Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib.

Bin Zhao,Hong Zhao

doi:10.18632/oncotarget.21217

Abstract

Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of several malignancies. As a non-traditional cytotoxic chemotherapeutic agent, regorafenib is often associated with hematologic toxicities. Here we searched PubMed and Embase up to June 2017 for relevant clinical trials. Eligible studies include trials in which subjects treated with 160 mg of regorafenib daily during the first 21 days of each 28-day cycle, and adequate safety data profile reporting thrombocytopenia, anemia, neutropenia and leucopenia. Statistical analyses were conducted to calculate the overall incidences, relative risks (RRs) and their 95% confidence intervals (CIs). A total of 2,341 subjects from 16 trials were included in the present studies. The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib-treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI, 3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all-grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06) anemia. Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician.

Highlights

Tyrosine kinase inhibitors (TKIs) are small molecules that bind to the activation domain of tyrosine kinase receptors, and have emerged as an important kind of anti-cancer agents
Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician
Regorafenib can inhibit the activity of angiogenic, stromal and oncogenic tyrosine kinases by targeting vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2 and VEGFR3), tyrosine protein kinase receptor Ret, tyrosine-protein kinase TIE-2, basic fibroblast growth factor receptor-1, platelet-derived growth factor beta, proto-oncogene RAF-1, c-KIT, BRAF and p38 MAP kinase [1, 2]. It has been approved by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (CRC) [3], advanced gastrointestinal stromal tumor (GIST) [4] and recently, advanced hepatocellular carcinoma (HCC) [5]

Summary

INTRODUCTION

Tyrosine kinase inhibitors (TKIs) are small molecules that bind to the activation domain of tyrosine kinase receptors, and have emerged as an important kind of anti-cancer agents. Regorafenib ( referred as Stivarga, BAY 73-4506) can inhibit the activity of angiogenic, stromal and oncogenic tyrosine kinases by targeting vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2 and VEGFR3), tyrosine protein kinase receptor Ret, tyrosine-protein kinase TIE-2, basic fibroblast growth factor receptor-1, platelet-derived growth factor beta, proto-oncogene RAF-1, c-KIT, BRAF and p38 MAP kinase [1, 2] It has been approved by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (CRC) [3], advanced gastrointestinal stromal tumor (GIST) [4] and recently, advanced hepatocellular carcinoma (HCC) [5]. Here we conducted a systematic review and meta-analysis of available clinical studies to determine the overall incidence and risk of developing hematologic toxicities in subjects treated with regorafenib

RESULTS

DISCUSSION

MATERIALS AND METHODS

Literature search and study selection