The safety of monoclonal antibodies for treatment of colorectal cancer

Berger, Martin D.; Lenz, Heinz‐Josef

doi:10.1517/14740338.2016.1167186

Cited by 25 publications

(14 citation statements)

References 70 publications

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“…As an off label use, Bevacizumab is applied intravitreally to treat age related macular degeneration with good clinical outcome and good safety [27,28]. The most common adverse events associated with systemically applied Bevacizumab in humans are hypertension, proteinuria, thromboembolism, bleeding, gastrointestinal perforation and prolonged wound healing [29]. Importantly, while potential systemic side effects were not explicitly addressed in our study, signs of intolerance or changed behavioral signs were not observed in any of the Bevacizumab treated animals within the period tested.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Tempfer

Kaser-Eichberger

Lehner

et al. 2018

Cell Physiol Biochem

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Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days postsurgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young's modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

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Section: Discussionmentioning

confidence: 99%

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Tempfer

Kaser-Eichberger

Lehner

et al. 2018

Cell Physiol Biochem

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“…Colorectal cancer is the fourth leading cause of cancer-related death worldwide. With the addition of biologicals to 5-fluorouracil (5-FU)-based treatment regimens, the outcome of metastatic colorectal cancer (mCRC) patients has markedly improved during the last decade (1). However, to further optimize treatment, new effective drugs are highly warranted.…”

Section: Introductionmentioning

confidence: 99%

A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab

Berger

Stintzing

Heinemann

et al. 2018

Clinical Cancer Research

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Vitamin D exerts its inhibitory influence on colon cancer growth by inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes involved in vitamin D transport, metabolism, and signaling are associated with outcome in metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI and bevacizumab. 522 mCRC patients enrolled in the FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with FOLFIRI/bevacizumab were included in this study. 278 patients receiving FOLFIRI and cetuximab (FIRE-3) served as a control cohort. Six SNPs in 6 genes () were analyzed. In the discovery cohort, AA carriers of the rs4588 SNP encoding for the vitamin D-binding protein, and treated with FOLFIRI/bevacizumab had a shorter overall survival (OS) than those harboring any C allele (15.9 vs. 25.1 months) in both univariable ( = 0.001) and multivariable analyses ( = 0.047). This association was confirmed in the validation cohort in multivariable analysis (OS 18.1 vs. 26.2 months, HR, 1.83; = 0.037). Interestingly, AA carriers in the control set exhibited a longer OS (48.0 vs. 25.2 months, HR, 0.50; = 0.021). This association was further confirmed in a second validation cohort comprising refractory mCRC patients treated with cetuximab ± irinotecan (PFS 8.7 vs. 3.7 months) in univariable ( = 0.033) and multivariable analyses ( = 0.046). rs4588 SNP might serve as a predictive marker in mCRC patients treated with FOLFIRI/bevacizumab or FOLFIRI/cetuximab. Whereas AA carriers derive a survival benefit with FOLFIRI/cetuximab, treatment with FOLFIRI/bevacizumab is associated with a worse outcome. .

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“…A previous study has found that anti-EGFR therapy can cause infusion-related reactions and skin alterations 39. Moreover, anti-VEGF therapy can cause arterial hypertension, venous and arterial thromboembolic events, and gastrointestinal perforations 40. Our meta-analysis indicated that, in the anti-EGFR group, there was a significant increase in Grade 3 toxicity or lower, including skin disorders, hypomagnesemia, and hypokalemia, whereas the patients in the anti-VEGF group experienced hypertension more often.…”

Section: Discussionmentioning

confidence: 98%

Efficacy and safety of anti-epidermal growth factor receptor therapy compared with anti-vascular endothelial growth factor therapy for metastatic colorectal cancer in first-line and second-line therapies: a meta-analysis

Wang

Gao

et al. 2016

OTT

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AimThis study aimed to compare anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy as first-line and second-line therapies in patients with KRAS exon 2 codon 12/13 wild-type (KRAS-WT) metastatic colorectal cancer (mCRC).MethodsMajor databases were systematically searched. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (95% CIs) were used to estimate the effect measures. Review Manager software version 5.3 was used for statistical analysis.ResultsSeven trials including ten articles were eligible in the meta-analysis. The patients treated with anti-EGFR as first-line therapy showed a longer overall survival (OS) for KRAS-WT and all RAS wild-type (RAS-WT) mCRC (HR =0.81, 95% CI: 0.72–0.92, P<0.01, n=5; HR =0.78, 95% CI: 0.66–0.93, P<0.01, n=3, respectively). The objective response rate (ORR) was better with the anti-EGFR therapy for KRAS-WT and all RAS-WT mCRC (OR =1.32, 95% CI: 1.11–1.56, P<0.01, n=5; OR =1.55, 95% CI: 1.21–2.00, P<0.01, n=3, respectively). There was no difference in progression-free survival (PFS) for KRAS-WT mCRC and all RAS-WT mCRC between the two groups (HR =1.00; 95% CI: 0.92–1.09, P=0.99, n=4; HR =0.92, 95% CI: 0.71–1.19, P=0.52, n=3, respectively). In addition, two trials provided data on the second-line therapy; there was no significant difference in OS and PFS for the second-line therapy, but a significant improvement in ORR was found in the anti-EGFR group (OR =1.91, 95% CI: 1.16–3.16, P=0.01, n=2). No difference in the conversion therapy (OR =1.34; 95% CI: 0.91–1.99; P=0.14, n=4) was observed between the two therapies.ConclusionOur results indicate that anti-EGFR therapy is superior to anti-vascular endothelial growth factor therapy for OS and ORR as a first-line therapy for KRAS-WT mCRC. In the second-line therapy, there was no significant difference in the survival outcomes on the basis of OS and PFS between the two groups. However, ORR improved significantly in the anti-EGFR group.

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The safety of monoclonal antibodies for treatment of colorectal cancer

Cited by 25 publications

References 70 publications

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab

Efficacy and safety of anti-epidermal growth factor receptor therapy compared with anti-vascular endothelial growth factor therapy for metastatic colorectal cancer in first-line and second-line therapies: a meta-analysis

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