Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the ...Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the underlying molecular mechanisms.Methods:A subcutaneous xenograft model of Hep3B-derived HCC was established in nude mice,which were randomly divided into 2 groups(n=5 males per group):(1)intragastric administration of anlotinib(0.4 mg/kg)and(2)intragastric administration of normal saline.We constructed lenvatinib-resistant cell lines and randomly divided the mice into 3 groups(n=5 males per group):(1)intragastric administration of anlotinib,(2)intragastric administration of lenvatinib,and(3)intragastric administration of normal saline.After 2 weeks of treatment,tumor tissues were harvested,and mRNA and proteins were isolated from the tissues.Changes in the expression of cancer stemness markers(epithelial cell adhesion molecule[EpCAM],CD13,CD90,aldehyde dehydrogenase 1[ALDH1],CD44,and CD45),totipotency factors(sex-determining region Y-box 2[Sox2],Nanog,octamer-binding transcription factor 4[Oct4]),and genes related to the Notch signaling pathway were examined.Results:Compared with that in the control group,tumor size and weight were reduced in nude mice treated with anlotinib.These differences were statistically significant in both the types of nude mice.Anlotinib affected stemness markers and totipotency factors by downregulating the expression of CD133,CD90,and G-protein–coupled receptor 5(LGR5)and upregulating the expression of intercellular adhesion molecule 1(ICAM-1)and Sox2.In addition,lenvatinib-resistant cell lines increased Notch signaling pathway,whereas anlotinib inhibited Notch signaling pathway.Conclusions:The antitumor effect of anlotinib on HCC and lenvatinib-resistant HCC cellsmay occur through inhibition of the Notch signaling pathway.Anlotinib may be the drug of choice for sequential therapy in lenvatinib-resistant liver cancer.展开更多
Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with adv...Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.展开更多
Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoper...Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors.Methods:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October 2020.The primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and safety.Results:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,respectively.There was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,respectively.In the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.展开更多
BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we rep...BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we report a case involving the discovery of a pancreatic mass detected during a routine physical examination.Subsequent imaging and pathological tests of the patient led to the diagnosis of LGMS of the pancreas.Following surgical intervention,the patient experienced recurrence and metastasis.Conventional treatment is not effective for postoperative recurrent pancreatic LGMS with multiple metastases.After communicating with the patients and their families,informed consent was obtained for the treatment of anlotinib combined with pembrolizumab.Evaluation of imaging and clinical symptoms post-treatment revealed a relatively favorable response to the combination of anlotinib and pembrolizumab.CONCLUSION Based on the comprehensive literature review,our report aimed to provide evidence for a better understanding of the disease characteristics,diagnostic criteria,imaging findings,and identification of LGMS.And explore novel treatment strategies for this disease.展开更多
BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the ...BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.METHODS During the period spanning from April 2019 to April 2022,Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study,the observation group and the control group.The control group was administered anlotinib hy-drochloride as their designated therapy,whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group.The administration of treatment occurred in cycles consisting of a duration of 3 wk,and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups.A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period.Changes in the levels of carcinoembryonic Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy.Finally,a 1-year follow-up was conducted for both groups of patients,and the survival status was recorded and analyzed.RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group,with a statistically significant discrepancy(76.09%vs 50.00%),reaching a significance level denoted as P<0.05.Following the administration of treatment,the observation group manifested a considerable reduction in numerous serum indicators,which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group(P<0.05).Post-treatment,the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration,surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group(P<0.05).Subsequent to the therapeutic intervention,the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality.These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group(P<0.05).The safety levels of drug use in the two group were comparable(19.57%vs 13.04%),and no distinct difference was observed upon comparison(P>0.05).After the completion of treatment,both groups of patients underwent a 1-year follow-up outside the hospital.Throughout this period,1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up.During the follow-up period of the observation group,12 patients died,resulting in a survival rate of 73.33%(33/45),while in the control group,21 patients died,resulting in a survival rate of 52.27%(23/44).The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups(log-rank=4.710,P=0.030).CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients,leading to improvements in patient immunity and prognosis.Additionally,it exerted inhibitory effects on the expression of carcinoembryonic antigen,CA199,and CA125.展开更多
BACKGROUND Papillary thyroid cancer(PTC)is one of the well-differentiated thyroid tumors.Cutaneous metastasis from differentiated thyroid cancers occurs in<1%of primary thyroid carcinomas but produces the worst sur...BACKGROUND Papillary thyroid cancer(PTC)is one of the well-differentiated thyroid tumors.Cutaneous metastasis from differentiated thyroid cancers occurs in<1%of primary thyroid carcinomas but produces the worst survival prognosis.The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China.CASE SUMMARY In a patient with scalp metastasis caused by PTC,thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles.Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy.CONCLUSION The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.展开更多
BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for ...BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.展开更多
Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods t...Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods to explore the mechanism of multi-target and multi-pathway treatment of non-small cell lung cancer.Methods:The 3D molecular structure formula of anlotinib was obtained by searching the PubChem database,and the target of anlotinib was predicted by using the PharmMapper database;obtain non-small cell lung cancer related targets through the GeneCards database,screen common genes related to drug targets and diseases by Venny 2.1.0,and build the relationship between drugs and diseases.Through the STRING11.5 database,the interaction relationship between action targets was built,the protein-protein interaction network was constructed,and the target degree was analyzed by Cytocsape 3.7.2 software to screen molecular docking objects.The DAVID database was used for Gene Ontology gene enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis to predict its mechanism,and the AutoDock software was used for molecular docking of the main targets.Results:The analysis results showed that there were 76 possible targets involved in the treatment of non-small cell lung cancer with anlotinib,mainly acting on epidermal growth factor receptor,mitogen-activated protein kinase 14,tyrosine-protein phosphatase non-receptor type 11,heat shock protein HSP 90-alpha,tyrosine-protein kinase Lck,cAMP-dependent protein kinase catalytic subunit alpha and other target protein genes,Kyoto Encyclopedia of Genes and Genomes pathway analysis obtained 60 possible pathways related to its treatment of non-small cell lung cancer,mainly involving progesterone-mediated oocyte maturation,prostate cancer,proteoglycans in cancer,FoxO signaling pathway,pathways in cancer,Ras signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Anlotinib has the characteristics of multi-targets and multi-pathways in the treatment of non-small cell lung cancer,which provides a scientific basis for the follow-up study on the optimization of its efficacy in the treatment of non-small cell lung cancer and the revelation of the pharmacological effects of anlotinib.展开更多
Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and...Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.展开更多
Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HE...Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.展开更多
Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapie...Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)展开更多
Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line tre...Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line treatment agent in non-oncogene driven non-small cell lung cancer(NSCLC).This prospective study aimed to investigate the efficacy and safety of anlotinib plus S-1 for third-or later-line treatment in patients with advanced NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC,and documented disease progression following second-line chemotherapy,and/or epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)treatment were enrolled in this study.The patients were treated anlotinib(8 mg daily d 1–14)and S-1(60 mg/m^2 d 1–14)and the treatment was repeated every 3 weeks.Treatment was continued until disease progression or unacceptable toxicity occurred.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and adverse events(AEs)were reviewed and evaluated.Results Forty-one patients were enrolled in the study between June 2018 and December 2018.The total ORR and DCR were 26.8%and 80.5%,respectively.The median PFS was 5.2 months[95%confidence interval(CI),3.9 to 6.6 months].In the univariate analysis,there was a significant difference in the median PFS between patients with brain metastases and those without brain metastases(4.8 months vs 5.9 months,respectively;P=0.039).The Eastern Cooperative Oncology Group(ECOG)performance status(P=0.002),lines of therapy(P=0.015),and therapeutic evaluation(P=0.014)were independent factors that influenced PFS.The most common AEs were hypertension,proteinuria,myelosuppression,gastrointestinal reactions,fatigue,and mucositis.Conclusion Anlotinib plus S-1 is an effective and safe regimen for advanced NSCLC as third-or later-line therapy.展开更多
BACKGROUND Occult breast cancer(OBC)is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast.Due to its low incidence and unique clinical manifest...BACKGROUND Occult breast cancer(OBC)is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast.Due to its low incidence and unique clinical manifestations,there is a lack of consensus on the diagnosis and treatment of OBC.We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib.The treatment was well tolerated,and the patient achieved a pathologic complete response.CASE SUMMARY A 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast.Pathological biopsy confirmed right axillary metastatic carcinoma.Immunohistochemical staining results were positive for progesterone receptor,cytokeratin 7,specific breast markers GATA3 and gross cystic disease fluid protein-15.Tumor cells were negative for estrogen receptor,human epidermal growth factor receptor-2,cytokeratin 5/6,cytokeratin 20,and villin.The patient was diagnosed with OBC,and she underwent neoadjuvant chemotherapy combined with anlotinib.Mastectomy plus axillary lymph node dissection was performed.The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes.Postoperatively,she received adjuvant radiotherapy and endocrine therapy.CONCLUSION Neoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.展开更多
Objective:In the phase II ALTER-1202(NCT03059797)trial,anlotinib significantly improved progression-free survival(PFS)and overall survival(OS)in patients with advanced small-cell lung cancer(SCLC)who underwent at leas...Objective:In the phase II ALTER-1202(NCT03059797)trial,anlotinib significantly improved progression-free survival(PFS)and overall survival(OS)in patients with advanced small-cell lung cancer(SCLC)who underwent at least 2 previous chemotherapy cycles,when compared with a placebo group.To identify potential factors for predicting efficacy and prognosis with anlotinib treatment,we analyzed hematological indices at baseline and adverse events(AEs)over the course of anlotinib treatment.Methods:Data were collected from March 2017 to April 2019 from a randomized,double-blind,placebo-controlled,multicenter,phase II trial of anlotinib.Eligible patients were randomly assigned 2:1 to receive anlotinib or placebo until disease progression,intolerable toxicity,or withdrawal of consent.The patients received anlotinib(12 mg)or an analogue capsule(placebo)orally once daily for 14 days every 3 weeks.The hematological indices at baseline and AEs that occurred in the initial 2 treatment cycles were recorded.The Kaplan-Meier test and Cox regression model were used to assess survival differences.Results:A total of 82 patients(81 patients with complete data)were randomly assigned to receive anlotinib,with 38 receiving a placebo as a control.Multivariate analysis indicated that an elevated neutrophil to lymphocyte ratio>7.75 and lactate dehydrogenase>254.65 U/L at baseline were independent risk factors for PFS;basal elevated aspartate aminotransferase>26.75 U/L,neuron specific enolase>18.64 ng/mL,and fibrinogen>4.645 g/L were independent risk factors for OS.During treatment,elevatedγglutamyltransferase and hypophosphatemia were independent predictors for a poor PFS,and elevatedγ-glutamyl transferase and hypercholesterolemia were independent factors for OS.Conclusions:Our study preliminarily defined potential factors that affected the PFS and OS at baseline and during anlotinib treatment in patients with advanced SCLC.Our findings provide a basis for screening the dominant population and for dynamic efficacy monitoring with anlotinib therapy.展开更多
Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)w...Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)with locally advanced or metastatic soft tissue sarcoma were eligible.Each treatment cycle lasted for 3 weeks,and included liposomal doxorubicin(40-50 mg/m^(2))on day 1 and anlotinib(12 mg)on days 8-21.Starting from the 9th cycle,treatment consisted of only anlotinib.Treatment continued until disease progression or intolerable toxicities.The primary efficacy end point was progression-free survival(PFS).Results:Eight patients were enrolled between July 25,2019 and January 8,2020.The median number of treatment cycles was 5.5.Within 5.9 months median follow-up,PFS events occurred in 4(4/8,50%)patients.The median PFS was 11.3 months and the 6-month PFS rate was 56%.No patients attained complete response and 2 patients(fibrosarcoma,1 patient and undifferentiated pleomorphic sarcoma,1 patient)achieved partial response.Three patients(fibrosarcoma,2 patients and synovial sarcoma,1 patient)had stable disease.The objective response rate was 25%(2/8)for the study population,and the disease control rate was 75%(6/8).No new safety concerns emerged.Conclusions:Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas.Due to the small sample size,further investigations with a larger population should be undertaken to confirm the study findings.展开更多
Objective:In this post-hoc analysis,we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma(ESCC)patients.Methods:A total of 109 patient...Objective:In this post-hoc analysis,we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma(ESCC)patients.Methods:A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included.The tumor response was assessed by computed tomography at week 3,week 6,and then every 6 weeks until progressive disease was observed.The primary endpoint of the study was progression free survival(PFS).The secondary endpoints included overall survival(OS)and objective response rate(ORR).Results:In all patients,the median PFS was 3.02 months[95%confidence interval(CI):2.63–3.65 months]and the OS was 6.11 months(95%CI:4.40–7.79 months).The ORR was 7.34%(95%CI:3.22%–13.95%).A total of 59(54%)patients were diagnosed with treatment-induced hypertension(Group A),and the remaining patients(n=50,46%)were in Group B.Baseline prognostic factors were similar between the 2 groups.Patients in Group A had a longer PFS and OS and higher ORR.When stratifying patients using a previously known history of hypertension,treatment-induced hypertension was a predictor only for patients without previous hypertension,who had longer PFS[hazard ratio(HR):0.40,95%CI:0.24–0.68]and OS(HR:0.37,95%CI:0.21–0.67).Conclusions:We showed,for the first time,a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib,without a previously known history of hypertension.Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients,which may also reflect the intended target inhibition.展开更多
BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE S...BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE SUMMARY We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes.She underwent craniotomy,and the mass was resected.Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80%of tumor cells.Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53.At 1.5 mo after surgery,head magnetic resonance imaging revealed that the tumor had recurred.The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy.The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle.Following this regimen,the patient achieved stable disease for>17 mo.Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed.CONCLUSION This is the first reported case of SFT of the central nervous system treated with surgery,radiotherapy and anlotinib.This regimen may be an effective treatment option for malignant intracranial SFT patients.展开更多
The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabin...The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabine plus tegafur with best response of partial response.Second-line treatment was 4 cycles of nab-paclitaxel monotherapy ended up with disease progression.Third-line treatment was sintilimab with anlotinib for 10 cycles.The patient's condition has achieved clinical complete remission so far.展开更多
Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a po...Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes.We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA(ctDNA)next-generation sequencing.Statistical analysis showed that 6(24.0%)patients experienced prostate-specific antigen(PSA)response and 11(44.0%)patients experienced PSA reduction.The relationship between ctDNA findings and outcomes was also analyzed.DNA-damage repair(DDR)pathways and homologous recombination repair(HRR)pathway defects indicated a comparatively longer PSA-progressionfree survival(PSA-PFS;2.5 months vs 1.2 months,P=0.027;3.3 months vs 1.2 months,P=0.017;respectively).This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC.PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.展开更多
基金supported by the Natural Science Foundation of the Hubei Province(no.2023 AFB894)Open for the Key Laboratory of Biological Targeted Therapy in 2021(no.2021swbx019).
文摘Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the underlying molecular mechanisms.Methods:A subcutaneous xenograft model of Hep3B-derived HCC was established in nude mice,which were randomly divided into 2 groups(n=5 males per group):(1)intragastric administration of anlotinib(0.4 mg/kg)and(2)intragastric administration of normal saline.We constructed lenvatinib-resistant cell lines and randomly divided the mice into 3 groups(n=5 males per group):(1)intragastric administration of anlotinib,(2)intragastric administration of lenvatinib,and(3)intragastric administration of normal saline.After 2 weeks of treatment,tumor tissues were harvested,and mRNA and proteins were isolated from the tissues.Changes in the expression of cancer stemness markers(epithelial cell adhesion molecule[EpCAM],CD13,CD90,aldehyde dehydrogenase 1[ALDH1],CD44,and CD45),totipotency factors(sex-determining region Y-box 2[Sox2],Nanog,octamer-binding transcription factor 4[Oct4]),and genes related to the Notch signaling pathway were examined.Results:Compared with that in the control group,tumor size and weight were reduced in nude mice treated with anlotinib.These differences were statistically significant in both the types of nude mice.Anlotinib affected stemness markers and totipotency factors by downregulating the expression of CD133,CD90,and G-protein–coupled receptor 5(LGR5)and upregulating the expression of intercellular adhesion molecule 1(ICAM-1)and Sox2.In addition,lenvatinib-resistant cell lines increased Notch signaling pathway,whereas anlotinib inhibited Notch signaling pathway.Conclusions:The antitumor effect of anlotinib on HCC and lenvatinib-resistant HCC cellsmay occur through inhibition of the Notch signaling pathway.Anlotinib may be the drug of choice for sequential therapy in lenvatinib-resistant liver cancer.
基金Key R&D Program of Yan’an Municipal Bureau of Science and Technology(Project No.2021YF-21)。
文摘Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.
基金supported by Key Program,National Natural Science Foundation of China(No.81930016)Natural Science Foundation of Zhejiang Province(No.LY22H160046)Key Research&Development Plan of Zhejiang Province(No.2019C03050)。
文摘Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors.Methods:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October 2020.The primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and safety.Results:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,respectively.There was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,respectively.In the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.
文摘BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we report a case involving the discovery of a pancreatic mass detected during a routine physical examination.Subsequent imaging and pathological tests of the patient led to the diagnosis of LGMS of the pancreas.Following surgical intervention,the patient experienced recurrence and metastasis.Conventional treatment is not effective for postoperative recurrent pancreatic LGMS with multiple metastases.After communicating with the patients and their families,informed consent was obtained for the treatment of anlotinib combined with pembrolizumab.Evaluation of imaging and clinical symptoms post-treatment revealed a relatively favorable response to the combination of anlotinib and pembrolizumab.CONCLUSION Based on the comprehensive literature review,our report aimed to provide evidence for a better understanding of the disease characteristics,diagnostic criteria,imaging findings,and identification of LGMS.And explore novel treatment strategies for this disease.
文摘BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.METHODS During the period spanning from April 2019 to April 2022,Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study,the observation group and the control group.The control group was administered anlotinib hy-drochloride as their designated therapy,whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group.The administration of treatment occurred in cycles consisting of a duration of 3 wk,and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups.A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period.Changes in the levels of carcinoembryonic Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy.Finally,a 1-year follow-up was conducted for both groups of patients,and the survival status was recorded and analyzed.RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group,with a statistically significant discrepancy(76.09%vs 50.00%),reaching a significance level denoted as P<0.05.Following the administration of treatment,the observation group manifested a considerable reduction in numerous serum indicators,which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group(P<0.05).Post-treatment,the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration,surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group(P<0.05).Subsequent to the therapeutic intervention,the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality.These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group(P<0.05).The safety levels of drug use in the two group were comparable(19.57%vs 13.04%),and no distinct difference was observed upon comparison(P>0.05).After the completion of treatment,both groups of patients underwent a 1-year follow-up outside the hospital.Throughout this period,1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up.During the follow-up period of the observation group,12 patients died,resulting in a survival rate of 73.33%(33/45),while in the control group,21 patients died,resulting in a survival rate of 52.27%(23/44).The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups(log-rank=4.710,P=0.030).CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients,leading to improvements in patient immunity and prognosis.Additionally,it exerted inhibitory effects on the expression of carcinoembryonic antigen,CA199,and CA125.
文摘BACKGROUND Papillary thyroid cancer(PTC)is one of the well-differentiated thyroid tumors.Cutaneous metastasis from differentiated thyroid cancers occurs in<1%of primary thyroid carcinomas but produces the worst survival prognosis.The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China.CASE SUMMARY In a patient with scalp metastasis caused by PTC,thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles.Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy.CONCLUSION The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.
文摘BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.
基金This research was supported by Innovation and Entrepreneurship Training Plan for College Students in Jiangsu Province(202112688022Y)Suzhou Science and Technology Bureau Minsheng Science and Technology Medical and Health Application Basic Research Project(SYSD2019082).
文摘Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods to explore the mechanism of multi-target and multi-pathway treatment of non-small cell lung cancer.Methods:The 3D molecular structure formula of anlotinib was obtained by searching the PubChem database,and the target of anlotinib was predicted by using the PharmMapper database;obtain non-small cell lung cancer related targets through the GeneCards database,screen common genes related to drug targets and diseases by Venny 2.1.0,and build the relationship between drugs and diseases.Through the STRING11.5 database,the interaction relationship between action targets was built,the protein-protein interaction network was constructed,and the target degree was analyzed by Cytocsape 3.7.2 software to screen molecular docking objects.The DAVID database was used for Gene Ontology gene enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis to predict its mechanism,and the AutoDock software was used for molecular docking of the main targets.Results:The analysis results showed that there were 76 possible targets involved in the treatment of non-small cell lung cancer with anlotinib,mainly acting on epidermal growth factor receptor,mitogen-activated protein kinase 14,tyrosine-protein phosphatase non-receptor type 11,heat shock protein HSP 90-alpha,tyrosine-protein kinase Lck,cAMP-dependent protein kinase catalytic subunit alpha and other target protein genes,Kyoto Encyclopedia of Genes and Genomes pathway analysis obtained 60 possible pathways related to its treatment of non-small cell lung cancer,mainly involving progesterone-mediated oocyte maturation,prostate cancer,proteoglycans in cancer,FoxO signaling pathway,pathways in cancer,Ras signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Anlotinib has the characteristics of multi-targets and multi-pathways in the treatment of non-small cell lung cancer,which provides a scientific basis for the follow-up study on the optimization of its efficacy in the treatment of non-small cell lung cancer and the revelation of the pharmacological effects of anlotinib.
文摘Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.
基金supported by the National Natural Science Foundation of China(Grant No.81672634)National Key Research and Development Program of China(Grant No.2018YFC0115204)+2 种基金Capital Health Development Scientific Research Project(Grant No.2018-2-4023)Clinical Translation and Medical Research Fund of Chinese Academy of Medical Sciences(Grant No.12019XK320071)Peking Union Medical College Graduate Innovation Fund(Grant No.2018-1002-02-25)。
文摘Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81802296)Natural Science Foundation of Tianjin(Grant No.18JCQNJC82500)Tianjin Municipality Science and Technology Commission Projects(Grant No.12ZCDZSY15600).
文摘Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)
基金Supported by a grant from the Youth National Science Foundation of China(No.61702164)。
文摘Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line treatment agent in non-oncogene driven non-small cell lung cancer(NSCLC).This prospective study aimed to investigate the efficacy and safety of anlotinib plus S-1 for third-or later-line treatment in patients with advanced NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC,and documented disease progression following second-line chemotherapy,and/or epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)treatment were enrolled in this study.The patients were treated anlotinib(8 mg daily d 1–14)and S-1(60 mg/m^2 d 1–14)and the treatment was repeated every 3 weeks.Treatment was continued until disease progression or unacceptable toxicity occurred.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and adverse events(AEs)were reviewed and evaluated.Results Forty-one patients were enrolled in the study between June 2018 and December 2018.The total ORR and DCR were 26.8%and 80.5%,respectively.The median PFS was 5.2 months[95%confidence interval(CI),3.9 to 6.6 months].In the univariate analysis,there was a significant difference in the median PFS between patients with brain metastases and those without brain metastases(4.8 months vs 5.9 months,respectively;P=0.039).The Eastern Cooperative Oncology Group(ECOG)performance status(P=0.002),lines of therapy(P=0.015),and therapeutic evaluation(P=0.014)were independent factors that influenced PFS.The most common AEs were hypertension,proteinuria,myelosuppression,gastrointestinal reactions,fatigue,and mucositis.Conclusion Anlotinib plus S-1 is an effective and safe regimen for advanced NSCLC as third-or later-line therapy.
基金Supported by Health Specific Program of Jilin Province,China,No.2018SCZWSZX-035Scientific and Technological Development Program of Jilin Province,China,No.20190701041GH.
文摘BACKGROUND Occult breast cancer(OBC)is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast.Due to its low incidence and unique clinical manifestations,there is a lack of consensus on the diagnosis and treatment of OBC.We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib.The treatment was well tolerated,and the patient achieved a pathologic complete response.CASE SUMMARY A 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast.Pathological biopsy confirmed right axillary metastatic carcinoma.Immunohistochemical staining results were positive for progesterone receptor,cytokeratin 7,specific breast markers GATA3 and gross cystic disease fluid protein-15.Tumor cells were negative for estrogen receptor,human epidermal growth factor receptor-2,cytokeratin 5/6,cytokeratin 20,and villin.The patient was diagnosed with OBC,and she underwent neoadjuvant chemotherapy combined with anlotinib.Mastectomy plus axillary lymph node dissection was performed.The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes.Postoperatively,she received adjuvant radiotherapy and endocrine therapy.CONCLUSION Neoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.
文摘Objective:In the phase II ALTER-1202(NCT03059797)trial,anlotinib significantly improved progression-free survival(PFS)and overall survival(OS)in patients with advanced small-cell lung cancer(SCLC)who underwent at least 2 previous chemotherapy cycles,when compared with a placebo group.To identify potential factors for predicting efficacy and prognosis with anlotinib treatment,we analyzed hematological indices at baseline and adverse events(AEs)over the course of anlotinib treatment.Methods:Data were collected from March 2017 to April 2019 from a randomized,double-blind,placebo-controlled,multicenter,phase II trial of anlotinib.Eligible patients were randomly assigned 2:1 to receive anlotinib or placebo until disease progression,intolerable toxicity,or withdrawal of consent.The patients received anlotinib(12 mg)or an analogue capsule(placebo)orally once daily for 14 days every 3 weeks.The hematological indices at baseline and AEs that occurred in the initial 2 treatment cycles were recorded.The Kaplan-Meier test and Cox regression model were used to assess survival differences.Results:A total of 82 patients(81 patients with complete data)were randomly assigned to receive anlotinib,with 38 receiving a placebo as a control.Multivariate analysis indicated that an elevated neutrophil to lymphocyte ratio>7.75 and lactate dehydrogenase>254.65 U/L at baseline were independent risk factors for PFS;basal elevated aspartate aminotransferase>26.75 U/L,neuron specific enolase>18.64 ng/mL,and fibrinogen>4.645 g/L were independent risk factors for OS.During treatment,elevatedγglutamyltransferase and hypophosphatemia were independent predictors for a poor PFS,and elevatedγ-glutamyl transferase and hypercholesterolemia were independent factors for OS.Conclusions:Our study preliminarily defined potential factors that affected the PFS and OS at baseline and during anlotinib treatment in patients with advanced SCLC.Our findings provide a basis for screening the dominant population and for dynamic efficacy monitoring with anlotinib therapy.
文摘Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)with locally advanced or metastatic soft tissue sarcoma were eligible.Each treatment cycle lasted for 3 weeks,and included liposomal doxorubicin(40-50 mg/m^(2))on day 1 and anlotinib(12 mg)on days 8-21.Starting from the 9th cycle,treatment consisted of only anlotinib.Treatment continued until disease progression or intolerable toxicities.The primary efficacy end point was progression-free survival(PFS).Results:Eight patients were enrolled between July 25,2019 and January 8,2020.The median number of treatment cycles was 5.5.Within 5.9 months median follow-up,PFS events occurred in 4(4/8,50%)patients.The median PFS was 11.3 months and the 6-month PFS rate was 56%.No patients attained complete response and 2 patients(fibrosarcoma,1 patient and undifferentiated pleomorphic sarcoma,1 patient)achieved partial response.Three patients(fibrosarcoma,2 patients and synovial sarcoma,1 patient)had stable disease.The objective response rate was 25%(2/8)for the study population,and the disease control rate was 75%(6/8).No new safety concerns emerged.Conclusions:Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas.Due to the small sample size,further investigations with a larger population should be undertaken to confirm the study findings.
基金funded by the Chia Tai Tianqing Pharmaceutical Group Co,Ltd.
文摘Objective:In this post-hoc analysis,we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma(ESCC)patients.Methods:A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included.The tumor response was assessed by computed tomography at week 3,week 6,and then every 6 weeks until progressive disease was observed.The primary endpoint of the study was progression free survival(PFS).The secondary endpoints included overall survival(OS)and objective response rate(ORR).Results:In all patients,the median PFS was 3.02 months[95%confidence interval(CI):2.63–3.65 months]and the OS was 6.11 months(95%CI:4.40–7.79 months).The ORR was 7.34%(95%CI:3.22%–13.95%).A total of 59(54%)patients were diagnosed with treatment-induced hypertension(Group A),and the remaining patients(n=50,46%)were in Group B.Baseline prognostic factors were similar between the 2 groups.Patients in Group A had a longer PFS and OS and higher ORR.When stratifying patients using a previously known history of hypertension,treatment-induced hypertension was a predictor only for patients without previous hypertension,who had longer PFS[hazard ratio(HR):0.40,95%CI:0.24–0.68]and OS(HR:0.37,95%CI:0.21–0.67).Conclusions:We showed,for the first time,a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib,without a previously known history of hypertension.Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients,which may also reflect the intended target inhibition.
文摘BACKGROUND Solitary fibrous tumor(SFT)of the central nervous system is rare.It is predominantly benign and rarely malignant.There is no established standardized treatment regimen for malignant intracranial SFTs.CASE SUMMARY We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes.She underwent craniotomy,and the mass was resected.Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80%of tumor cells.Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53.At 1.5 mo after surgery,head magnetic resonance imaging revealed that the tumor had recurred.The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy.The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle.Following this regimen,the patient achieved stable disease for>17 mo.Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed.CONCLUSION This is the first reported case of SFT of the central nervous system treated with surgery,radiotherapy and anlotinib.This regimen may be an effective treatment option for malignant intracranial SFT patients.
文摘The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabine plus tegafur with best response of partial response.Second-line treatment was 4 cycles of nab-paclitaxel monotherapy ended up with disease progression.Third-line treatment was sintilimab with anlotinib for 10 cycles.The patient's condition has achieved clinical complete remission so far.
基金This study was supported by the State Key Science Infrastructure of Transitional Medicine,Shanghai Jiao Tong University(TMSK-2021-107)the Fostering Fund of Ren Ji Hospital(PYII20-02).
文摘Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes.We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA(ctDNA)next-generation sequencing.Statistical analysis showed that 6(24.0%)patients experienced prostate-specific antigen(PSA)response and 11(44.0%)patients experienced PSA reduction.The relationship between ctDNA findings and outcomes was also analyzed.DNA-damage repair(DDR)pathways and homologous recombination repair(HRR)pathway defects indicated a comparatively longer PSA-progressionfree survival(PSA-PFS;2.5 months vs 1.2 months,P=0.027;3.3 months vs 1.2 months,P=0.017;respectively).This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC.PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
