Efficacy and Safety of Apatinib in Stage IV Sarcomas: Experience of a Major Sarcoma Center in China

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Oct 4

PMID 28969086

Citations 42

Authors

Feng Li

Zhichao Liao

Jun Zhao

Gang Zhao

Xubin Li

Xiaoling Du

Yun Yang

Jilong Yang

Affiliations

Soon will be listed here.

Abstract

Purpose: This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy.

Materials And Methods: The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.0 criteria. Progression free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse effects (AEs) were reviewed and evaluated.

Results: Patients was administered Apatinib for 0 to 9 cycles with the median of 3.2 cycles. Median follow-up time was 8.4 months (1 to 12 months). Ten of 16 patients received at least 1 complete cycle of Apatinib treatment were eligible for the efficacy analysis. The median PFS was 8.84 months. Two patients achieved partial response (PR) and 6 patients achieved stable disease (SD). Two patients were evaluated as progression disease (PD) and one patient died of disease progression. The ORR was 20.0% (2/10) and the DCR was 80.0% (8/10). The most common grade 3/4 treatment-related AEs were hypertension (18.7%), hand-foot syndrome (12.5%) and proteinuria (6.3%). No drug-related severe AEs occurred.

Conclusion: CApatinib treatment in this exploratory study exhibited objective efficacy and manageable toxicity in stage IV sarcoma patients who failed in chemotherapy. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

Citing Articles

Ovarian Angiosarcoma With Intractable Intraperitoneal Hemorrhage: A Case Report and Review of the Literature.

Tsuchiya N, Imai Y, Cho T, Ogawara Y, Mizushima T, Takase H Cureus. 2025; 17(1):e76849.

PMID: 39901995 PMC: 11788454. DOI: 10.7759/cureus.76849.

Malignant gastrointestinal neuroectodermal tumor: a case report and literature review.

Su D, Yang H, Zhao M, Zhou H, Wu J, Zhao Z Ann Med Surg (Lond). 2023; 85(12):6196-6201.

PMID: 38098564 PMC: 10718339. DOI: 10.1097/MS9.0000000000001400.

Apatinib Functioned as Tumor Suppressor of Synovial Sarcoma through Regulating miR-34a-5p/HOXA13 Axis.

Feng Q, Wang D, Guo P, Zhang Z, Feng J Comput Math Methods Med. 2022; 2022:7214904.

PMID: 36276991 PMC: 9581677. DOI: 10.1155/2022/7214904.

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

Wang X, Wang J, Sun B, Sun Y, Liu N, Niu X Ann Transl Med. 2022; 10(18):961.

PMID: 36267758 PMC: 9577742. DOI: 10.21037/atm-22-3250.

Effective Treatment of Low-Grade Myofibroblastic Sarcoma with Apatinib: A Case Report and Literature Review.

Lin Y, Gao X, Liu Z, Liu Z, Li Y, Liang R Pharmgenomics Pers Med. 2022; 15:573-582.

PMID: 35698620 PMC: 9188403. DOI: 10.2147/PGPM.S359492.

References

Tian S, Quan H, Xie C, Guo H, Lu F, Xu Y . YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011; 102(7):1374-80. PMC: 11158267. DOI: 10.1111/j.1349-7006.2011.01939.x. View

Hu X, Zhang J, Xu B, Jiang Z, Ragaz J, Tong Z . Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer. Int J Cancer. 2014; 135(8):1961-9. DOI: 10.1002/ijc.28829. View

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

Heudel P, Cassier P, Derbel O, Dufresne A, Meeus P, Thiesse P . Pazopanib for the treatment of soft-tissue sarcoma. Clin Pharmacol. 2012; 4:65-70. PMC: 3508654. DOI: 10.2147/CPAA.S33195. View

Roviello G, Ravelli A, Polom K, Petrioli R, Marano L, Marrelli D . Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. Cancer Lett. 2016; 372(2):187-91. DOI: 10.1016/j.canlet.2016.01.014. View

Zucali P, Bertuzzi A, Soto Parra H, Campagnoli E, Quagliuolo V, Santoro A . The "old drug" dacarbazine as a second/third line chemotherapy in advanced soft tissue sarcomas. Invest New Drugs. 2007; 26(2):175-81. DOI: 10.1007/s10637-007-9086-z. View

Tong X, Wang F, Liang S, Zhang X, He J, Chen X . Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells. Biochem Pharmacol. 2012; 83(5):586-97. DOI: 10.1016/j.bcp.2011.12.007. View

Eftekhari F . Imaging assessment of osteosarcoma in childhood and adolescence: diagnosis, staging, and evaluating response to chemotherapy. Cancer Treat Res. 2010; 152:33-62. DOI: 10.1007/978-1-4419-0284-9_3. View

Tang J, Markham N, Lin Y, McMurtry I, Maxey A, Kinsella J . Inhaled nitric oxide attenuates pulmonary hypertension and improves lung growth in infant rats after neonatal treatment with a VEGF receptor inhibitor. Am J Physiol Lung Cell Mol Physiol. 2004; 287(2):L344-51. DOI: 10.1152/ajplung.00291.2003. View

10.

Haduong J, Martin A, Skapek S, Mascarenhas L . Sarcomas. Pediatr Clin North Am. 2014; 62(1):179-200. DOI: 10.1016/j.pcl.2014.09.012. View

11.

Longhi A, Ferrari S, Bacci G, Specchia S . Long-term follow-up of patients with doxorubicin-induced cardiac toxicity after chemotherapy for osteosarcoma. Anticancer Drugs. 2007; 18(6):737-44. DOI: 10.1097/CAD.0b013e32803d36fe. View

12.

Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y . Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016; 34(13):1448-54. DOI: 10.1200/JCO.2015.63.5995. View

13.

Kumar S, Marfatia R, Tannenbaum S, Yang C, Avelar E . Doxorubicin-induced cardiomyopathy 17 years after chemotherapy. Tex Heart Inst J. 2012; 39(3):424-7. PMC: 3368447. View

14.

Mi Y, Liang Y, Huang H, Zhao H, Wu C, Wang F . Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010; 70(20):7981-91. PMC: 2969180. DOI: 10.1158/0008-5472.CAN-10-0111. View

15.

Lamplot J, Denduluri S, Qin J, Li R, Liu X, Zhang H . The Current and Future Therapies for Human Osteosarcoma. Curr Cancer Ther Rev. 2016; 9(1):55-77. PMC: 4730918. DOI: 10.2174/1573394711309010006. View

16.

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

17.

Folkman J . Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action. Exp Cell Res. 2005; 312(5):594-607. DOI: 10.1016/j.yexcr.2005.11.015. View

18.

von Mehren M, Randall R, Benjamin R, Boles S, Bui M, Casper E . Soft tissue sarcoma, version 2.2014. J Natl Compr Canc Netw. 2014; 12(4):473-83. DOI: 10.6004/jnccn.2014.0053. View

19.

Blay J, Van Glabbeke M, Verweij J, Van Oosterom A, Le Cesne A, Oosterhuis J . Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy. Eur J Cancer. 2002; 39(1):64-9. DOI: 10.1016/s0959-8049(02)00480-x. View

20.

Federman N, Bernthal N, Eilber F, Tap W . The multidisciplinary management of osteosarcoma. Curr Treat Options Oncol. 2009; 10(1-2):82-93. DOI: 10.1007/s11864-009-0087-3. View