Anlotinib for the Treatment of Patients with Locally Advanced or Metastatic Medullary Thyroid Cancer

Sun, Yongkun; Du, Feng; Gao, Ming; Ji, Qinghai; Li, Zhendong; Zhang, Yuan; Z, Guo; Wang, Jun; Chen, Xiangjin; Wang, Jinwan; Chi, Yihebali; Tang, Ping-zhang

doi:10.1089/thy.2018.0022

Cited by 88 publications

(78 citation statements)

References 28 publications

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“…[12][13][14] Anlotinib has encouraging antitumor effects and acceptable toxicity in advanced lung adenocarcinoma, lung squamous cell carcinoma, STS, medullary thyroid cancer, small cell lung cancer and metastatic renal clear cell cancer. [15][16][17][18] A Phase II clinical trial showed that a total of 166 relapsed advanced STS patients had a significant survival benefit after treatment with anlotinib, with a 12-week progressionfree rate of 68.42% and an objective response rate of 12.65%. The PFS and OS were 5.63 and 12.33 months, respectively.…”

Section: Introductionmentioning

confidence: 99%

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

Wang

Chu

Zhang

et al. 2020

OTT

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Purpose: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. Patients and Methods: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. Results: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. Conclusion: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.

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Section: Introductionmentioning

confidence: 99%

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

Wang

Chu

Zhang

et al. 2020

OTT

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“…It is a novel multi-target TKI that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR a/b, c-Kit, and Ret. In so-doing, it effectively suppresses tumor angiogenesis and growth, with acceptable toxicity as seen in lu ng squamous cell carcinoma, advanced lung adenocarcinoma, small cell lung cancer, soft tissue sarcoma, medullary thyroid cancer, and metastatic renal clear cell cancer (Han et al, 2018;Sun et al, 2018;Shao et al, 2019;Yang et al, 2019;Zhou et al, 2019). Its major side effects include fatigue, high blood pressure, hand-foot skin reaction, gastrointestinal reactions, triglyceride elevation cholesterol elevation, and blood thyrotrophin elevation (Sun et al, 2016;Shao et al, 2019;Wang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Hypertensive Retinopathy Secondary to Anlotinib Treatment

Zhang

Xie

et al. 2020

Front. Pharmacol.

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Purpose: We report a case of a middle-aged woman who developed hypertensive retinopathy following oral administration of Anlotinib. Observations: A 48-year-old woman presented to our hospital with sudden painless loss of vision in both eyes combined with headache, nausea, and vomiting following oral administration of Anlotinib. This drug is often used to control cancer progression. Due to the deterioration of her blood pressure, which reached 167/113 mm Hg, Anlotinib was discontinued and the blood pressure was controlled by hypertension medications. This normalized her blood pressure, alleviated headache, and restored her vision. She visited our eye department 37 days later for eye checkup. The best-corrected visual acuities was 0.3 in the right eye and 0.4 in the left eye. The fundus examinations revealed a clear boundary of the optic papilla with significant stellate exudation in the macular area. The posterior pole of the retina displayed high hemorrhage, with a cotton-wool spot appearance. Optical coherence tomography (OCT) revealed atrophy in the outer segment of macular area, and hard exudations in retinal layers. Based on these findings, hypertensive retinopathy was diagnosed, as a secondary complication of Anlotinib. Conclusions and Significance: Anlotinib can induce hypertensive retinopathy. Patients receiving this drug should be closely monitored for potential complications.

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“…As a multitargeting tyrosine inhibitor in clinical development, Anlotinib exerts antitumor effects through anti-angiogenesis activity targeting multiple tyrosine kinases such as vascular endothelial growth factor receptor 1/2/3 (VEGFR-1/2/3), platelet-derived growth factor receptor (PDGFR) and broblast growth factor receptor (FGFR) [8]. It was reported that Anlotinib have signi cant antitumoral effect on solid tumor including thyroid cancer [9], non-small lung cancer [10], soft tissue sarcoma [11], renal cancer [12] and gastric cancer [13]. However, there is little research focusing on whether Anlotinib have an antitumor effect on oral squamous cell carcinoma which is one of the most common cancers in head and neck region.…”

Section: Discussionmentioning

confidence: 99%

Anlotininb as a Promising Inhibitor on Tumor Growth of Oral Squamous Cell Carcinoma Through Cell Apoptosis and Mitotic Catastrophe

Deng

Liao

Wei

et al. 2020

Preprint

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BackgroundOral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. ResultsHigher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p<0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. ConclusionAnlotinib could exert an antitumor effect on oral cancer cells lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.

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Anlotinib for the Treatment of Patients with Locally Advanced or Metastatic Medullary Thyroid Cancer

Abstract: Anlotinib demonstrated a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic MTC.

Cited by 88 publications

References 28 publications

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

Hypertensive Retinopathy Secondary to Anlotinib Treatment

Anlotininb as a Promising Inhibitor on Tumor Growth of Oral Squamous Cell Carcinoma Through Cell Apoptosis and Mitotic Catastrophe

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