Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma

Cancer Medicine

Wei‐Qi Lu¹  Han‐Xing Tong¹  Hua Yang¹  Yong Zhang¹  Xi Guo²  Zhi‐Ming Wang²  Rong‐Yuan Zhuang²  Yu‐Hong Zhou²  Shi‐Long Zhang³ 

[1] Department of General Surgery Shanghai Public Health Clinical Center Zhongshan Hospital (South Branch) Fudan University Shanghai China;Department of Medical Oncology Zhongshan Hospital Fudan University Shanghai China;Minhang Hospital Fudan University Shanghai China;

关键词: anlotinib;    combination;    epirubicin;    patient‐derived xenografts;    soft tissue sarcoma;    tyrosine kinase inhibitor;   

DOI  :  10.1002/cam4.2941

来源: DOAJ

【 摘 要 】

Abstract Background Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient‐derived xenografts (PDX) model. Methods We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty‐six PDX models were divided into six groups and treated with anlotinib alone (low‐dose, 1.5 or high‐dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150‐200 mm3. After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki‐67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. Results After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high‐dose anlotinib group was significantly smaller than the low‐dose anlotinib group (P < .001). Combined high‐dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib‐containing regimen, the expression levels of CD31, EGFR, MVD, and Ki‐67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity. Conclusions High‐dose anlotinib combined with epirubicin was an effective and safe therapy for STS.

【 授权许可】

Unknown