Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials

Zhang, Hongliang; Huang, Zhenguang; Zou, Xiaoqin; Liu, Taotao

doi:10.18632/oncotarget.12666

Cited by 61 publications

(52 citation statements)

References 27 publications

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“…In the sample presented in this paper, it is noteworthy that immunization with CIGB-247 was safe and well tolerated in all these cases. In addition to this experimental evidence, a detectable VEGF-specific patients [54]. These clinical observations with CIGB-247 could be explained by the incomplete abrogation of platelet VEGF levels after immunization with CIGB-247 [55].…”

Section: Discussionmentioning

confidence: 92%

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

Ramírez

Díaz

Bequet-Romero

et al. 2020

Preprint

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Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 µg of antigen combined with 200 µg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. Conclusions: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.

show abstract

Section: Discussionmentioning

confidence: 92%

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

Ramírez

Díaz

Bequet-Romero

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The results of our study indicated that bevacizumab extended the time required for absorption of the hyphema from the anterior chamber. Bevacizumab use is known to cause wound healing complications (12); therefore, we believe that the extended duration required for hyphema resorption was due to disruption of the wound healing process. In a normal wound, the blood turns into a clot during the healing process.…”

Section: Discussionmentioning

confidence: 94%

The effect of intracameral bevacizumab on current hyphema

Polat¹,

Özkan²,

Akbaş³

et al. 2019

Ann Med Res

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The aim of this study was to investigate the effect of intracameral bevacizumab on the current hyphema. Material and Methods: The animals were assigned to the following 4 groups; Group 1: One 2.5 mg bevacizumab injection to the anterior chamber; Group 2: One 1.25 mg bevacizumab injection to the anterior chamber; Group 3: One 1cc balanced salt solution injection to the anterior chamber; and Group 4: Untreated hyphema group. Non-heparinized blood that obtained from the rabbit ear was used to fill the anterior chamber to create total hyphema. Intraocular pressures (IOP), hyphema resorption time, clot formation, peripheral synechia formation, and corneal staining were recorded. Results: IOP results were 26±1.2, 30±2.1, 24±2.9, and 22±0.0 mm Hg for groups 1, 2, 3, and 4, respectively, and were significantly higher in group 2 than in the other groups (p= 0.001). Resorption times of hyphema were 13±2.2, 13±3.2, 9±1.7, and 9±1.6 days for groups 1, 2, 3, and 4, respectively, and were significantly longer for the groups receiving bevacizumab than for the others (p=0.018). The clot formation scores were 0.16±0.41, 0.14±0.38, 0.86±0.38, and 1.0±0.0 for groups 1, 2, 3, and 4, respectively, and were significantly lower for the groups receiving bevacizumab than in the other groups (p= 0.002). The peripheral synechia formation scores were 0.0±0.0, 0.0±0.0, 0.43±0.53, and 0.50±0.54 for groups 1, 2, 3, and 4, respectively, and were not significantly different (p= 0.213). The corneal staining scores were 0.85±0.35, 0.86±0.38, 0.14±0.38, and 0.14±0.38 for groups 1, 2, 3, and 4, respectively, and were significantly higher for the groups receiving bevacizumab (p= 0.035). Conclusion: Intracameral bevacizumab may increase complications that related current hyphema.

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“…Finally, two individuals included in our present study were submitted to major urgent surgeries during immunization with CIGB-247 without reports of wound healing impairment. It is know that bevacizumab treatment increases the risk of bleeding and wound healing complications in cancer patients [54]. These clinical observations with CIGB-247 could be explained by the incomplete abrogation of platelet VEGF levels after immunization with CIGB-247 [55].…”

Section: Safety Profile and Immunogenicity Of Cigb-247 In Patients Wimentioning

confidence: 99%

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

Ramírez

Díaz

Bequet-Romero

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 µg of antigen combined with 200 µg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP.The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. Conclusions: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.

show abstract

Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials

Cited by 61 publications

References 27 publications

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

The effect of intracameral bevacizumab on current hyphema

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

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