<p>Apatinib enhances chemosensitivity of gastric cancer to paclitaxel and 5-fluorouracil</p>

Abstract

Background and aim: Paclitaxel (PTX) plus 5-fluorouracil (5-Fu) has become the standard chemotherapy for advanced gastric cancer (GC). Apatinib, a small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, improves outcomes in GC patients as a third-line treatment. However, its impact on the chemosensitivity of GC remains to be determined. Hence, we aimed to assess the efficacy and safety of apatinib combined with chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was determined by Cell Counting Kit-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combination index values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 patients with late-stage GC were enrolled to explore the efficacy and safety of PTX/Tegafur Gimeracil Oteracil Potassium (S1) (PS) chemotherapy plus apatinib in conversion surgery. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo. The zebrafish embryo xenograft model also demonstrated that apatinib significantly enhanced the antitumor activity of PTX and 5-Fu. Apatinib plus PS chemotherapy was well tolerated before surgery. Objective response to preoperative SPA treatment was achieved in all 4 patients. No postoperative bleeding events or wound-healing complications were observed. No postperative morbidity occurred and no morbidity was encountered. Pathological examination showed that all patients had grade Ib pathological response. Conclusion: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that a combination of PS chemotherapy with apatinib may be an efficient and acceptable safety treatment for late-stage GC, especially in conversion surgery.

Efficacy of Conversion Surgery Following Apatinib Plus Paclitaxel/S1 for Advanced Gastric Cancer With Unresectable Factors: A Multicenter, Single-Arm, Phase II Trial

“…Previous studies about bevacizumab demonstrated that anti-angiogenic agents should be better discontinued at least 5–8 weeks prior to surgery and not be restarted until 28 days after the surgery in the setting of neoadjuvant and conversion therapy of metastatic colorectal cancer ( Gruenberger et al, 2008 ; Xu et al, 2019a ). Our data confirmed that, the duration of withdrawal apatinib for 4 weeks, the interval between radical gastrectomy and the last dose of apatinib, did not increase the rate of complications in metastatic GC patients.…”

“…As mentioned in the previous article ( Xu et al, 2019a ), apatinib was administered at a dose of 500 mg once a day continuously. PTX at a dose of 130 mg/m 2 was given on day 1 as a 2 h intravenous infusion with standard premedication.…”

Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer

“…Zygote period cleaving eggs were transferred to six-well plastic cell culture plates filled with embryo medium E3. The eggs (10-12 per well) were exposed to RSC (50 mM), 5-FU (50 mM), and MM-129 (10 mM) for 3 h 24,25 . The final volume of the medium in each well was 2 mL.…”

Oral maintenance therapy using apatinib combined with S-1/capecitabine for esophageal squamous cell carcinoma with residual disease after definitive chemoradiotherapy

“…These findings were confirmed in a phase II study, which showed that the monotherapy achieved an OR of 7.7%, with median PFS and OS at 4.63 and 6.57 months, respectively [ 31 ]. Moreover, in vivo and in vitro studies have demonstrated that apatinib significantly increased the sensitivity to paclitaxel, cisplatin, and 5-Fu, suggesting that it is feasible to combine apatinib with other chemotherapeutic agents to yield a synergistic effect [ 32 – 34 ].…”