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Bevacizumab
Kinds of Bevacizumab Terms modified by Bevacizumab Selected Abstracts"Spontaneous," delayed colon and rectal anastomotic complications associated with bevacizumab therapyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008David A. August MD Abstract Bevacizumab, a humanized monoclonal antibody used to treat recurrent and metastatic colorectal cancer, targets the vascular endothelial growth factor (VEGF) molecule. It is hypothesized that bevacizumab works by both depriving tumors of the neovascularity they require to grow, and by improving local delivery of chemotherapy through alterations of tumor vasculature permeability and Starling forces. Complications of bevacizumab treatment include bowel ischemia and perforation, but to date, these complications have only rarely been described as occurring at the site of presumably healed anastomoses following surgery. We report two cases of delayed, "spontaneous" low anterior colorectal anastomotic dehiscence and one right colon anastomotic colocutaneous fistula associated with bevacizumab therapy. After seeing three patients with complications arising from apparently healed low anterior colorectal or right colon anastomoses following initiation of bevacizumab therapy for treatment of metastatic colorectal cancer, we reviewed the experience of The Cancer Institute of New Jersey (CINJ) with use of bevacizumab in approximately 50 patients between April 2004 and December 2006. The three index cases had been treated surgically at CINJ but received chemotherapy elsewhere. None of the 50 patients receiving bevacizumab at CINJ who had previous colon or rectal anastomoses were identified as having this complication. The medical records of the three index cases were reviewed and analyzed. Additionally, a Medline search was performed to identify other reports documenting similar cases. Two reports of related cases were found in the literature. In two of our index cases who underwent low anterior anastomoses, the patients had received preoperative pelvic irradiation before their initial low anterior resection. In one of the two cases, the initial resection was complicated by an anastomotic leak requiring proximal diversion and then subsequent stoma takedown. In both cases, the dehiscence occurred more than 1 year after anastomosis, and became evident 1,10 months following initiation of bevacizumab treatment. In the third index case, a colocutaneous fistula arising from the anastomotic site presented 5 months following right colon resection and 3 months after starting adjuvant systemic therapy with FOLFOX (5-fluorouracil (5-FU), leucovorin, and oxaliplatin) and bevacizumab. Delayed colorectal anastomotic complications may occur in association with bevacizumab therapy. Contributing factors may include anastomotic leak at the time of the original operation and history of anastomotic irradiation. Clinicians treating patients who receive bevacizumab following colectomy for colorectal cancer should be aware of this possible life-threatening complication. These findings may also be relevant to the design of trials of the use of bevacizumab for the postoperative adjuvant treatment of patients with colorectal cancer. J. Surg. Oncol. 2008;97:180,185. © 2007 Wiley-Liss, Inc. [source] Spinal cord infarction in a patient with metastatic non-small cell lung cancer, receiving chemotherapy combined with bevacizumabASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Katherine MASSELOS Abstract Bevacizumab is an anti-angiogenesis agent that has many applications in the current management of patients with cancer, including advanced non-small cell lung cancer. Its value is however, not without side effects. We present the first reported case of spinal cord infarction in the setting of bevacizumab use in a 70-year old woman with advanced non-small cell lung cancer. [source] Role of novel targeted agents in the treatment of metastatic colorectal cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2007Dragan DAMIANOVICH Abstract Modern chemotherapy regimens, combining bolus or infused schedules of 5-fluorouracil (5-FU) with irinotecan or oxaliplatin, have significantly improved the treatment outcomes of patients with metastatic colorectal cancer (CRC). The addition of novel targeted agents to chemotherapy has the potential to increase the median survival of patients with metastatic CRC beyond 2 years. Bevacizumab, a monoclonal antibody (mAb) to vascular endothelial growth factor, has an established role in first-line treatment in combination with either 5-FU/leucovorin or irinotecan/5-FU/leucovorin regimens, while cetuximab, a mAb to epidermal growth factor receptor, in combination with irinotecan is more suitable for the treatment of refractory metastatic CRC. The use of bevacizumab in later stages of the disease and cetuximab in chemotherapy-naive patients as well as concurrent treatment with both agents is still under investigation. The landmark studies leading to the approval of these agents in the treatment of metastatic CRC as well as associated toxicity profiles and detailed treatment recommendations are discussed in this review. [source] Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Philippe Bonnin Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 ± 96 ,m to 271 ± 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source] Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damageACTA OPHTHALMOLOGICA, Issue 5 2010Sebastian Thaler Abstract. Purpose:, To evaluate the effects of intravitreally introduced vascular endothelial growth factor (VEGF) inhibitors in rat eyes with healthy retinal ganglion cells (RGC) and into others with N-methyl-D-aspartate (NMDA)-induced RGC damage. Methods:, Bevacizumab, ranibizumab and pegaptanib were intravitreally injected each at two different concentrations. Respective vehicles of the three substances served as controls. In a different group, additionally a rat anti-VEGF antibody was injected after NMDA treatment. Retrogradely labelled RGC were counted on retinal wholemounts 1 week or 2 months after intravitreal introduction of the VEGF inhibitors. Electron microscopy (EM) was performed on normal rat eyes 2 months after introduction of the VEGF inhibitors. Results:, RGC counts in healthy rat eyes were essentially unchanged from those of the control animals after the administration of both low and high concentrations of bevacizumab, ranibizumab or pegaptanib. Compared to the other two substances, however, high doses of pegaptanib and its respective vehicle significantly decreased RGC after 1 week and led to a marked increase of mitochondrial swelling in EM. In eyes with NMDA-induced RGC damage, no changes of RGC numbers were detected after rat anti-VEGF antibody or bevacizumab, ranibizumab and pegaptanib at both tested concentrations. Conclusions:, Even at higher doses, bevacizumab and ranibizumab showed no toxic effects on RGC in vivo in either untreated rats or in the NMDA-induced RGC damage model. Also a rat anti-VEGF antibody showed no adverse effects after NMDA. Anti-VEGF therapy therefore appears safe even for eyes with additional excitotoxic RGC damage. Potential harm from the pegaptanib carrier solution at very high local concentrations cannot be excluded. [source] Clinical and histological findings after intravitreal injection of bevacizumab (Avastin®) in a porcine model of choroidal neovascularizationACTA OPHTHALMOLOGICA, Issue 3 2010Nathan Lassota Abstract. Purpose:, To examine the effect of intravitreally injected bevacizumab (Avastin®) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. Methods:, Choroidal neovascularization was induced surgically in 11 porcine eyes by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. Results:, Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes leaking on FA, whereas only one of five bevacizumab-injected eyes exhibited leakage. On histological examination, all 11 eyes contained CNV membranes of similar size, regardless of treatment. The number of vascular endothelial cells was significantly reduced (p = 0.03) in CNV membranes from eyes that had been injected with bevacizumab when compared with CNV membranes from placebo-injected eyes. There was a trend towards more retinal pigment epithelium cells (p = 0.16) and fewer glial fibres (p = 0.08) in membranes from bevacizumab-treated eyes compared with placebo-treated eyes. Bevacizumab was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. Conclusions:, Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection. [source] Intravitreal anti-vascular endothelial growth factor therapy with bevacizumab for tuberous sclerosis with macular oedemaACTA OPHTHALMOLOGICA, Issue 3 2010Wataru Saito Abstract. Purpose:, To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC) who were treated with intravitreal bevacizumab injection. Methods:, Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. Vascular endothelial growth factor (VEGF) concentration in the vitreous fluid was measured by enzyme-linked immunosorbent assay (ELISA) in one of these patients. Results:, Patient 1: a 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars-plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema disappeared by intravitreal injection of bevacizumab. Patient 2: a 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size reduced markedly with regression of neovascularization. Conclusion:, These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC. [source] Bevacizumab as adjuvant for neovascular glaucomaACTA OPHTHALMOLOGICA, Issue 1 2010Julia Beutel Abstract. Purpose:, We aimed to evaluate the longterm effects of intraocular bevacizumab (Avastin®) injections as adjuvant treatment in patients with neovascular glaucoma. Methods:, Twenty eyes of 18 consecutive patients with secondary neovascular glaucoma caused by proliferative diabetic retinopathy (n = 7), ischaemic central retinal vein occlusion (n = 7), ischaemic ophthalmopathy (n = 2) and retinal ischaemia resulting from persistent detachment (n = 2) were treated with intraocular bevacizumab injections (1.25 mg/0.05 ml) in addition to other treatments. The main outcome measure was the change in degree of iris rubeosis. Secondary outcomes included intraocular pressure (IOP), best corrected visual acuity (BCVA) and numbers of additional interventions or antiglaucoma medications administered after injection. Results:, Mean (± standard deviation) follow-up was 67.7 ± 13.8 weeks (range 50,93 weeks). At the last follow-up, complete regression of rubeosis was detectable in five (20%) eyes, incomplete regression in seven (35%), stabilization in six (30%), and an increase in two (10%) eyes. Mean IOP was 26.0 ± 8.9 mmHg at baseline and significantly decreased to 14.75 ± 5.3 mmHg at the last follow-up visit (p = 0.000005). Mean baseline BCVA (logMAR [logarithm of the minimum angle of resolution] 1.43 ± 0.89) was stabilized during the follow-up period (logMAR 1.5 ± 0.98). Patients received an average of 2.75 injections. Additional treatments were laser photocoagulation in 13 (65%) eyes, cyclodestructive procedure in 14 (70%), cryopexy in six (30%), drainage procedures in two (10%), and vitrectomy in five (25%) eyes. Conclusions:, Bevacizumab may be beneficial as adjuvant treatment in neovascular glaucoma because of its anti-angiogenic properties and its ability to prevent establishment or progression of angular obstruction. The causative disease inducing the angiogenic process requires treatment in all cases. Antiglaucoma treatment is needed in cases of persistent elevated IOP. [source] In vitro evaluation of bevacizumab toxicity on a retinal ganglion cell lineACTA OPHTHALMOLOGICA, Issue 6 2009Rajesh K. Sharma Abstract. Purpose:, The effects of bevacizumab on cell viability and proliferation in a commonly used retinal ganglion cell line, RGC-5, were examined. Methods:, RGC-5 cells were exposed to 0.1 mg/ml, 1 mg/ml and 2 mg/ml of commercially available bevacizumab in vitro. To examine the specificity of effects, cells were also cultured with increasing and comparable concentrations of proteins (increasing the concentration of proteins in the culture media by 0.1 mg/ml, 1 mg/ml and 2 mg/ml by using additional fetal bovine serum [FBS] and bovine serum albumin [BSA]). Cell proliferation was assessed using a WST-1 kit, crystal violet staining and bromodeoxyuridine (BrdU) incorporation. Cytotoxic effects were assessed by quantifying cell numbers in proliferation-deficient RGC-5 following exposure to bevacizumab using the WST-1 kit, microscopic examination of cells stained with propidium iodide (PI) cells and flow cytometry for differential staining with PI. Results:, Bevacizumab was not toxic to RGC-5 cells in the tested concentrations. It had a stimulatory effect on cell proliferation. A stimulatory effect on proliferation was also noted when equivalent amounts of proteins from FBS or BSA were used, which suggests that bevacizumab may stimulate proliferation non-specifically by increasing the protein contents of the cell growth environment. Conclusions:, Results suggest that intravitreal injection of bevacizumab could alter the internal milieu of the eye by increasing protein concentrations to elicit functional responses in retinotypic cells. This may be especially relevant for cells outwith the control of vascular endothelial growth factor. [source] Subconjunctival injection of bevacizumab (Avastin®) for corneal neovascularizationACTA OPHTHALMOLOGICA, Issue 2009MF DE LA PAZ Purpose to study the effects of subconjunctival injection of Bevacizumab on corneal neovascularization. Methods Prospective interventional case series on 7 eyes of 7 patients who underwent subconjunctival injection with Bevacizumab. The following parameters were studied pre-op, at 1 week, 30, 60 and 90 days post-op: UCVA, BCVA, pachymetry with OCT, slit lamp examination and photographic imaging. Conjunctival impression cytology pre-op at 1 week and 9o days was done and complications were also noted. Results Pre-op diagnoses were: herpetic leucoma (4 eyes), chemical burn (2 eyes), neurotrofic keratopathy (1 eye). An informed off-label consent form prior to procedure was signed. 1.25 mg of subconjunctival Bevacizumab was injected nearest the area affected. Mean preoperative UCVA and BCVA were 0.86 and 0.44 LogMar units, improved to 0.61 and 0.26 LogMar units at 90 days post-op, respectively. Central and peripheral pachymetry improved from 532 and 623 microns pre-op, to 529 and 619 microns at 90 days post-op, respectively. All slit lamp findings and photographic imaging showed a clear regression of superficial and deep stromal corneal vascularization, with clearing of lipid deposits around the affected areas. No toxic effects were noted on conjunctival impression cytology. Conclusion Subconjunctival injection of Bevacizumab is a safe and effective procedure for the regression of superficial and deep corneal neovascularization. It may be a good alternative for patients prior to performing an optical keratoplasty or for those who are poor candidates for the same. [source] Multiple effects of bevacizumab in angiogenesis: implications for its use in age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 5 2009Angela Carneiro Abstract. Purpose:, This study aimed to elucidate the precise effects of bevacizumab in all steps in the neovascularization process in endothelial cells. Methods:, Human umbilical vein endothelial cells (HUVECs) were incubated with bevacizumab at concentrations within the clinically established range or with identical amounts of excipient. Cell cytotoxicity (evaluated by MTT assay), proliferation (by BrdU incorporation assay), apoptosis (by TUNEL assay), migration (by double-chamber assay) and vessel assembly in matrigel-coated plates were assessed in vitro. Mouse plug matrigel assays were performed to confirm in vitro results. Results:, Incubation of HUVECs with bevacizumab did not present cytotoxicity. Concentrations comparable with those after intravitreal doses of bevacizumab significantly reduced proliferation and migration capacity, and increased apoptotic rates in these cells. In addition, bevacizumab led to a significant decrease in the assembly of capillary-like structures on matrigel assay in comparison with excipient-treated cells. Further substantiating these in vitro findings, bevacizumab also inhibited angiogenesis in a mouse plug matrigel assay, as evaluated by haemoglobin content levels. Conclusions:, These results demonstrate that clinical doses of bevacizumab are able to prevent several steps of the angiogenic process. Bevacizumab is thus currently recommended for treating disorders that present augmented angiogenesis. [source] Clinical and Histological Aspects of CNV Formation: Studies in an Animal ModelACTA OPHTHALMOLOGICA, Issue thesis2 2008Nathan Lassota MD Abstract. The purpose of the present thesis was to develop an animal model of CNV in order to study the early formation of CNV and to test the effects of an anti-angiogenic treatment. Porcine eyes were chosen as a substrate for CNV induction, since they are similar to human eyes in terms of both macroscopic and microscopic morphology. However, a major difference is that pigs lack a fovea; instead they have a visual streak, with a relatively stable and high concentration of cones. By surgical perforation of Bruch's membrane we were able to induce formation of CNV membranes. The morphology and cellular composition of these membranes varied with the surgical technique employed. When RPE cells were locally removed at the time of perforation, the resulting CNV was thinner, contained fewer blood vessels and was less prone to leak on fluorescein angiography than when RPE cells were left intact at induction. The neuroretina overlying the perforation site was not damaged by any of the surgical techniques, thus allowing the subsequent retinal damage to be ascribed to the actual process of CNV formation. Using this animal model allowed us to directly map histological findings onto fluorescein angiograms and thereby perform meaningful correlations between histopathologic and photographic features. Such correlations have been hampered in human subjects, since human eyes are not enucleated as a consequence of CNV and are therefore only available for post-mortem studies. In such studies there often is a considerable time-gap between the death of the patient and the latest available fluorescein angiogram, thereby allowing macular pathology to evolve in the interim. Histological examination of the porcine membranes demonstrated that they were composed of RPE cells, glial cells, macrophages, endothelial cells, collagen and smooth muscle fibres, which are the same cellular and fibrillar elements that dominate human CNV membranes. The porcine model was applied to test the effects, in a randomized and masked fashion, of intravitreally injected bevacizumab. Bevacizumab, a pan VEGF A antibody, was found to reduce both the proliferation of endothelial cells in CNV membranes and the propensity to leak in fluorescein angiograms. Immunohistochemically, bevacizumab was detected in the inner limiting membrane, in retinal blood vessels and binding uniformly to the entire CNV membrane without any cellular predisposition. Based on the above findings we believe that the porcine CNV model shows a bearing to human disease and therefore might be used as a tool to obtain improved treatments for this debilitating condition. [source] Bevacizumab in ophthalmology: the controversy moves forwardCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 4 2010Mark C Gillies PhD FRANZCO No abstract is available for this article. [source] Avastin as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case seriesCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2008Jonathan Yeoh FRANZCO Abstract Purpose:, Bevacizumab (Avastin) is a monoclonal antibody which targets all isoforms of vascular endothelial growth factor A. Its potent anti-angiogenic effects have been shown to cause regression of neovascularization in proliferative diabetic retinopathy. The aim of this study is to investigate the role of Avastin as an adjunct to vitrectomy in the management of severe diabetic eye disease. Methods:, Sixteen patients (18 eyes) with severe proliferative diabetic retinopathy were recruited into the study. All eyes underwent a single intravitreal injection of bevacizumab 1.25 mg in 0.05 mL prior to vitrectomy surgery for the management of tractional retinal detachment or vitreous haemorrhage due to severe proliferative diabetic retinopathy. Results:, At 3 months, seven eyes had visual acuities which were better than baseline, four were unchanged and seven were worse. At 6 months, 14 eyes had visual acuities better than baseline, one was unchanged and three were worse. Seven of the 18 eyes (38.8%) had postoperative rebleeds, six of which required surgical washout. Conclusion:, Avastin improved the ease of the surgery in these complex eyes and the early results are encouraging. We have found it to be particularly useful in diabetic eyes with traction detachments of short duration in which there is still active neovascularization. [source] Bevacizumab (Avastin) for the treatment of neovascular glaucomaCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2007Michael N Chilov MBBS Abstract Herein three cases of angle closure secondary to neovascularization (elevated intraocular pressure in two of the cases) treated with the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) are reported. In all three cases there was rapid resolution of neovascularization and control of intraocular pressure. One patient with corneal anaesthesia from diabetes developed infectious keratitis, potentially as a consequence of inhibition of VEGF wound healing and neurotrophic functions. Avastin appears to have a promising role in the treatment of neovascular glaucoma but is not without potential local and systemic side-effects. [source] The current status of targeted therapy for non-small cell lung cancerINTERNAL MEDICINE JOURNAL, Issue 9 2010H. Francis Abstract Lung cancer accounts for more cancer-related deaths than any other malignancy in Australia and worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers and is associated with a 5-year survival of only 15%. Treatment with platinum-based doublets in the first-line setting and single agent chemotherapy in the second-line setting has improved survival and quality of life in patients with NSCLC. However, the benefits associated with chemotherapy are modest and serve to stress the need for novel therapeutic approaches. In the last decade a range of targeted therapies has been evaluated in NSCLC. Dramatic and often durable responses were seen in patients treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib particularly in females, non-smokers, patients of East Asian ethnicity and those with adenocarcinomas , a group subsequently found to be enriched for tumours with activating EGFR mutations. Large randomized phase III trials have since established a role for EGFR TKI in the second- and third-line setting as well as a potential role for the monoclonal antibodies bevacizumab and cetuximab, directed at vascular endothelial growth factor and EGFR, respectively, in the combination with chemotherapy in the first-line setting. Recently it has been shown that patients with EGFR mutations may benefit from gefitinib in the first-line setting. Other promising agents under evaluation are inhibitors of the insulin-like growth factor-1 receptor and inhibitors of recently described ALK gene rearrangements. [source] Effects of intravitreal bevacizumab (Avastin®) therapy on retrobulbar blood flow parameters in patients with neovascular age-related macular degenerationJOURNAL OF CLINICAL ULTRASOUND, Issue 2 2010Ahmet Mete MD Abstract Background. To investigate the effects of intravitreal bevacizumab on retrobulbar circulation in patients with neovascular age-related macular degeneration (AMD). Method. Thirty patients with neovascular age-related macular degeneration were assessed prospectively by both color Doppler imaging and fundus fluorescein angiography. Spectral Doppler analysis allowed the measurement of the maximum velocity (Vmax) and minimum velocity (Vmin) of the central retinal vein (CRV), and peak systolic (PSV), end-diastolic (EDV) velocities of blood flows, and pulsatility index (PI) and resistance index (RI) values in the central retinal artery (CRA), nasal and temporal posterior ciliary arteries (NPCA, TPCA), and ophthalmic artery (OA). The t test for paired samples was used to compare retrobulbar blood flow values before and after intravitreal bevacizumab injection. Result. PSV and EDV of the NPCA and PSV of the TPCA were significantly decreased after intravitreal bevacizumab injection (p < 0.05). There was no statistically significant difference in the other parameters. Conclusion. Our results suggest that intravitreal bevacizumab therapy has a measurable effect on retrobulbar blood flow. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2010 [source] "Spontaneous," delayed colon and rectal anastomotic complications associated with bevacizumab therapyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008David A. August MD Abstract Bevacizumab, a humanized monoclonal antibody used to treat recurrent and metastatic colorectal cancer, targets the vascular endothelial growth factor (VEGF) molecule. It is hypothesized that bevacizumab works by both depriving tumors of the neovascularity they require to grow, and by improving local delivery of chemotherapy through alterations of tumor vasculature permeability and Starling forces. Complications of bevacizumab treatment include bowel ischemia and perforation, but to date, these complications have only rarely been described as occurring at the site of presumably healed anastomoses following surgery. We report two cases of delayed, "spontaneous" low anterior colorectal anastomotic dehiscence and one right colon anastomotic colocutaneous fistula associated with bevacizumab therapy. After seeing three patients with complications arising from apparently healed low anterior colorectal or right colon anastomoses following initiation of bevacizumab therapy for treatment of metastatic colorectal cancer, we reviewed the experience of The Cancer Institute of New Jersey (CINJ) with use of bevacizumab in approximately 50 patients between April 2004 and December 2006. The three index cases had been treated surgically at CINJ but received chemotherapy elsewhere. None of the 50 patients receiving bevacizumab at CINJ who had previous colon or rectal anastomoses were identified as having this complication. The medical records of the three index cases were reviewed and analyzed. Additionally, a Medline search was performed to identify other reports documenting similar cases. Two reports of related cases were found in the literature. In two of our index cases who underwent low anterior anastomoses, the patients had received preoperative pelvic irradiation before their initial low anterior resection. In one of the two cases, the initial resection was complicated by an anastomotic leak requiring proximal diversion and then subsequent stoma takedown. In both cases, the dehiscence occurred more than 1 year after anastomosis, and became evident 1,10 months following initiation of bevacizumab treatment. In the third index case, a colocutaneous fistula arising from the anastomotic site presented 5 months following right colon resection and 3 months after starting adjuvant systemic therapy with FOLFOX (5-fluorouracil (5-FU), leucovorin, and oxaliplatin) and bevacizumab. Delayed colorectal anastomotic complications may occur in association with bevacizumab therapy. Contributing factors may include anastomotic leak at the time of the original operation and history of anastomotic irradiation. Clinicians treating patients who receive bevacizumab following colectomy for colorectal cancer should be aware of this possible life-threatening complication. These findings may also be relevant to the design of trials of the use of bevacizumab for the postoperative adjuvant treatment of patients with colorectal cancer. J. Surg. Oncol. 2008;97:180,185. © 2007 Wiley-Liss, Inc. [source] Perforating dermatosis in a patient receiving bevacizumabJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2009S Vano-Galvan [source] Venous thromboembolism in malignant gliomasJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2010E. O. JENKINS Summary., Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas. [source] Noncompartmental kinetic analysis of DCE-MRI data from malignant tumors: Application to glioblastoma treated with bevacizumabMAGNETIC RESONANCE IN MEDICINE, Issue 2 2010Ruediger E. Port Abstract Dynamic contrast enhanced MRI contrast agent kinetics in malignant tumors are typically complex, requiring multicompartment tumor models for adequate description. For consistent comparisons among tumors or among successive studies of the same tumor, we propose to estimate the total contrast agent,accessible volume fraction of tumor, including blood plasma, vpe, and an average transfer rate constant across all tumor compartments, Ktrans.av, by fitting a three-compartment tumor model and then calculating the area under the tumor impulse-response function (= vpe) and the ratio area under the tumor impulse response function over mean residence time in tumor (= Ktrans.av). If the duration of dynamic contrast enhanced MRI was too short to extrapolate the tumor impulse-response function to infinity with any confidence, then conditional parameters v and Ktrans.av* should be calculated from the available incomplete impulse response function. Median decreases of 33% were found for both v and Ktrans.av* in glioblastoma patients (n = 16) 24 hours after the administration of bevacizumab (P < 0.001). Median total contrast-enhancing tumor volume was reduced by 18% (P < 0.0001). The combined changes of tumor volume, v, and Ktrans.av* suggest a reduction of true vpe, possibly accompanied by a reduction of true Ktrans.av. The proposed method provides estimates of a scale and a shape parameter to describe contrast agent kinetics of varying complexity in a uniform way. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [source] An automated method for nonparametric kinetic analysis of clinical DCE-MRI data: Application to glioblastoma treated with bevacizumabMAGNETIC RESONANCE IN MEDICINE, Issue 5 2010Gregory Z. Ferl Abstract Here, we describe an automated nonparametric method for evaluating gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) kinetics, based on dynamic contrast-enhanced,MRI scans of glioblastoma patients taken before and after treatment with bevacizumab; no specific model or equation structure is assumed or used. Tumor and venous blood concentration-time profiles are smoothed, using a robust algorithm that removes artifacts due to patient motion, and then deconvolved, yielding an impulse response function. In addition to smoothing, robustness of the deconvolution operation is assured by excluding data that occur prior to the plasma peak; an exhaustive analysis was performed to demonstrate that exclusion of the prepeak plasma data does not significantly affect results. All analysis steps are executed by a single R script that requires blood and tumor curves as the sole input. Statistical moment analysis of the Impulse response function yields the area under the curve (AUC) and mean residence time (MRT). Comparison of deconvolution results to fitted Tofts model parameters suggests that and AUC of the Impulse response function closely approximate fractional clearance from plasma to tissue (Ktrans) and fractional interstitial volume (ve) . Intervisit variability is shown to be comparable when using the deconvolution method (11% [] and 13%[AUC]) compared to the Tofts model (14%[Ktrans] and 24%[ve]). AUC and both exhibit a statistically significant decrease (P < 0.005) 1 day after administration of bevacizumab. Magn Reson Med 63:1366,1375, 2010. © 2010 Wiley-Liss, Inc. [source] Reversible skeletal changes after treatment with bevacizumab in a child with cutaneovisceral angiomatosis with thrombocytopenia syndromePEDIATRIC BLOOD & CANCER, Issue 3 2008Angela R. Smith MD Abstract Cutaneovisceral angiomatosis with thrombocytopenia (CAT) syndrome is a rare vascular disorder of the skin and gastrointestinal tract for which there is no standard treatment. We present a case in which a child with CAT syndrome was treated with bevacizumab, a vascular endothelial growth factor inhibitor, and subsequently developed asymptomatic metaphyseal bone lesions. Though not previously described as a side effect, we hypothesize that the use of bevacizumab in a child with active epiphyseal growth plates caused these radiographic lesions. Because of the potential for altered bone growth and metabolism, children receiving VEGF inhibitors should be monitored closely for bony toxicity. Pediatr Blood Cancer 2008;51:418,420. © 2008 Wiley-Liss, Inc. [source] Hemostatic complications of angiogenesis inhibitors in cancer patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2008Francesca Elice Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets for rational drug design of antineoplastic agents. Five such agents with angiogenesis inhibiting activity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use and many others have entered clinical trials. Vascular complications, including venous or arterial thromboembolism and hemorrhage, have emerged as relevant toxicities in several clinical trials with angiogenesis inhibitors. Given the well-known interplay between the blood clotting system, angiogenesis, and tumor growth, a better understanding of the impact of these new drugs on overall hemostatic balance is required. In this brief overview, we discuss the incidence of hemostatic complications, the likely pathogenetic mechanisms involved, and the critical need to establish in randomized clinical trials the usefulness of thrombosis prophylaxis to prevent these complications. Careful documentation of hemostatic complications during treatment with each of the new antiangiogenic drugs is warranted. Further studies are urgently required to better define the causal association of these new agents with hemostatic complications and to establish the best prophylactic strategy. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecanAPMIS, Issue 8 2010Benedikte Hasselbalch Hasselbalch B, Eriksen JG, Broholm H, Christensen IJ, Grunnet K, Horsman MR, Poulsen HS, Stockhausen M-T, Lassen U. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan. APMIS 2010; 118: 585,94. Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan. Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating that they share the same regulatory mechanisms. None of the EGFR-related biomarkers showed any significant correlations with each other. None of the biomarkers tested alone or in combination could identify a patient population likely to benefit from bevacizumab and irinotecan, with or without the addition of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy. [source] New systemic treatment options for metastatic renal-cell carcinoma in the era of targeted therapiesASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Thean Hsiang TAN Abstract Advances in understanding the biology and genetics of renal-cell carcinomas have led to the development of novel targeted therapies for the treatment of metastatic renal-cell cancer. Previously the systemic approaches were limited to cytokine therapies that were modest in their clinical benefits and at the expense of significant toxicities. Investigational treatments with allogeneic bone marrow transplantation were equally toxic and resulted in significant morbidity and mortality. The development of targeted therapy has revolutionized the treatment of metastatic renal-cell cancer with more meaningful outcomes. This review aims to provide a detailed discussion of the clinical benefits of targeted therapies such as sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and some of the newer agents in clinical trial development. The efficacy of these compounds in terms of response, survival and clinical benefit are explored as well as their toxicities. The role of surgery in metastatic renal-cell carcinoma is reviewed in the context of cytoreductive therapy and resection of solitary and oligometastatic disease. Ongoing studies in the adjuvant setting following curative resection are also reviewed. The availability of targeted therapies has led to their rapid adoption as frontline therapy over traditional cytokine therapy, thus bringing more optimistic and hopeful therapeutic options in a condition where historically, systemic treatments have been relatively unsatisfactory and disappointing. [source] Spinal cord infarction in a patient with metastatic non-small cell lung cancer, receiving chemotherapy combined with bevacizumabASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Katherine MASSELOS Abstract Bevacizumab is an anti-angiogenesis agent that has many applications in the current management of patients with cancer, including advanced non-small cell lung cancer. Its value is however, not without side effects. We present the first reported case of spinal cord infarction in the setting of bevacizumab use in a 70-year old woman with advanced non-small cell lung cancer. [source] Role of novel targeted agents in the treatment of metastatic colorectal cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2007Dragan DAMIANOVICH Abstract Modern chemotherapy regimens, combining bolus or infused schedules of 5-fluorouracil (5-FU) with irinotecan or oxaliplatin, have significantly improved the treatment outcomes of patients with metastatic colorectal cancer (CRC). The addition of novel targeted agents to chemotherapy has the potential to increase the median survival of patients with metastatic CRC beyond 2 years. Bevacizumab, a monoclonal antibody (mAb) to vascular endothelial growth factor, has an established role in first-line treatment in combination with either 5-FU/leucovorin or irinotecan/5-FU/leucovorin regimens, while cetuximab, a mAb to epidermal growth factor receptor, in combination with irinotecan is more suitable for the treatment of refractory metastatic CRC. The use of bevacizumab in later stages of the disease and cetuximab in chemotherapy-naive patients as well as concurrent treatment with both agents is still under investigation. The landmark studies leading to the approval of these agents in the treatment of metastatic CRC as well as associated toxicity profiles and detailed treatment recommendations are discussed in this review. [source] Epistaxis during Treatment with PaclitaxelBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Nirit Yarom Patients who were treated with paclitaxel filled a questionnaire regarding their general health, medications and incidents of epistaxis. Relevant clinical information was obtained from the patients' charts. Forty-seven consecutive patients were recruited to the study. Twenty-four (51%) of the patients reported epistaxis during paclitaxel therapy. Twenty-three of 39 (59%) patients who received weekly paclitaxel had epistaxis at least once during treatment, compared with one out of eight patients who were treated every 3 weeks (P = 0.045). All episodes of epistaxis were mild, occurred with normal platelets counts and did not require blood product transfusions or treatment modification. The majority of the patients experienced the first episode of epistaxis on the third week of weekly paclitaxel treatment and then repeatedly throughout therapy. It is concluded that epistaxis is a common mild side-effect of weekly paclitaxel that has not been reported previously. In this trial, epistaxis did not have any major clinical consequences. However, when paclitaxel is combined with other drugs that may cause bleeding, such as bevacizumab, physicians should be alerted to the potential risk of this phenomenon. [source] The antitumor activity of NK012, an SN-38,incorporating micelle, in combination with bevacizumab against lung cancer xenograftsCANCER, Issue 19 2010Hirotsugu Kenmotsu MD Abstract BACKGROUND: It has been demonstrated that NK012, a novel 7-ethyl-10-hydroxycamptothecin (SN-38)-incorporating polymeric micelle, exerts significantly more potent antitumor activity against various human tumor xenografts than irinotecan (CPT-11) (a water-soluble prodrug of SN-38). Combination therapy of anticancer agents with bevacizumab (Bv), an anti-vascualr endothelial growth factor humanized monoclonal antibody, has more potently inhibited tumor growth than either agent alone. In the current study, the authors examined the antitumor effect of NK012 in combination with Bv against human lung cancer. METHODS: Nude mice bearing lung adenocarcinoma (PC-14 or A549 xenografts) were administered NK012 at SN-38-equivalent doses of 5 mg/kg or 30 mg/kg in combination with or without Bv at 5 mg/kg. CPT-11 at a dose of 66.7 mg/kg was administered with or without Bv at a dose of 5 mg/kg in the same experimental model. To evaluate interaction with Bv, the pharmacokinetics and microvessel density in tumors that were treated on each regimen were analyzed. RESULT: In vitro, the growth-inhibitory effect of NK012 was 50-fold more potent than that of CPT-11 and was almost equivalent to that of SN-38. In vivo studies revealed that the combination of NK012 plus Bv had significantly greater antitumor activity against human lung cancer xenografts compared with NK012 alone (PC-14, P = .0261; A549, P < .001). The pharmacokinetic profile of NK012 revealed that coadministration of Bv did not interfere with the accumulation of NK012. CONCLUSIONS: In this study, significant antitumor activity was noted with NK012 in combination with Bv against lung cancer cells. The current results warrant the clinical evaluation of NK012 in lung cancer. Cancer 2010. © 2010 American Cancer Society. [source] |