynecologic Oncology Affiliated Tumour HospitalXinjiang Medical UniversityUrumqi 830000China Department of Gynecologic Oncology Hunan Province Tumor HospitalChangsha 410013China

We conducted a prospective study to assess the non-inferiority of adjuvant Chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB–IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant Chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant Chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant Chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415–1.757;P = 0.667) favoring adjuvant Chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The Chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant Chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant Chemotherapy alone is a favorable alternative post-operative treatment.

关键词： Chemotherapy cervical cancer lymph node metastasis concurrent chemoradiotherapy quality of life

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Cancer-cell-biomimetic nanoparticles systemically eliminate hypoxia tumors by synergistic Chemotherapy and checkpoint blockade immunotherapy

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2103-2119页

作者： Yongrong Yao Huachao Chen Ninghua Tan State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Checkpoint blockade-based immunotherapy has shown unprecedented effect in cancer treatments,but its clinical implementation has been restricted by the low host antitumor response rate.Recently,Chemotherapy is well recognized to activate the immune system during some chemotherapeutics-mediated tumor eradication.The enhancement of immune response during Chemotherapy might further improve the therapeutic efficiency through the synergetic mechanism.Herein,a synergistic antitumor platform(designated as BMS/RA@CC-Liposome)was constructed by utilizing CT26 cancer-cell-biomimetic nanoparticles that combined chemotherapeutic drug(RA-V)and PD-1/PD-L1 blockade inhibitor(BMS-202)to remarkably enhance antitumor immunity.In this study,the cyclopeptide RA-V as chemotherapeutic drugs directly killing tumor cells and BMS-202 as anti-PD agents eliciting antitumor immune responses were co-encapsulated in a pH-sensitive nanosystem.To achieve the cell-specific targeting drug delivery,the combination therapy nanosystem was functionalized with cancer cell membrane camouflage.The biomimetic drug delivery system perfectly disguised as endogenous substances,and realized elongated blood circulation due to anti-phagocytosis capability.Moreover,the BMS/RA@CC-Liposome also achieved the selective targeting of CT26 cells by taking advantage of the inherent homologous adhesion property of tumor cells.The in vitro and in vivo experiments revealed that the BMS/RA@CC-Liposome realized PD-1/PD-L1 blockade-induced immune response,RA-V-induced PD-L1 down-regulation and apoptosis in cancer cells.Such a system combining the advantages of Chemotherapy and checkpoint blockade-based immunotherapy to create an immunogenic tumor microenvironment systemically,demonstrated improved therapeutic efficacy against hypoxic tumor cells and offers an alternative strategy based on the immunology of the PD-1/PD-L1 pathway.

关键词： Checkpoint blockadebased immunotherapy Chemotherapy Synergetic mechanism Cancer-cell-biomimetic nanoparticles Cyclopeptide RA-V Antitumor immune response Combination therapy nanosystem PD-1/PD-L1 pathway

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Adding cyclosporin A to eltrombopag for aplastic anemia secondary to Chemotherapy for solid cancers

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Chinese Medical Journal 2023年第9期136卷 1120-1122页

作者： Ziqi Wan Yang Chen Junling Zhuang Miao Chen Shuyang Zhang Bing Han Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical ScienceBeijing 100730China Eight-Year Program of Clinical Medicine M.D.ProgramDepartment of Clinical MedicinePeking Union Medical CollegeBeijing 100005China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical ScienceBeijing 100730China

To the Editor:Myelosuppression is one of the most common side effects of Chemotherapy.Some patients would develop long-lasting aplastic anemia(AA)even after stopping Chemotherapy for over three months,due to persistent destruction of the bone marrow.As a thrombopoietin-receptor agonist,eltrombopag(EPAG)has been widely used in patients with thrombocytopenia from various origins,[1]including those with AA secondary to Chemotherapy.However,both EPAG and cyclosporin A(CsA)have been reported to possibly induce the expansion of abnormal clones or controversially increase the risk of neoplasms.[2]Thus,the challenge was to treat severe cytopenia while preventing cancer relapse.Our study reported the efficacy and safety of EPAG with or without CsA for patients with AA secondary to Chemotherapy,in an attempt to find solutions to these difficulties.

关键词： anemia Chemotherapy cyclosporin

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