Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies

Procaccio, Letizia; Damuzzo, Vera; Sarra, Francesca Di; Russi, Alberto; Todino, Federica; Dadduzio, Vincenzo; Bergamo, Francesca; Prete, Alessandra Anna; Lonardi, Sara; Prenen, Hans; Palozzo, Angelo Claudio; Loupakis, Fotios

doi:10.1007/s40264-018-0776-6

Cited by 23 publications

(13 citation statements)

References 153 publications

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“…The progression-free survival period and the overall survival period reached 3.2 and 5.3 months, respectively, consistent with the results of many previous studies. Another study showed that apatinib was safe and feasible for advanced esophageal squamous cell carcinoma with better survival bene t and lighter toxic response than traditional second-line chemotherapy, and was considered to be suitable for second-line or subsequent treatment of esophageal squamous cell carcinoma [28]. In this experiment, the patient's partial response rate was 26.09%, the disease control rate was 67.39%, the median progression-free survival was 3.7 months and the median overall survival was 7.2 months.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma

Liu

Wang

et al. 2020

Expert Review of Clinical Pharmacology

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Background: To investigate the clinical e cacy,safety and prognostic factors of the therapy that apatinib is used for maintenance treatment in patients with advanced esophageal squamous cell carcinoma.Methods: We select 46 patients with advanced esophageal squamous cell carcinoma treated with radiotherapy and chemotherapy in our hospital from January 2017 to February 2019, all of them were treatment with apatinib. Analysis the clinical e cacy, adverse reactions and prognostic factors. Meanwhile, the expression of patients'VEGFR-2 NF-kB was detected by immunohistochemical SABC method,and the microvessel density and microlymphatic tube density were counted.Analysis of the relationship between indicators and MVD, MLVD counts and the e cacy of apatinib.Results: We found that oral treatment of apatinib in VEGFR-2 NF-kB positive group was better than that in negative group. The partial remission rate of patients was 26.09%; the disease control rate was 67.39%.The main adverse reactions were hypertension (60.87%); hand and foot syndrome (34.77%); proteinuria (36.96%). The degree of adverse reactions was mainly grade 1~2. The median progression-free survival was 3.7 months and the median overall survival was 7.2 months.Log-Rank univariate analysis showed that the degree of adverse reactions and ECOG score were related to OS in patients with advanced esophageal squamous cell carcinoma.Cox multivariate regression analysis showed that the degree of adverse reactions and ECOG score were independent factors affecting OS in patients with advanced esophageal squamous cell carcinoma. Conclusion:Positive expression of VEGFR-2 and NF-kB can be used as a biological reference target for targeted treatment of oral apatinib. Apatinib has a certain clinical effect in the maintenance treatment of advanced esophageal squamous cell carcinoma patients after treatment, with mild adverse reactions and high safety.

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Section: Discussionmentioning

confidence: 99%

Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma

Liu

Wang

et al. 2020

Expert Review of Clinical Pharmacology

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“…AP has been shown to inhibit VEGF-mediated intracellular neovascularization signals in vivo, thereby promoting tumor cell apoptosis and inhibiting cell proliferation. AP alone or in combination with chemotherapy drugs inhibits the growth of several human tumors by inhibiting angiogenesis (Chen et al 2018;Liu et al 2017;Procaccio et al 2019). AP has also been reported to improve radiosensitivity of several human tumors (Hu et al 2018;Hu et al 2019;Liang et al 2020;Liao et al 2019;Zhao et al 2017a).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "A novel role for apatinib in enhancing radiosensitivity in non-small cell lung cancer cells by suppressing the AKT and ERK pathways (v0.1)"

Castañeda-Saucedo¹

2021

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“…Angiogenesis is an essential mechanism for the metastasis and proliferation of cancer cells (4). Thus, anti-angiogenetic drugs, including bevacizumab and aflibercept, are regarded as important for colorectal cancer therapy (5). It has been hypothesized that angiogenesis in cancer is caused by cancer cells (5).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, anti-angiogenetic drugs, including bevacizumab and aflibercept, are regarded as important for colorectal cancer therapy (5). It has been hypothesized that angiogenesis in cancer is caused by cancer cells (5). However, recent studies revealed that stromal cells in cancer cause angiogenesis (6,7).…”

Section: Introductionmentioning

confidence: 99%

Eicosapentaenoic acid suppresses angiogenesis via reducing secretion of IL‑6 and VEGF from colon cancer‑associated fibroblasts

et al. 2019

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Eicosapentaenoic acid (EPA) improves interleukin (IL)-6 hypercytokinemia in patients with advanced cancer due to its anti-inflammatory effects. This EPA mechanism has been revealed to lead to several anticancer effects. While the effects of EPA on cancer cells have been investigated, particularly in terms of angiogenesis, its effects on the tumor stroma remain unclear. In the present study, the authors clarified the role of EPA in cancer angiogenesis against colon cancer-associated fibroblasts (CAFs) from the colon stroma. With established human CAFs and normal fibroblasts from colon stroma (NFs), the authors evaluated IL-6 and vascular endothelial growth factor (VEGF) secretion with or without EPA treatment using ELISA. The signal inhibition of mitogen-activated protein kinase (ERK) in CAFs by EPA was evaluated using western blotting. In vitro anti-angiogenesis effects were evaluated by the angiogenesis assay on Matrigel using human umbilical vein endothelial cells (HUVECs) cultured with the supernatant obtained from CAF cultures with or without EPA. IL-6 secretion was greater from CAFs compared with that from NFs and stimulation with lipopolysaccharide (LPS) resulted in greater IL-6 secretion from the two fibroblast types compared with that from fibroblasts without LPS stimulation. While LPS stimulation increased VEGF secretion from the two fibroblast types, EPA decreased IL-6 and VEGF secretion from CAFs. Western blotting revealed that the addition of 30 µM EPA inhibited the ERK phosphorylation signal in CAFs. Furthermore, the angiogenesis assay with Matrigel revealed that the CAF culture supernatants treated with EPA suppressed tubular formation in HUVECs. These reductions may have been caused by the inhibition of ERK phosphorylation by EPA. Thus, EPA reduces cancer angiogenesis associated with CAFs. Additional studies will be needed to clarify the continuous anti-angiogenetic effect of chemotherapy using angiogenesis inhibitors (e.g. bevacizumab and aflibercept) in conjunction with or without EPA, and the clinical usage of EPA in conjunction with chemotherapy in vivo.

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Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies

Cited by 23 publications

References 153 publications

Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma

Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma

Peer Review #1 of "A novel role for apatinib in enhancing radiosensitivity in non-small cell lung cancer cells by suppressing the AKT and ERK pathways (v0.1)"

Eicosapentaenoic acid suppresses angiogenesis via reducing secretion of IL‑6 and VEGF from colon cancer‑associated fibroblasts

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