Effectiveness and Safety of Apatinib Plus Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer

Ji, Lin; Xu, Ying-Ying; Lin, Wei; Xue, Fangqin; Ye, Jianxin; Zang, Weidong; Cai, Lisheng; You, Jun; Xu, Jianhua; Cai, Jun; Tang, Yi-Hui; Xie, Jian‐Wei; Li, Ping; Zheng, Chao-Hui; Huang, Chang‐Ming

doi:10.1001/jamanetworkopen.2021.16240

Cited by 26 publications

(30 citation statements)

References 47 publications

(78 reference statements)

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“…There were no grade 4 adverse events or preoperative death observed. Compared with patients who did not experience adverse events, patients with grade 3 adverse events had a significantly lower average number of preoperative cycles, indicating that the incidence of adverse events was not related to the cumulative exposure to the drug ( 43 ). Results from clinical trials demonstrated that neoadjuvant chemotherapy combined with apatinib achieved a better survival benefit in the unresectable advanced gastric cancer with acceptable safety.…”

Section: Clinical Efficacy In Advanced Gastric Cancermentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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Digestive system malignancies are one of the primary causes of cancer-related death. Meanwhile, angiogenesis has been proved to play an important role in the process of cancer neovascularization. Apatinib, a novel targeted antiangiogenic molecule, could generate highly selective competition in the vascular endothelial growth factor receptor-2, involved in tumor progression and metastasis. It has been implied as a promising cancer treatment agent that can prevent tumor cell proliferation meanwhile inhibit tumor angiogenesis. Furthermore, completed clinical trials demonstrated that apatinib could prolong the progression-free survival and overall survival in advanced gastric cancer and primary liver cancer. Recent studies revealed that apatinib had a synergistic effect with immunotherapy as a second-line and third-line treatment regimen for some other cancers. In this review, we summarize the pharmacological properties of apatinib and the latest clinical application in chemotherapy-refractory patients with advanced digestive system cancer. Based on the comparable survival results, the molecular mechanisms of apatinib are prospective to include the antiangiogenic, apoptosis-inducing, and autophagy-inducing properties in the corresponding signaling pathway. Treatment of apatinib monotherapy or combination immunotherapy remains the optimal option for patients with digestive system malignancies in the future.

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Section: Clinical Efficacy In Advanced Gastric Cancermentioning

confidence: 99%

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Huang

Zhang

et al. 2022

Front. Immunol.

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“…To our knowledge, this is the first study to evaluate the concomitant use of a VEGFR TKI and XELOX for patients with locally advanced adenocarcinoma of the stomach or GEJ in the neoadjuvant setting. Some similar studies also investigated neoadjuvant apatinib combined with chemotherapy (S-1 and oxaliplatin) but only reported short-term efficacy (R0 resection rate [ 30 ] or pRR [ 31 ]). Our study was first to report the survival outcomes in this setting.…”

Section: Discussionmentioning

confidence: 99%

“…In the study by Zheng et al which enrolled 29 patients with LAGC, the ORR was 79.3% and pRR was 37.9% [ 31 ]. In another study by Lin et al which enrolled 48 patients with LAGC, the ORR was 75% and pRR was 25% [ 30 ]. In the present study, the ORR was 78.1% and pRR was 34.4%.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant apatinib combined with oxaliplatin and capecitabine in patients with locally advanced adenocarcinoma of stomach or gastroesophageal junction: a single-arm, open-label, phase 2 trial

Tang

Wang

et al. 2022

BMC Med

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Background Adding anti-angiogenics to neoadjuvant chemotherapy for localized gastric cancer is recognized as a promising strategy, but its clinical value remains to be defined. Methods This single-center, single-arm, phase 2 trial included patients with locally advanced (cT3/4aN+M0) adenocarcinoma of the stomach or gastroesophageal junction (GEJ) who received three cycles of intravenous oxaliplatin (135 mg/m2 on day 1), oral capecitabine (1000 mg/m2 twice daily on days 1 to 14), and oral apatinib for 21 days (250 mg once daily in the first two cycles, and further increased to 500 mg daily in the third cycle based on whether any adverse event of grade 3 or worse occurred), and an additional cycle of oxaliplatin plus capecitabine, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was the proportion of patients who achieved an objective response according to RECIST version 1.1. Results Between April 28, 2017, and October 23, 2019, 37 patients were screened and 35 participants were included. Of the 32 patients assessable for efficacy and safety, objective responses were achieved in 25 (78.1%; 95% confidence interval [CI], 60.0% to 90.7%) patients. Thirty-one (96.9%) patients received R0 resection, two (6.3%) patients achieved pathological complete response, and 11 (34.4%) patients achieved pathological response. At the data cutoff date (September 30, 2021), the median event-free survival was 42.6 (95% CI, 16.2 to not reached) months, and the median overall survival was not reached. The most common grade 3 or 4 treatment-emergent adverse events were hypertension (9/32, 28.1%), thrombocytopenia (7/32, 21.9%), and neutropenia (5/32, 15.6%). Seven (21.9%) patients developed surgical complications, and the most common one was intra-abdominal abscess (4/32, 12.5%). Conclusions The concomitant use of apatinib, oxaliplatin, and capecitabine as neoadjuvant therapy showed promising efficacy and manageable safety profile in patients with locally advanced adenocarcinoma of the stomach or GEJ, and further phase 3 study is warranted. Trial registration This study was registered with ClinicalTrial.gov (NCT03229096).

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“…Apatinib is a new tyrosine kinase inhibitor that exhibits significant antitumor activity in several solid tumors including HCC and gastric cancer by targeting VEGF receptor-2 (VEGFR-2) to inhibit tumor angiogenesis. 50 , 51 Fibrosis promotes angiogenesis by upregulating the expression of VEGF and its receptor VEGFR-2; 30 high ROS also increases the secretion of VEGF. 52 Autocrine VEGF-induced VEGFR2 overexpression can enhance the treatment efficiency of apatinib in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells

Zhang¹,

Xie²,

Lai³

et al. 2022

JHC

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Purpose Functional analysis was performed to elucidate the mechanism by which hepatocellular carcinoma (HCC) outcome-associated mutation in the hepatitis B virus X ( HBx ) gene modifies the HCC process. Methods Proliferation, invasion, migration, and apoptosis assays were performed, and changes in fibrosis, intracellular reactive oxygen species (ROS), and cytokine levels were measured. The differences between variables were evaluated by Student’s t -test. Results The influence of two previously identified nonsynonymous mutation, C1653T and T1753C, on HCC cells was assessed. With regard to HBX-induced promotion of proliferation (p < 0.01), invasion (p < 0.01) and migration (p < 0.01), the C1653T mutation displayed a significant additive effect in these assays (P < 0.05). The subsequent apoptosis assay indicated that HBX could inhibit apoptosis (P < 0.01), whereas the C1653T mutation markedly amplified this effect in HCC cells (P < 0.01). Furthermore, the tumor growth-promoting effect of HBX was confirmed in a mouse xenograft model of HCC (P < 0.05), and the C1653T mutation was observed to amplify this effect (P < 0.05). To further investigate the mechanism by which the C1653T mutation enhances malignancy in HCC cells, fibrosis, intracellular ROS, and cytokine levels were measured. The C1653T mutant increased fibrosis and intracellular ROS level, and altered monocyte chemotactic protein-1 and interleukin-18 expression in HepG2 cells. Drug sensitivity test revealed that the C1653T mutation is sensitive to apatinib treatment and that overexpression of vascular endothelial growth factor might be involved in this process. Conclusion Our data indicate that the C1653T mutation of HBx promotes HCC malignancy by altering the levels of fibrosis, ROS, and some cytokines. This mutation could serve as a potential biomarker for screening HCC patients to determine apatinib treatment efficacy.

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Effectiveness and Safety of Apatinib Plus Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer

Cited by 26 publications

References 47 publications

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Neoadjuvant apatinib combined with oxaliplatin and capecitabine in patients with locally advanced adenocarcinoma of stomach or gastroesophageal junction: a single-arm, open-label, phase 2 trial

Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells

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