Tumor feeding artery contraction and metastasis inhibition after transarterial chemoembolization combined with apatinib for hepatocellular carcinoma: A propensity score matching study
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To investigate the change of tumor feeding artery diameter and the efficacy of metastasis inhibition after transarterial chemoembolization (TACE) combined with apatinib or TACE monotherapy for patients with advanced hepatocellular carcinoma who without metastasis.A total of 616 consecutive patients who received the treatment of TACE-apatinib or TACE in our center was enrolled. Propensity score matching (PSM) analysis was used to reduce bias. The overall survival (OS), OS-after-metastasis (OSM), time to progression (TTP), time to metastasis (TTM), time to vessel or organ metastasis (TVOM), time to lymph node metastasis, and tumor feeding artery diameter between the two treatment groups were compared.A total of 113 pairs of patients were eligible after the PSM. Time to lymph node metastasis between the two groups was not significantly different (P > 0.05). The tumor feeding artery diameter was significantly smaller after TACE-apatinib management (P < 0.001). Median OS (P < 0.001) and OSM (P < 0.001) were significantly longer in the TACE-apatinib group compared with the TACE group. Median TTP (P < 0.001), TTM (P < 0.001), and TVOM (P < 0.001) were significantly prolonged in TACE-apatinib group.TACE-apatinib treatment could improve the prognosis compared with TACE alone, and inhibit metastasis after TACE procedure with contracted tumor feeding artery for advanced HCCs without metastasis.Keywords:
Apatinib
Transcatheter arterial chemoembolization
Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer. The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects. We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle. Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable. Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study.
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Objective To study blood supply from the omental artery to hepatic carcinoma and evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)via omental artery.Methods 19 cases of hepatic tumor fed by the omental artery underwent TACE of the omental artery.The omental branch angiographic features,tumor location,clinical observation,laboratory tests,imageology were evaluated,and finally were correlated with the angiographic findings of the omental branch.Results The tumor was located at the surface of the right lobe of the liver in 16 patients and at the lower edge of segment 4 in three patient.29 omental branches that fed HCC were observed angiographically.15omental branches(78.9%)could be successfully embolized.Hepatic hemostasis was achieved in all patients with ruptured HCC.Tumor recurred in 71%of patients who underwent successful TACE of the omental branch.Severe complications were not observed in any patient.Conclusion The omental artery collateral supply to HCC occur in HCCs located on the surface of the right lobe of the liver and in patients who have undergone multiple TACE procedures in the past.TACE of the omental artery is safe and has become technically feasible in almost all patients,although the tumor recurrence rate is extremely high.
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Abstract This study aimed to investigate the anti‐tumour effect of apatinib on extensive‐stage small cell lung cancer (SCLC) and elucidate the associated mechanisms. NCI‐H345 cells were selected as model cells because of high expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and phosphorylated‐VEGFR2 (pVEGFR2). Cells were exposed to recombinant human VEGF (rhVEGF) and apatinib. Cells were then divided into eight groups, namely, control, rhVEGF, apatinib, rhVEGF+apatinib, serum‐free medium (SM), SM+rhVEGF, SM+apatinib and SM+rhVEGF+apatinib. In comparison with the control group, cell proliferation in vitro in apatinib, SM, SM+apatinib and SM+rhVEGF+apatinib groups was inhibited, particularly in SM+apatinib group. The effect of apatinib on tumour growth in vivo was investigated using a mouse xenograft tumour model. In comparison with the control group, tumour sizes were reduced in apatinib‐treated group on days 34 and 37. Immunohistochemical and immunofluorescence staining revealed that VEGF, pVEGFR2, PI3K, AKT, p‐ERK1/2, Ki‐67 and CD31 in the tumour cells of apatinib‐treated group were downregulated compared with control group. Haematoxylin and eosin staining revealed that apatinib promoted the necrosis of SCLC cells in vivo. In conclusion, apatinib inhibited the growth of SCLC cells by downregulating the expression of VEGF, pVEGFR2, p‐PI3K, p‐AKT, p‐ERK1/2, Ki‐67 and CD31.
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Programmed cell death protein 1 (PD-1) inhibitor plus apatinib is reported to be a promising strategy for advanced cancers. Moreover, a PD-1 inhibitor or apatinib exerts a certain efficacy in advanced colorectal cancer (CRC), whereas their synergistic effect is unclear. This study aimed to evaluate the treatment efficacy and safety of a PD-1 inhibitor plus apatinib in advanced CRC patients.In total, 45 advanced CRC patients who received a PD-1 inhibitor plus apatinib (PD-1 inhibitor plus apatinib group, N=20) or apatinib monotherapy (apatinib group, N=25) as third-line therapies were enrolled in the current study.The objective response rate (20.0% vs. 8.0%) (P=0.383) and disease control rate (70.0% vs. 52.0%) (P=0.221) were numerically increased in the PD-1 inhibitor plus apatinib group, respectively, compared with the apatinib group, but no statistical significance was observed. The median progression-free survival (PFS) was 7.5 versus 4.8 months; the 1-year PFS rate was 32.5% versus 9.9%; the median overall survival (OS) was 12.3 versus 8.7 months; and the 1-year OS rate was 50.7% versus 27.0% in the PD-1 inhibitor plus apatinib group versus the apatinib group, respectively. PFS (P=0.038) and OS (P=0.048) were prolonged in the PD-1 inhibitor plus apatinib group compared with the apatinib group. PD-1 inhibitor plus apatinib (versus apatinib) was independently associated with longer PFS (P=0.012) and OS (P=0.009). The majority of the adverse events were of grade 1-2, wherein the incidence was similar between groups, except for the fact that the incidence of capillary proliferation was elevated in the PD-1 inhibitor plus apatinib group compared with the apatinib group (25.5% versus 0.0%) (P=0.013).PD-1 inhibitor plus apatinib presents a potential improvement in efficacy and survival benefit compared with apatinib monotherapy, with tolerable safety in advanced CRC patients.
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Apatinib (YN968D1) is a novel and highly selective tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2) and is approved as a third-line and subsequent-line treatment for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China.Apatinib is also widely studied in other solid tumors.With the increase in clinical research of apatinib, its adverse effects have also received widespread attention.Hence, this article summarizes the pharmacological properties of apatinib and reviews its clinical use in advanced or metastatic cancers.We highlight the common adverse reactions of apatinib in clinical applications and we also clarify the corresponding prevention and intervention measures.Overall, this review will help us better understand the safety and efficacy of apatinib treatment.
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Introduction: Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients.Areas covered: The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo.Expert opinion: Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.
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Background and purpose: Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that targets VEGFR-2. Recent clinical trials have revealed its broad-spectrum anticancer effect. However, most recent studies of apatinib have involved single-arm studies with insufficient cases, different doses of drugs, and different incidences of adverse events (AEs), which has resulted in a lack of accurate measurement of the efficacy and safety of apatinib. Thus, we performed this meta-analysis to evaluate the efficacy and safety of apatinib. Methods: In total, 21 studies from five databases (PubMed, ScienceDirect, ClinicalTrials.gov , China National Knowledge Infrastructure [CNKI], and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed using Stata 14.0 software. We used objective response rate (ORR) and disease control rate (DCR) to evaluate the efficacy of apatinib for five major types of solid tumors. Additionally, we used the total incidence of AEs and the incidence of the three most common grade 3–4 AEs to evaluate the safety of apatinib. Results: The pooled results for the efficacy of apatinib in the treatment of different types of solid tumors revealed that patients treated with apatinib exhibited good disease control. In addition, it was likely that an increased dose of apatinib resulted in an increased ORR in lung and breast cancer and an increased DCR in liver and gastric cancer. Although AEs appeared in 84% of patients included in this meta-analysis, most of these AEs were of grades 1–2 and were well tolerated and controlled. The most common grade 3–4 AEs included hypertension, hand-foot syndrome, and proteinuria. Importantly, there were no significant differences in these grade 3–4 AEs with higher doses of apatinib. Conclusion: Apatinib is a novel VEGFR-2 inhibitor with proven efficacy and safety for solid tumors. The meta-analysis reveals the broad-spectrum anticancer effect of apatinib. Keywords: apatinib, solid tumors, objective response rate, disease control rate, adverse events
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This study aimed to compare the efficacy and safety of apatinib plus drug-eluting bead (DEB) transarterial chemoembolization (TACE), apatinib plus conventional TACE (cTACE) and apatinib alone in advanced intrahepatic cholangiocarcinoma (ICC) patients. We analyzed 35 advanced ICC patients retrospectively, including the apatinib plus DEB-TACE group (n=10), the apatinib plus cTACE group (n=12) and the apatinib group (n=13). Treatment response, survival data (including progression-free survival (PFS) and overall survival (OS)) and adverse events were assessed during the follow-up. Both the objective response rate (ORR) and the disease control rate (DCR) showed trends to be the highest in the apatinib plus DEB-TACE group (ORR: 84.6%/DCR: 100.0%), followed by the apatinib plus cTACE group (ORR: 75.0%/DCR: 91.7%) and then the apatinib group (ORR: 40.0%/DCR: 80.0%). PFS and OS were both the highest in the apatinib plus DEB-TACE group, followed by the apatinib plus cTACE group, and the shortest in the apatinib group, which was also confirmed by a multivariate Cox regression analysis. The incidences of adverse events were similar between the apatinib plus DEB-TACE group and the apatinib plus cTACE group but were higher in the apatinib plus DEB-TACE group and the apatinib plus cTACE than in the apatinib group; however, all of the adverse events were tolerable in the three groups. In conclusion, apatinib plus DEB-TACE is a promising therapeutic strategy for the treatment of advanced ICC.
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Background: Serum level of insulin-like growth factor-Ⅱ (IGF-Ⅱ) is associated with the prognosis of primary hepatocellular carcinoma. Thus, serum IGF-Ⅱ measurement is helpful for the evaluation of therapeutic efficacy in primary hepatocellular carcinoma. Aims: To investigate the effect of transcatheter arterial chemoembolization (TACE) on serum IGF-Ⅱ level in patients with primary hepatocellular carcinoma, and the clinical significance of serum IGF-Ⅱ measurement. Methods: 33 patients with primary hepatocellular carcinoma received TACE therapy and 48 healthy subjects served as controls in this study. The serum levels of IGF-Ⅱ were measured by radioimmunoassay in all patients and controls. Results: The serum level of IGF-Ⅱ in patients with primary hepatocellular carcinoma before and after TACE treatment were all significantly higher than that in normal controls (P0.001). After three times TACE treatment, the serum IGF-Ⅱ level decreased markedly than that before treatment (P0.05). During the treatment period, the serum IGF-Ⅱ level decreased gradually in patients who survived and increased in those who died. Conclusions: Serum level of IGF-Ⅱ that may reduce after TACE therapy in patients with primary hepatocellular carcinoma, is a marker for the prognosis and therapeutic efficacy evaluation of TACE in patients with primary hepatocellular carcinoma.
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