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

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