Short-term intraocular pressure changes after intravitreal injection of bevacizumab in diabetic retinopathy patients

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Farhood QK

2014-03-01

Full Text Available Qasim Kadhim Farhood,1 Sinan Mohammad Twfeeq21College of Medicine, Babylon University, Babylon; 2Al-Jumhori teaching hospital, Mosul, IraqBackground: This study examined the changes in short-term intraocular pressure (IOP in a prospective series of patients undergoing intravitreal bevacizumab injection. The aim was to evaluate the frequency and predictive factors related to intraocular pressure (IOP elevation in patients receiving intravitreal bevacizumab.Patients and methods: This study included 52 patients with diabetic retinopathy between 28 to 75 years of age with a mean age of 51 years; 30 (58% were females, and 22 (42% were males. All patients received bevacizumab (1.25 mg/0.05 mL injected intravitreally in a standard fashion between May 2012 to February 2013 in the AL-Jumhoury teaching hospital. IOP was measured at baseline, 5, 10, and 30 minutes after injection using Goldman applanation tonometry.Statistics: Data were analyzed using the SPSS v.12.0 for windows. Basic, demographic, and clinical data were analyzed using means, proportions, and appropriate 95% confidence intervals (CIs.Results: Most patients (85% were diagnosed with proliferative diabetic retinopathy, while 15% presented with diabetic macular edema. The mean IOP values at baseline, 5, 10, and 30 minutes after injection were 14.0 mmHg (95% CI 13.4–14.7, 36.1 mmHg (95% CI 33.5–38.6, 25.7 mmHg (95% CI 23.8–27.5, and 15.5 mmHg (95% CI 12.4–16.51, respectively. Regression analysis showed a trend toward phakic patients having higher IOP at 30 minutes.Conclusion: Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all IOP returned to a safe range (<25 mmHg within 30 minutes. Elevated IOP 30 minutes after injection only occurs rarely, so routine prophylactic use of anti-glaucoma medication is not indicated.Keywords: intravitreal injection, bevacizumab, intraocular pressure, Goldmann applanation tonometry

Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

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Sean D. Adrean

2017-01-01

Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

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Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

2016-01-01

Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevac......Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...

Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

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Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

2012-01-01

Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

Therapeutic significance of a D-dimer cut-off level of >3 μg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

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Mochizuki, Satoshi; Yoshino, Takayuki; Kojima, Takashi

2010-01-01

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 μg/ml. The appropriate D-dimer cut-off level was 3 μg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 μg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 μg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 μg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy. (author)

Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

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Boutsikou E

2013-03-01

Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy.

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Goede, V; Coutelle, O; Neuneier, J; Reinacher-Schick, A; Schnell, R; Koslowsky, T C; Weihrauch, M R; Cremer, B; Kashkar, H; Odenthal, M; Augustin, H G; Schmiegel, W; Hallek, M; Hacker, U T

2010-10-26

The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; Panti-angiogenic treatment.

Therapeutical evaluation of bevacizumab application in relapsed pterygium

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Mayara Martins Abrahão

Full Text Available Abstract Objective: Therapeutic evaluation of Bevacizumab application in relapsed pterygium concerning visual acuity, keratometry, refraction, symptomatology. Methods: Group 1 (4 patients received 0.1 ml of Bevacizumab (avastin, being evaluated posteriorly on the tenth and thirtieth days after the application, seeking to compare with the exam previously made, being it realized with the other two groups, in which Group 2 (4 patients received 0.2 ml of Bevacizumab and the Group 3 (3 patients received 1 ml of the placebo injection. Results: In this study, eleven eyes of eleven patients were evaluated. Among these patients, 7 were women (63.6% and 4 men (36.4%. There was a variation in the cylindrical diopter after the treatment with a dose of 0.1 ml of bevaciumab during the evaluation on the thirtieth day. Whereas the cylindrical shaft had a significantly larger modification after the application of 0.2 ml. Regarding the spherical diopter variation, there were modifications in the 3 groups. The keratometry varied in the 3 groups, mostly after the thirtieth day of evaluation. In relation to symptomatology, it was observed a reduction in the subjective evaluation of the eye burning sensation, the prurience mentioned by the patient and a reduction of the hyperemia biomicroscopy evaluation. Conclusion: In bevacizumab application in the recurrent pterygium treatment, there is modification of the spherical and cylindrical parameters of refraction, besides the changes in keratometry and the reduction of the symptomatology.

Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

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Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

2011-01-01

Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

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Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed [Brown University Oncology Group, Providence, RI (United States); Safran, Howard, E-mail: hsafran@lifespan.org [Brown University Oncology Group, Providence, RI (United States)

2012-01-01

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

Reversal of cerebral radiation necrosis with bevacizumab treatment in 17 Chinese patients

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Wang Yang

2012-08-01

Full Text Available Abstract Background Bevacizumab has been suggested as a new treatment modality for cerebral radiation necrosis due to its ability to block the effects of vascular endothelial growth factor (VEGF in leakage-prone capillaries, though its use still remains controversial in clinical practice. Methods The use of bevacizumab in 17 patients with symptomatic cerebral radiation necrosis poorly controlled with dexamethasone steroid treatments was examined between March 2010 and January 2012. Bevacizumab therapy was administered for a minimum of two cycles (7.5 mg/kg, at two-week interval with a median of four bevacizumab injections. Changes in bi-dimensional measurements of the largest radiation necrosis lesions were observed by gadolinium-enhanced and T2-weighted magnetic resonance imaging (MRI. Additionally, dexamethasone dosage, Karnofsky performance status (KPS, adverse event occurrence and associated clinical outcomes were recorded for each patient. Results MRI analysis revealed that the average reduction was 54.9% and 48.4% in post-gadolinium and T2-weighted sequence analysis, respectively. Significant clinical neurological improvements were expressed in 10 patients according to KPS values. Dexamethasone reduction was achieved four weeks after initiation of bevacizumab in all patients, with four patients successfully discontinuing dexamethasone treatment. Mild to moderate bevacizumab-related adverse events, such as fatigue, proteinuria and hypertension were observed in three patients. Upon follow-up at 4 to 12 months, 10 patients showed clinical improvement, and 7 patient deaths occurred from tumor progression (5 patients, recurrent necrosis (1 patient, and uncontrolled necrosis-induced edema (1 patient. Conclusions These findings suggest bevacizumab as a promising treatment for cerebral radiation necrosis induced by common radiation therapies, including external beam radiotherapy (EBRT, stereotactic radiosurgery (SRS, and fractionated stereotactic

Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

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Gutin, Philip H.; Iwamoto, Fabio M.; Beal, Kathryn; Mohile, Nimish A.; Karimi, Sasan; Hou, Bob L.; Lymberis, Stella; Yamada, Yoshiya; Chang, Jenghwa

2009-01-01

Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.

Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

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Jakobsen, J N; Urup, T; Grunnet, K

2018-01-01

The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination...... therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been......-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision...

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

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Lister J

2012-10-01

Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

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Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

2013-12-01

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

Managed hypertensive crisis induced by bevacizumab in patient with metastatic lung adenocarcinoma

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Gracova, K.; Dolakova, L.

2015-01-01

Purpose and objective: The aim of the casuistry is to present a case report of a patient with metastatic lung adenocarcinoma and describe the successful management of hypertensive crisis, which is one of the most common cardiovascular complications of bevacizumab therapy. Casuistry: We describe 82-year old patient with lung adenocarcinoma verified by cytology of fluidothorax. Patient started chemotherapy in the scheme of carboplatin + paclitaxel with addition of bevacizumab since the third cycle. We provided a CT-scan which described partial tumour regression after six cycles of chemotherapy and four cycles of bevacizumab. Before the first cycle of maintenance therapy with bevacizumab patient overcame hypertensive crisis with neurological symptomatology which reacted positively to standard antihypertensives added to the therapy. After the stabilization we continued oncological treatment until disease progression and post chemotherapeutic ischemic colitis occurrence. Conclusion: Arterial hypertension is a common adverse effect of treatment with VEGF inhibitors. Considering the fact that the hypertension may occur at any time during the treatment with bevacizumab, blood pressure should be measured before, during and after the infusion. This side effect is reversible. On the basis of several case studies a positive association between arterial hypertension and prolonged survival in cancer patients has been found, as a difference from those without arterial hypertension during the treatment. Antihypertensive treatment does not reduce the antitumor effect of bevacizumab treatment. (author)

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

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Suenaga M

2015-01-01

Full Text Available Mitsukuni Suenaga, Nobuyuki Mizunuma, Eiji Shinozaki, Satoshi Matsusaka, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev. We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.Methods: Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E, thrombus >40 mm in diameter (S, thrombus involving the superior vena cava (C, and decreased blood flow (V.Results: Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9% by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%. Of these 56 patients, 11 (19.6% received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%, as well as V in two (18.2%, S + V + C in one (9.1%, E + S + V in one (9.1%, E + C in one (9.1%, E in one (9.1%, and C in one (9.1%. All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%. Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%, but there were no treatment

An Association between Bevacizumab and Recurrent Posterior Reversible Encephalopathy Syndrome in a Patient Presenting with Deep Vein Thrombosis: A Case Report and Review of the Literature

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Mark Lazarus

2012-01-01

Full Text Available Background. The posterior reversible encephalopathy syndrome (PRES is a syndrome characterized by hypertension, headache, seizures, and visual disturbances. Causes of PRES include preeclampsia/eclampsia, hypertension, and recently bevacizumab, a monoclonal antibody vascular endothelial growth factor (VEGF inhibitor. There is no information to date about PRES recurrence in patients taking bevacizumab or descriptions of deep vein thrombosis (DVT in the setting of PRES. We reviewed data on a patient receiving bevacizumab who presented with a DVT and PRES and later developed recurrent PRES. Case. A 72-year-old man with metastatic pulmonary adenocarcinoma received maintenance bevacizumab following six cycles of carboplatin and paclitaxel. Following his eighth dose of bevacizumab, he developed a DVT as well as PRES. He made a rapid recovery and was discharged from the hospital but went on to develop PRES recurrence nine days following his original episode. Conclusion. Several mechanisms exist whereby exposure to bevacizumab could be related to the development of both DVT and PRES by inducing global endothelial dysfunction. Recurrent PRES may result from bevacizumab’s prolonged half-life (11–50 days and suboptimal blood pressure control. In the setting of bevacizumab, PRES surveillance may play a similar role in preeclampsia screening as both diseases share similar antiangiogenic signaling pathways.

Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

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Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

2013-01-01

standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

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Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

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Di Bartolomeo M

2015-01-01

Full Text Available Maria Di Bartolomeo,1 Claudia Maggi,1 Francesca Ricchini,1 Filippo Pietrantonio,1 Roberto Iacovelli,1 Filippo de Braud,1 Alessandro Inno2 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 2Department of Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy Abstract: Metastatic colorectal cancer (mCRC, like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a ­historical conservative approach. Keywords: bevacizumab, elderly, metastatic colorectal cancer, antivascular treatment, review

First-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer : analysis of the Italian patients enrolled in the SAiL study.

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Bearz, Alessandra; Passalacqua, Rodolfo; Alabiso, Oscar; Cinieri, Saverio; Gridelli, Cesare; Cravesana, Claudia; Crinò, Lucio

2012-11-01

First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

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Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

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Chapman, Suzannah J; McKavanagh, Daniel; Burge, Matthew E; McPherson, Ian; Walpole, Euan; Hollingworth, Samantha A

2017-10-01

Metastatic colorectal cancer has a large burden of disease in Australia. Medical therapy is fundamental to extending survival and improving quality of life. The benefits of two costly medicines, bevacizumab and cetuximab, used in Australia remain unclear. The aim of this study was to retrospectively examine the use of these two medicines in metastatic colorectal cancer across five public hospitals in south east Queensland and to compare clinical outcomes to those of published clinical trials. We extracted data from the chemotherapy prescribing database for patients planned for bevacizumab or cetuximab therapy between 2009 and 2013. Median overall survival was estimated using Kaplan-Meier methods. There were 490 bevacizumab-containing protocols planned and 292 patients received at least one dose of bevacizumab. Median overall survival was 17.2 months (95% confidence interval [CI], 15.4-19.3). Of 208 planned cetuximab-containing protocols, 134 patients received at least one dose of cetuximab. Median overall survival was 9.1 months (95% CI, 7.6-12.0). Thirty-day mortality rates from date of first dose were 0.7% for bevacizumab and 7.5% for cetuximab. Overall survival of patients receiving bevacizumab and cetuximab was consistent with clinical trials, providing some assurance that benefits seen in trials are observed in usual practice. This study provides a methodology of using routinely collected health data for clinical monitoring and research. Because of the high cost of these medicines and the lack of toxicity data in this study, further analysis in the postmarketing setting should be explored. © 2016 John Wiley & Sons Australia, Ltd.

Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

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Xiao ZHAO

2012-01-01

Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases

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Francesco Erovigni

2016-10-01

Full Text Available Medication-induced Osteonecrosis of the Jaw (MRONJ has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab, but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively. We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.

Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

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Deli Krizova

2014-01-01

Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

Abdominal wall perforation in a patient with recurrent epithelial ovarian cancer after bevacizumab treatment

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Efnan Algin

2016-08-01

Full Text Available Bowel perforation is a rare but well-described complication of bevacizumab, a VEGF monoclonal antibody. However, bevacizumab associated abdominal wall perforation is a more serious complication. In here, a patient with recurrent epithelial ovarian cancer developing both bowel and abdominal wall perforation after bevacizumab treatment is reported with review of the literature to point out the clinical significance of this rare complication. To our knowledge, this is the first case with bevacizumab associated abdominal wall perforation.

Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer

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Yang Q

2015-09-01

Full Text Available Qiong Yang,1–4,* Chenxi Yin,1,3,4,* Fangxin Liao,1,3,4 Yuanyuan Huang,1,3,4 Wenzhuo He,1,3,4 Chang Jiang,1,3,4 Guifang Guo,1,3,4 Bei Zhang,1,3,4 Liangping Xia1,3,41VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workBackground: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%, 22 stable disease responses (62.9%, and six progressive disease responses (17.1% were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7–48.0 months, the median progression-free survival was 5.98 months (95% confidence interval: 4.76–7.2 months, and the median overall survival was 14.77 months (95% confidence interval: 11.45–18.1 months. In the univariate analysis

Role of bevacizumab in uterine leiomyosarcoma.

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Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

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Reyin Lien

Full Text Available The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB for the treatment of retinopathy of prematurity (ROP up to the age of 2 years.The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028 and psychomotor (p = 0.002 impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041. The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

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Songliang ZHANG

2015-06-01

Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

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Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

2013-01-01

BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

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Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

2018-04-18

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

INTEGRATION OF BEVACIZUMAB IN METASTATIC COLORECTAL CANCER CHEMOTHERAPY REGIMENS IN 2 CLINICAL CENTERS IN MOSCOW AND SAINT PETERSBURG

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N. V. Dobrova

2013-01-01

Full Text Available The aim of this study was to estimate efficacy of first line chemotherapy with bevacizumab in metastatic colorectal cancer patients and investigate the impact of different prognostic factors on treatment outcome.Methods.During 2004–2008 48 colorectal cancer patients were included (29 in Russian N.N. Blokhin Cancer Research Center, 19 in St. Petersburg, who had unresectable distant metastases. Primary tumor was resected in 93.8 % patients. 52.1 % had rectal cancer. 87.5 % had liver metastases, 43.8 % had more than 1 organ affected. 66.7 % received chemotherapy with bevacizumab 5 mg/kg biweekly, 33.3 % received bevacizumab 7,5 mg/kg every 3 weeks. 62.5 % patients had oxaliplatin-based regimens, 35.4 % – only fluorpyrimidines, 2.1 % – chemotherapy with irinotecan.Results.Median time of bevacizumab use was 7.8 months. 60.3 % had objective response, 87.4 % had stable diseases during more than 6 months. Median progression-free survival (PFS was 11.5 months. Median overall survival (OS was 24.1 months.Conclusions.Survival and efficacy results are comparable to international experience. Combination of fluorpyrimidines with bevacizumab had comparable efficacy to combined chemotherapy regimens with no impact on quality of life. Integration of bevacizumab in combined treatment regimens reduced the impact of negative prognostic factors on PFS and OS. 

The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer.

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Silwal-Pandit, Laxmi; Nord, Silje; von der Lippe Gythfeldt, Hedda; Møller, Elen K; Fleischer, Thomas; Rødland, Einar; Krohn, Marit; Borgen, Elin; Garred, Øystein; Olsen, Tone; Vu, Phuong; Skjerven, Helle; Fangberget, Anne; Holmen, Marit M; Schlitchting, Ellen; Wille, Elisabeth; Nordberg Stokke, Mette; Moen Vollan, Hans Kristian; Kristensen, Vessela; Langerød, Anita; Lundgren, Steinar; Wist, Erik; Naume, Bjørn; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Engebraaten, Olav

2017-08-15

Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor-positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor-positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

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Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

2018-02-01

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

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Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

2016-11-01

Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m 2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2

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Alanin, Mikkel Christian; Klausen, Camilla; Caye-Thomasen, Per

2015-01-01

-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported...... been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg...

Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.

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Shah, Manish A; Jhawer, Minaxi; Ilson, David H; Lefkowitz, Robert A; Robinson, Edric; Capanu, Marinela; Kelsen, David P

2011-03-01

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients Who Visited Feiz Hospital during 2014–2015 Period

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Akhlaghi, Mohamad Reza; Nasrollahi, Cobra; Namgar, Seyed Mohamad; Kianersi, Farzan; Dehghani, Ali Reza; Arefpour, Reza

2017-01-01

Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC). Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA). Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg) and the rest of them did not receive any treatment (control group). The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481). There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557). A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001); however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338). Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects. PMID:29142888

Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

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Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

2017-01-01

Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response...... and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

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

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Berger, Martin D; Stintzing, Sebastian; Heinemann, Volker; Cao, Shu; Yang, Dongyun; Sunakawa, Yu; Matsusaka, Satoshi; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Schirripa, Marta; Hanna, Diana L; Soni, Shivani; Puccini, Alberto; Zhang, Wu; Cremolini, Chiara; Falcone, Alfredo; Loupakis, Fotios; Lenz, Heinz-Josef

2018-02-15

Purpose: 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. Experimental Design: 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 ( GC, CYP24A1, CYP27B1, VDR, DKK1, CST5 ) were analyzed. Results: In the discovery cohort, AA carriers of the GC 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 ( P = 0.001) and multivariable analyses ( P = 0.047). This association was confirmed in the validation cohort in multivariable analysis (OS 18.1 vs. 26.2 months, HR, 1.83; P = 0.037). Interestingly, AA carriers in the control set exhibited a longer OS (48.0 vs. 25.2 months, HR, 0.50; P = 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 ( P = 0.033) and multivariable analyses ( P = 0.046). Conclusions: GC 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. Clin Cancer Res; 24(4); 784-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study.

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Vandewalle, Evelien; Abegão Pinto, Luís; Van Bergen, Tine; Spielberg, Leigh; Fieuws, Steffen; Moons, Lieve; Spileers, Werner; Zeyen, Thierry; Stalmans, Ingeborg

2014-01-01

To investigate the efficacy and safety of a single intracameral bevacizumab injection to improve the outcome of trabeculectomy. A 12-month, prospective, randomised, double-masked, placebo-controlled trial. Patients with medically uncontrolled open-angle glaucoma scheduled for a primary trabeculectomy were recruited and randomised to receive 50 µL of either bevacizumab (1.25 mg) or placebo (balanced salt solution) peroperatively. Absolute success was defined as intraocular pressure (IOP) ≤18 mm Hg and >5 mm Hg with at least 30% reduction from baseline and no loss of light perception. Success through the use of additional medical and/or surgical IOP-lowering treatments was defined as qualified success. 138 patients completed a 12-month follow-up, 69 of whom were in the bevacizumab treated group. IOP at 1 year postoperatively was significantly lower than baseline (placebo: 25.6±9.9 mm Hg vs 11.5±3.9 mm Hg, p<0.01; bevacizumab: 24.8±8.1 mm Hg vs 11.9±3.8 mm Hg, p<0.01), with no difference between treatment groups (p=0.69). However, absolute success was higher in the bevacizumab group (71% vs 51%, p=0.02), with the need for IOP-lowering interventions (needlings) being lower in this group (12% vs 33%, p=0.003). Complication rates were low and comparable between groups. Peroperative administration of intracameral bevacizumab significantly reduces the need for additional interventions during the follow-up of patients undergoing trabeculectomy.

Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

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Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin

2010-01-01

PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow...

Bevacizumab Demonstrates Prolonged Disease Stabilization in Patients with Heavily Pretreated Metastatic Renal Cell Carcinoma: A Case Series and Review of the Literature

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Nicole M. Agostino

2010-01-01

Full Text Available There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC. These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR, such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.

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Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-09-18

Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more

Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

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Traina, Tiffany A; Rugo, Hope S; Caravelli, James F; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E; Park, John W; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D; Norton, Larry; Hudis, Clifford A; Dickler, Maura N

2010-02-01

Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months. Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

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SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

2016-01-01

The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation.

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Batman, Cosar; Ozdamar, Yasemin

2010-01-01

To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. Copyright 2010, SLACK Incorporated.

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients who Visited Feiz Hospital during 2014–2015 Period

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Mohamad Reza Akhlaghi

2017-01-01

Full Text Available Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC. Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with <1-month disease history were examined. Initially, all the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA. Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg and the rest of them did not receive any treatment (control group. The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P < 0.05. Results: In the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481. There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557. A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001; however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338. Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects.

Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial.

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Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Fargeton, Anne-Emmanuelle; Roux, Adeline; Bréant, Valentine; Colombet, Bettina; Rivière, Sophie; Cartier, César; Lacombe, Pascal; Chinet, Thierry; Blivet, Sandra; Blondel, Jean-Hugues; Gilbert-Dussardier, Brigitte; Dufour, Xavier; Michel, Justin; Harle, Jean-Robert; Dessi, Patrick; Faure, Frédéric

2016-09-06

Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated. To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT. Randomized, multicenter, placebo-controlled, phase 2/3 clinical trial with dose selection at an intermediate analysis and prespecified stopping rules (nonbinding stopping for futility). Patients aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014 to January 2015 with a 6-month follow-up after the end of treatment. Participants had a history of self-reported nosebleeds with a monthly duration of more than 20 minutes in at least the 3 months prior to inclusion corroborated by epistaxis grids completed during the same preinclusion period. Eighty consecutive HHT patients were randomized and treated in the phase 2 study, with 4 parallel groups in a 1:1:1:1 ratio. One group received placebo (n = 21); the other 3 received bevacizumab nasal spray. Each bevacizumab group received a different dose of the drug (25 mg [n = 20], 50 mg [n = 20], or 75 mg [n = 19] per treatment) in 3 doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75 mg, 150 mg, and 225 mg in each treatment group. Mean monthly epistaxis duration for 3 consecutive months immediately after the end of the treatment. Of the 80 patients who were randomized (mean age, 60.47 [SD, 10.61] years; 37 women [46.25%]), 75 completed the study. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 59 patients receiving bevacizumab in comparison with the placebo group (P = .57) or between the bevacizumab groups

Bevacizumab in the treatment of NSCLC: patient selection and perspectives

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Russo AE

2017-12-01

Full Text Available Alessia E Russo,1 Domenico Priolo,1 Giovanna Antonelli,1 Massimo Libra,2 James A McCubrey,3 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina (Messina, Italy; 2Laboratory of Translational Oncology & Functional Genomics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA Abstract: Non-small-cell lung cancer (NSCLC represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis. Bevacizumab (bev; Avastin® is a recombinant humanized monoclonal antibody that neutralizes VEGF’s biologic activity through a steric blocking of its binding with VEGF receptor. Currently, bev is the only antiangiogenic agent approved for the first-line treatment of advanced or recurrent nonsquamous NSCLC in “bev-eligible” patients. The ineligibility to receive bev is related to its toxicity. In the pivotal trials of bev in NSCLC, fatal bleeding events including pulmonary hemorrhage were observed with rates higher in the chemotherapy-plus-bev group. Therefore, in order to reduce the incidence of severe pulmonary hemorrhage, numerous exclusion criteria have been characteristically applied for bev such as central tumor localization or tumor cavitation, use of anticoagulant therapy, presence of brain metastases, age of patients (elderly. Subsequent studies designed to evaluate the safety of bev have demonstrated that this agent is safe and

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

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Abdel Kader Y

2013-07-01

Full Text Available Yasser Abdel Kader,1 Thierry Le Chevalier,2 Tamer El-Nahas,1 Amr Sakr11Department of Clinical Oncology, Cairo University, Cairo, Egypt; 2Department of Medical Oncology, Institut Gustave Roussy, Villejuif, Paris, FrancePurpose: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients.Patients and methods: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m2 on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks.Results: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III–IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06, DVT (P = 0.23, proteinuria (P = 0.23, and hypertension (P = 0.11, as well as Grade II alopecia (P = 0.001; however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66, hematological toxicity, febrile neutropenia (P = 1 and fatigue (P = 0.66. Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978. Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89.Conclusion: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy

Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.

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Shah, Manish A; Ramanathan, Ramesh K; Ilson, David H; Levnor, Alissa; D'Adamo, David; O'Reilly, Eileen; Tse, Archie; Trocola, Robin; Schwartz, Lawrence; Capanu, Marinela; Schwartz, Gary K; Kelsen, David P

2006-11-20

Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

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Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

Restriction spectrum imaging of bevacizumab-related necrosis in a patient with GBM

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Nikdokht eFarid

2013-09-01

Full Text Available Importance:With the increasing use of antiangiogenic agents in the treatment of high grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations:We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI, an advanced diffusion-weighted imaging (DWI technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.Conclusions and Relevance:Our report increases the number of pathologically-proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

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Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

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Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

2016-04-01

The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect. © 2015 UICC.

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

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Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

2015-06-01

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

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Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

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Avallone, Antonio; Piccirillo, Maria Carmela; Aloj, Luigi; Nasti, Guglielmo; Delrio, Paolo; Izzo, Francesco; Di Gennaro, Elena; Tatangelo, Fabiana; Granata, Vincenza; Cavalcanti, Ernesta; Maiolino, Piera; Bianco, Francesco; Aprea, Pasquale; De Bellis, Mario; Pecori, Biagio; Rosati, Gerardo; Carlomagno, Chiara; Bertolini, Alessandro; Gallo, Ciro; Romano, Carmela; Leone, Alessandra; Caracò, Corradina; de Lutio di Castelguidone, Elisabetta; Daniele, Gennaro; Catalano, Orlando; Botti, Gerardo; Petrillo, Antonella; Romano, Giovanni M; Iaffaioli, Vincenzo R; Lastoria, Secondo; Perrone, Francesco; Budillon, Alfredo

2016-02-08

Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Overall this

Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab

DEFF Research Database (Denmark)

Eefsen, Rikke Løvendahl; Engelholm, Lars Henning; Willemoe, Gro L.

2016-01-01

with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy......The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing...... treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell...

Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study.

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A M E Schauwvlieghe

Full Text Available To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD.Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters.Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA score between 20 and 78 letters on an EDTRS like chart in the study eye.Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed.Primary outcome was the change in BCVA in the study eye from baseline to 12 months.The mean gain in BCVA was 5.1 (±14.1 letters in the bevacizumab group (n = 161 and 6.4 (±12.2 letters in the ranibizumab group (n = 166 (p = 0.37. The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038. No significant differences in absolute CRT and CRT change (p = 0.13 or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal differed significantly (p = 0.020, with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively.Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both

Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

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Yamamoto D

2012-09-01

Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

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Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

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Qi Quan

2017-04-01

Full Text Available PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS and progression-free survival (PFS were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001 and PFS (P < .001 than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001 and PFS (P = .001. PFS (P < .001 in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049. CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

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Dellas, Kathrin; Dunst, Jürgen; Höhler, Thomas; Reese, Thomas; Würschmidt, Florian; Engel, Erik; Rödel, Claus; Wagner, Wolfgang; Richter, Michael; Arnold, Dirk

2013-01-01

Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m 2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m 2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection

Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

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Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

2011-01-01

The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

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Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

2017-12-01

To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

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Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

Advantages and Disadvantages of Combined Chemotherapy with Carmustine Wafer and Bevacizumab in Patients with Newly Diagnosed Glioblastoma: A Single-Institutional Experience.

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Akiyama, Yukinori; Kimura, Yuusuke; Enatsu, Rei; Mikami, Takeshi; Wanibuchi, Masahiko; Mikuni, Nobuhiro

2018-05-01

To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016. Twenty-five patients who underwent resection without BCNU implantation between 2010 and 2012 were enrolled as a control group; these patients were treated with the Stupp regimen and did not receive bevacizumab. This retrospective study included evaluation of progression-free survival and overall survival, plus comparisons between the combined therapy group and the control group. There were no significant differences in age, sex, Karnofsky Performance Status on admission, isocitrate dehydrogenase 1/2 mutation ratio, or resection rate between the combined and standard therapy groups. The median overall survival in the combined therapy group and control group was 24.2 months and 15.30, respectively (P = 0.027). The median progression-free survival was 16.8 months and 7.30 months, respectively (P = 0.009). Overall, the incidence of adverse events leading to discontinuation of the study drug was similar between the treatment groups, except for infection, which was more common in the combined treatment group and required repeat surgery. The combined therapy showed higher efficacy compared with standard therapy in patients with GBM. Therefore, combined therapy seems to be effective with an acceptable toxicity profile. Copyright © 2018 Elsevier Inc. All rights reserved.

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

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Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

2014-05-01

Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (SAiL study. No new safety signals were reported.

Bevacizumab Injection in Patients with Age-Related Macular Degeneration Associated with Poor Initial Visual Acuity

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Leila El Matri

2012-01-01

Full Text Available Purpose. To evaluate functional and anatomic effects of intravitreal bevacizumab in patients with neovascular AMD and initial low visual acuity. Methods. Retrospective case series of 38 eyes with neovascular AMD and initial visual acuity of 20/200 or less, treated with intravitreal bevacizumab injection. Results. Mean followup was 14.1 months ±7.1 (range: 5 to 24 months. Mean logMAR vision at baseline was 1.38 logMAR ±0.33, at 6 months was 1.14 logMAR ±0.37 (=0.001 and at 12 months was 1.22 logMar ±0.33 (=0.004. Mean baseline central retinal thickness was 431 μm ±159.7 at 6 months was 293.43 μm  ±122.79 (=10−4 and at 12 months was 293.1 μm  ±130 (=0.004. Visual acuity improved in both patients with or without prior PDT treatment. Conclusions. Intravitreal bevacizumab injection may increase the chance of visual acuity gain in neovascular AMD even in cases with initial low visual acuity.

Fibrous membranes in diabetic retinopathy and bevacizumab.

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Pattwell, David M; Stappler, Theodor; Sheridan, Carl; Heimann, Heinrich; Gibran, Syed K; Wong, David; Hiscott, Paul

2010-01-01

The purpose of this study was to determine the histopathologic characteristics of bevacizumab-treated human proliferative diabetic retinopathy (PDR) membranes with particular regard to membrane vasculature as a step toward addressing the effects of the drug on PDR membranes. Intravitreous injection of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, has recently been advocated as an adjunct in surgery for PDR. In this context, a clinically observed decrease in PDR epiretinal membrane vascularity (vascular regression) occurs from 24 hours to 48 hours after injection, but the exact mechanisms of drug action are unknown. A consecutive series of seven PDR membrane specimens that had been removed sequentially from seven bevacizumab-treated patients were studied retrospectively. The membrane specimens were examined using light microscopic methods, including immunohistochemistry. Five of the seven membranes were clinically avascular (one contained "ghost" vessels) and did not hemorrhage during excision. Of these 5 specimens, which included 1 removed 7 days after a total of 6 intravitreous injections of 1.25 mg bevacizumab, 4 contained histologically detectable capillaries (1 did not). These blood vessels were lined by endothelial cells as determined by immunohistochemistry for the endothelial markers CD31 and CD34. The two remaining membranes were clinically and histologically still vascularized despite bevacizumab treatment. All the specimens also contained smooth muscle actin-containing fibroblastic cells within the collagenous stroma. The findings do not support the concept that the clinical phenomenon of vascular regression in PDR membranes after bevacizumab injection in the vitreous is resulting from obliteration of the membrane blood vessels. Another mechanism appears to be involved in at least some patients, possibly a vasoconstrictive response. Such a mechanism might explain reversal of the effects of bevacizumab that has been reported

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

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Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Front-line Bevacizumab in combination with Oxaliplatin, Leucovorin and 5-Fluorouracil (FOLFOX in patients with metastatic colorectal cancer: a multicenter phase II study

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Touroutoglou Nikolaos

2007-05-01

Full Text Available Abstract Purpose To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC. Patients and Methods Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d1, oxaliplatin (85 mg/m2 on d1, leucovorin (200 mg/m2 on days 1 and 2 and 5-Fluorouracil (400 mg/m2 as i.v. bolus and 600 mg/m2 as 22 h i.v. continuous infusion on days 1 and 2 every 2 weeks. Results Fifty three patients (46 with a PS 0–1 were enrolled. Complete and partial response was achieved in eight (15.1% and 28 (52.8% patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%–92%; 11 (20.7% patients had stable disease and six (11.3% progressive disease. With a median follow up period of 13.5 months, time to tumor progression was 11 months while the median survival has not yet been reached; the probability of 1-, 2- and 3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed during the follow up period. Eight (15% patients underwent metastasectomy with R0 resections. Grade 3–4 neutropenia occurred in 15.1% of patients and one (1.9% of them presented febrile neutropenia. Non-hematologic toxicity included grade 3 diarrhea (7.6% and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients, respectively. One (1.9% patient presented pulmonary embolism and one (1.9% cardiac ischaemia. There was one (1.9% sudden death after the first cycle. Conclusion The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.

Effect of bevacizumab on radiation necrosis of the brain

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Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A.

2007-01-01

Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% (±22 SD), and the average change in the FLAIR images was 60% (±18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg (±3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment

Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

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Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

2017-12-01

Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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Villegas VM

2014-05-01

Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

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Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

2016-01-01

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

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Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

2009-01-01

The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy

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Freiberg FJ

2013-06-01

Full Text Available Florentina Joyce Freiberg,1 Juliane Matlach,1 Franz Grehn,1 Sabine Karl,2 Thomas Klink1 1Department of Ophthalmology, Julius Maximilian University, Wuerzburg, Germany; 2Institute of Mathematics, University of Wuerzburg, Wuerzburg, Germany Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61 who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months. Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0–15 (mean ± standard deviation and range, respectively 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12 (mean ± standard deviation and range, respectively 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005. There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU, yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008. No significant difference in best corrected visual acuity (P = 0.852 and visual field testing (P = 0.610 between preoperative to last follow

Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer.

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Tappenden, P; Jones, R; Paisley, S; Carroll, C

2007-03-01

/4 adverse events. The independent health economic assessment suggests that the cost-effectiveness of bevacizumab plus IFL is unlikely to be better than pound 46,853 per life-year gained (LYG); the cost-utility of bevacizumab plus IFL is unlikely to be better than pound 62,857 per quality-adjusted life-year (QALY) gained. The cost-effectiveness of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 84,607 per LYG; the cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. A Phase II trial reported a median OS duration of 8.6 months for patients receiving cetuximab plus irinotecan, plus a median time to progression of 4.1 months, a tumour response rate of 22.9% and suggested that treatment with cetuximab in combination with irinotecan is associated with significantly more adverse events (any grade 3 or grade 4 adverse event) than cetuximab monotherapy. The single arm study of cetuximab plus irinotecan reported a median OS duration of 8.4 months, a median time to progression of 2.9 months and a tumour response rate of 15.2%. The cost-effectiveness model suggested that the expected survival duration of patients receiving cetuximab plus irinotecan is 0.79 years (9.5 months) when the proposed continuation rule is applied. In order for cetuximab plus irinotecan to achieve a cost-utility ratio of pound 30,000 per QALY gained, treatment with cetuximab plus irinotecan must provide an additional 0.65 life years (7.8 months) over treatment with active/best supportive care, implying that survival in the active/best supportive care group must be 0.14 life years (1.7 months) or less. The trials indicate that bevacizumab in combination with 5-FU/FA, and bevacizumab in combination with IFL, is clinically effective in comparison to standard chemotherapy options for the first-line treatment of metastatic CRC. The health economic analysis suggests that the marginal cost-utility of bevacizumab plus IFL versus

A case of recurrent metastasis in the supraclavicular and axillary lymph nodes and vertebrae following irradiation and paclitaxel plus bevacizumab administration

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Nishiyama, Yasuyuki; Nishimura, Reiki; Ohsako, Tomofumi; Tashima, Rumiko; Nakano, Masahiro; Fujisue, Mamiko

2013-01-01

A 48-year-old woman with invasive ductal carcinoma of the left breast underwent breast-conserving surgery and axillary dissection; 19 months after surgery, she developed local recurrence. Subsequently, she underwent mastectomy and received endocrine therapy and chemotherapy. At 47 years of age, she developed pleural metastasis, which directly invaded the vertebrae as well as the right supraclavicular and right axillary lymph nodes. In addition, liver metastasis was observed. To avoid acute transverse myelopathy, the patient received radiation therapy to the vertebrae and the right supraclavicular and right axillary lymph nodes followed by paclitaxel plus bevacizumab administration. After 2 courses of paclitaxel plus bevacizumab, we observed a remarkable shrinkage of the vertebral tumor, and skin necrosis was observed in the right supraclavicular and right axillary region; in contrast, the liver metastasis had increased in size. After discontinuation of the combination therapy, the patient died of blood loss from the axillary skin defect. This wound healing complication might have arisen because of the synergistic effects of paclitaxel plus bevacizumab and irradiation. (author)

The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema.

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Al-Dhibi, Hassan; Hamade, Issam H; Al-Halafi, Ali; Barry, Maan; Chacra, Charbel Bou; Gupta, Vishali; Tabbara, Khalid F

2014-01-01

Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41 ± 16 years with a mean followup of 4 ± 1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8 ± 0.8 at baseline to 0.4 ± 0.5 at 1 month and 0.3 ± 0.5 at 3 months (P < 0.002, at 3 months). The mean macular thickness was 430 ± 132 μm at baseline. Following IVBI macular thickness improved to 286 ± 93 μm at 1 month and to 265 ± 88 μm at 3 months of followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

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Hassan Al-Dhibi

2014-01-01

Full Text Available Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months. The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months. Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

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Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

2015-01-01

Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

Acute anterior uveitis following intravitreal bevacizumab but not subsequent ranibizumab

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Antonopoulos C

2011-11-01

Full Text Available Christina Antonopoulos1, Maxwell Stem2, Grant M Comer21Department of Ophthalmology, Boston University, Boston, MA, USA; 2WK Kellogg Eye Center, Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USAPurpose: Previous reports have identified noninfectious uveitis as a potential sequela following both intravitreal bevacizumab and ranibizumab injections. We present two unique cases of acute anterior uveitis following intravitreal bevacizumab that did not occur with subsequent ranibizumab injections.Methods: Case report.Conclusion: These cases may reflect differences in the etiology of anterior uveitis following intravitreal bevacizumab and ranibizumab. Given these differences, it may be reasonable to offer ranibizumab to patients who have experienced presumed bevacizumab-induced anterior uveitis.Keywords: adverse effect, age-related macular degeneration, anterior uveitis, bevacizumab, ranibizumab, uveitis

Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

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Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eng, Cathy [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Maru, Dipen M. [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Clemons, Marilyn V. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-02-01

Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

A case report of long term bevacizumab treatment in multiresistant ovarian cancer

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Kargo, Anette Stolberg; Adimi, Parvin; Dahl-Steffensen, Karina

2016-01-01

Treatment of multiresistant ovarian cancer is palliative and patients have needs for less toxic treatment. Anti-angiogenic treatments have a less toxic profile, and bevacizumab has shown improvement of progression free survival (PFS) in front-line trials. Bevacizumab is generally introduced in co...... in combination with chemotherapy; however this case report will describe the use of single-agent bevacizumab for more than five years (102 cycles) in a patient with relapse of advanced ovarian cancer...

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

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Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

2011-01-01

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

International Nuclear Information System (INIS)

Finger, Paul T.

2008-01-01

Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

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Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

2011-03-01

The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

A recurrent ovarian cancer patient with a history of nine prior chemotherapy regimens who was safely treated with weekly paclitaxel plus bevacizumab and achieved a complete response: a case report

Directory of Open Access Journals (Sweden)

Takatori E

2015-08-01

Full Text Available Eriko Takatori,1 Tadahiro Shoji,1 Takayuki Nagasawa,1 Satoshi Takeuchi,1 Akira Hosoyachi,2 Toru Sugiyama1 1Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan; 2Department of Obstetrics and Gynecology, Iwate Prefectural Miyako Hospital, Miyako, Japan Abstract: Herein, we describe our experience with a recurrent ovarian cancer patient who was treated safely with bevacizumab and who achieved a complete response despite receiving nine prior chemotherapy regimens. The patient was a 54-year-old woman with stage IIIC recurrent ovarian serous adenocarcinoma (grade 3. Computed tomography (CT revealed that no evidence of ascites, multiple intraperitoneal dissemination, or intrapelvic lymph node metastases was present. The absence of bowel obstruction and disseminated lesions involving the intestinal tract was confirmed by CT. Performance status was 0, and a blood test also indicated preservation of major organ function. In our hospital, weekly paclitaxel plus bevacizumab therapy (paclitaxel at 80 mg/m2 on days 1, 8, and 15; bevacizumab at 15/mg/kg on day 1 and every 21 days thereafter was started. Eight cycles were administered, with no signs of gastrointestinal perforation, and the antitumor effect was evaluated as a complete response. The observed adverse events included grade 1 hyponatremia and grade 1 hypochloremia, and there was one grade 1 sensory peripheral neuropathy. These adverse events neither delayed treatment nor necessitated any dosage reductions. This case suggests that bevacizumab can be safely administered even to patients with recurrent ovarian cancer who have received three or more prior chemotherapy regimens if there are neither symptoms of bowel obstruction nor lesions suggestive of intestinal invasion on diagnostic imaging. Keywords: recurrent ovarian cancer, gastrointestinal perforation 

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

International Nuclear Information System (INIS)

Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert

2015-01-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m 2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [ 18 F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [ 61 Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

Energy Technology Data Exchange (ETDEWEB)

Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

2015-04-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2

Science.gov (United States)

Narayanan, Raja; Panchal, Bhavik; Stewart, Michael W; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Hasnat Ali, Mohd

2016-01-01

Purpose The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion. Patients and methods Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months. Results The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval −221.50 to −135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval −246.49 to −140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06). Conclusion Bimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it’s required more often in patients treated with bevacizumab. PMID:27330272

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity

Directory of Open Access Journals (Sweden)

Laskey RA

2014-03-01

Full Text Available Robin A Laskey,1 Scott D Richard,2 Ashlee L Smith,1 Jeff F Lin,1 Tiffany L Beck,3 Jamie L Lesnock,1 Joseph L Kelley 3rd,1 Alexander B Olawaiye,1 Paniti Sukumvanich,1 Thomas C Krivak4 1Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, 2Division of Gynecologic Oncology, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, 3Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of UPMC, Pittsburgh, 4Division of Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, PA, USA Purpose: Bevacizumab (Bev is associated with improved progression-free survival in advanced epithelial ovarian cancer. The use of Bev in patients with gynecologic malignancy is increasing; however, little is known about cumulative toxicity and response in patients retreated with Bev. Our goal was to determine cumulative side effects and response in patients retreated with Bev. Patients and methods: Women with recurrent gynecologic malignancy treated with Bev between January 2007 and March 2012 at a single institution were identified, including a subset who received Bev in a subsequent regimen. The primary outcome was Bev-associated toxicity, and the secondary outcome was response. Results: Of 83 patients that received Bev for recurrent disease, 23 were retreated with Bev and four received Bev maintenance. Three patients (13% developed grade 3 or 4 hypertension; all had a history of chronic hypertension. One (4.3% patient developed grade 3 proteinuria, and one (4.3% developed an enterovaginal fistula. Four patients discontinued Bev secondary to toxicity. Toxicity was not related to the cumulative number of cycles. Twenty-six percent of patients responded to Bev retreatment. On univariate analysis, there was a significant (P=0.003 overall survival advantage when the Bev-free interval was >9 months (95% confidence interval [CI] 4.9–43.7 compared to ≤9 months (95% CI 2.1–11.5, 24

Efficiency and safety of subconjunctival injection of anti-VEGF agent - bevacizumab - in treating dry eye.

Science.gov (United States)

Jiang, Xiaodan; Lv, Huibin; Qiu, Weiqiang; Liu, Ziyuan; Li, Xuemin; Wang, Wei

2015-01-01

Dry eye is a chronic inflammatory ocular surface disease with high prevalence. The current therapies for dry eye remain to be unspecific and notcomprehensive. This study aims to explore safety and efficacy of a novel treatment - subconjunctival injection of bevacizumab - in dry eye patients. Sixty-four eyes of 32 dry eye patients received subconjunctival injection of 100 μL 25 mg/mL bevacizumab. Dry eye symptoms, signs (corrected visual acuity, intraocular pressure, conjunctival vascularity, corneal staining, tear break-up time, Marx line score, and blood pressure), and conjunctival impression cytology were evaluated 3 days before and 1 week, 1 month, and 3 months after injection. Significant improvements were observed in dry eye symptoms, tear break-up time, and conjunctival vascularization area at all the visits after injection compared to the baseline (Pdry eye disease.

The effect of intravitreal bevacizumab and transpupillary thermotherapy on choroidal metastases and literature review

Directory of Open Access Journals (Sweden)

Chun-Ju Lin

2015-01-01

Full Text Available Aims : To represent the effects of transpupillary thermotherapy (TTT and intravitreal bevacizumab on choroidal metastases and review the literature. Settings and Design : A retrospective, interventional, noncomparative case series. Materials and Methods : A retrospective, interventional, noncomparative case series of five eyes in three patients with choroidal metastases was conducted. Fundus findings of choroidal metastases were divided into two types: Solitary or diffuse type. The size of the tumor was termed small (15 mm diameter. All eyes received one session of TTT followed by 3 weekly intravitreal bevacizumab injections as an adjuvant therapy. The parameters of treatment for TTT were 1.2-3 mm spot size, 150-300 mW, 60 s with the whole lesion covered confluently. The changes in preoperative and postoperative best-corrected visual acuity (BCVA were recorded. Serial color fundus photography and optical coherent tomography were performed to measure the treatment efficacy. Results : All eight choroidal metastases were solitary type. The size of six tumors was small, the size of one tumor was medium, and the size of one tumor was large. All five eyes of the three patients had improvement of BCVA after treatment. Fundus photos revealed tumor shrinkage and the mean shrinkage percentage was 61.27 ± 21.71%. Optical coherence tomography revealed complete resolution of serous retinal detachment. There was no recurrence after 6 months follow-up. Conclusions : TTT combined with intravitreal bevacizumab injections brought about beneficial effects in reducing tumor size and improving vision in all five eyes of the three patients. Despite the retrospective nature of our study, the absence of control group and the size limitation that, of course, limit the statistical power, TTT combined with intravitreal bevacizumab seems to be efficient in providing another cost-reducing and time-saving treatment option for patients with choroidal metastases. The

Acute sterile endophthalmitis following intravitreal bevacizumab: case series

Science.gov (United States)

Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

2014-01-01

Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

Directory of Open Access Journals (Sweden)

Jeevan Kumar

2012-01-01

Full Text Available We report a case of bevacizumab- (BEV- induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

Acute sterile endophthalmitis following intravitreal bevacizumab: case series

Directory of Open Access Journals (Sweden)

Orozco-Hernández A

2014-09-01

Full Text Available Axel Orozco-Hernández,1 Ximena Ortega-Larrocea,1 Gustavo Sánchez-Bermúdez,1 Gerardo García-Aguirre,1 Virgilio Morales Cantón,1 Raul Velez-Montoya2 1Retina Department, Asociación para Evitar la Ceguera en México IAP, Mexico City, Mexico; 2Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, Aurora, CO, USA Background: Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods: This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results: Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were

Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

DEFF Research Database (Denmark)

Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

2010-01-01

The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard tre...

Assessing Biological Response to Bevacizumab Using 18F-Fluoromisonidazole PET/MR Imaging in a Patient with Recurrent Anaplastic Astrocytoma

Directory of Open Access Journals (Sweden)

Ramon F. Barajas

2015-01-01

Full Text Available We present our initial experience in using single modality fluoromisonidazole (FMISO PET/MR imaging to noninvasively evaluate the biological effects induced by bevacizumab therapy in a patient treated for recurrent high grade glioma. In this index patient, bevacizumab therapy resulted in the development of nonenhancing tumor characterized by reduced diffusion and markedly decreased FMISO uptake in the setting of maintained CBF and CBV. These observations suggest that the dynamic biological interplay between tissue hypoxia and vascular normalization occurring within treated recurrent high grade glioma can be captured utilizing FMISO PET/MR imaging.

Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2.

Science.gov (United States)

Narayanan, Raja; Panchal, Bhavik; Stewart, Michael W; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Hasnat Ali, Mohd

2016-01-01

The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion. Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months. The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval -221.50 to -135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval -246.49 to -140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06). Bimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it's required more often in patients treated with bevacizumab.

Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial

DEFF Research Database (Denmark)

Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

2010-01-01

complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23-37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity......, for which 1 patient needed plastic surgery. One patient was excluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except...... for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone....

Comparison of structural outcome between intravitreal bevacizumab and laser treatment for type 1 retinopathy of prematurity after long-term follow-up

Institute of Scientific and Technical Information of China (English)

Yen-Yi Chen; Yun-Ju Chen; Yung-Ray Hsu; Fang-Ting Chen; Jia-Kang Wang

2016-01-01

Background:To compare the structural outcome of intravitreal bevacizumab (IVB) and laser treatment for type 1 retinopathy of prematurity (ROP). Methods: This is a retrospective comparative study. From December 2002 to April 2009, patients with type 1 ROP according to criteria of Early Treatment of Retinopathy of Prematurity (ETROP) study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern. From May 2009 to January 2015, we performed IVB for patients with type 1 ROP. The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group. The demographical data, postmenstrual age (PMA) for treatment, and fundus ifndings were recorded by chart review. The difference between laser and bevacizumab groups was compared by Studentt-test and Fisher exact test. Results: We collected 43 patients (86 eyes) with type 1 ROP, including 30 male and 13 female infants. Their mean gestation age and birth body weight (BBW) were 27.5 weeks and 1,034 gm. Zone I and zone II disease were found in 8 and 35 patients. The mean PMA for treatment was 37.3 weeks. The mean follow-up period was 54.4 months. Laser treatment was administered in 26 patients, and bevacizumab injection for 17 infants. Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization. Complete regression of ROP was found in 15 infants of bevacizumab group following the ifrst IVB. Four eyes in two patients (2/17, 11.7%) had recurrence of ROP and received additional injections and adjuvant laser treatment. There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management. Conclusions: Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes. Single session of laser ablation

(99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab.

Science.gov (United States)

Ma, Qingjie; Min, Kaiyin; Wang, Ting; Chen, Bin; Wen, Qiang; Wang, Fan; Ji, Tiefeng; Gao, Shi

2015-07-01

Functional imaging can help clinicians assess the individual response of advanced nonsquamous non-small cell lung cancer (NSCLC) to chemoradiation therapy plus bevacizumab. Our purpose is to investigate the ability of (99m)Tc-3PRGD2 single photon emission computed tomography/computed tomography (SPECT/CT) in predicting the early response to treatment. Patients with advanced nonsquamous NSCLC diagnosed by histological or cytological examination were imaged with (99m)Tc-3PRGD2 SPECT/CT at 3 time points: 1-3 days before the start of treatment (SPECT1), 40 Gy radiotherapy with 2 cycles of chemotherapy plus bevacizumab (SPECT2) and 4 weeks after chemoradiotherapy plus bevacizumab (SPECT3). The images were evaluated semiquantitatively by measuring the tumor to non-tumor ratio (T/N) and calculating the percentage change in T/N ratio. Short-term outcome was assessed by the treatment response evaluation according to the Response Evaluation Criteria in Solid Tumors criteria as: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were divided two groups: responders (CR and PR) and nonresponders (SD and PD). To determine a threshold for percent reduction in T/N ratios, receiver-operating characteristic (ROC) curve analysis was used. Patients were grouped again based on the threshold of P1 (the change percentage from SPECT1 to SPECT2) and P2 (the change percentage from SPECT1 to SPECT3): P1 responders and P1 nonresponders; P2 responders and P2 nonresponders. Patients were followed up starting 4 weeks after completion of therapy and then every 3 months for the first 2 years and every 6 months after 2 years. OS of P1 responders, P1 nonresponders, P2 responders and P2 nonresponders was estimated and graphically illustrated using the Kaplan-Meier method and the log-rank test was used to test the null hypotheses of equal OS in subgroups of patients. A total of 28 patients completed all imaging and treatment. All primary

Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

Science.gov (United States)

Stokes, P; Rimmer, J

2018-03-01

Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT. A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life. A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis. Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments. The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

International Nuclear Information System (INIS)

Finger, Paul T.; Chin, Kimberly J.

2012-01-01

Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6–8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

2012-02-01

Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study

Energy Technology Data Exchange (ETDEWEB)

Bostroem, J.P. [University of Bonn Medical Center, Department of Neurosurgery, Bonn (Germany); MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); Seifert, M.; Greschus, S. [University of Bonn Medical Center, Department of Radiology, Bonn (Germany); Schaefer, N.; Herrlinger, U. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); Glas, M. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); University of Bonn Medical Center, Stem Cell Pathologies, Institute of Reconstructive Neurobiology, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Lammering, G. [MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Heinrich-Heine-University of Duesseldorf, Department of Radiotherapy and Radiation Oncology, Duesseldorf (Germany)

2014-04-15

Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma. (orig.) [German] In zwei aktuellen retrospektiven Kohortenstudien konnte eine Wirksamkeit von Bevacizumab bei Patienten mit rezidivierenden atypischen und

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

International Nuclear Information System (INIS)

Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

2012-01-01

Background: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Materials and methods: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6–65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan–Meier survival curves (log-rank test). Results: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. Discussion and conclusion: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

Science.gov (United States)

Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

2012-10-01

The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

DEFF Research Database (Denmark)

Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

2014-01-01

in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results...... treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor...... growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations...

An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

Science.gov (United States)

DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

2015-05-01

Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

Circulating Tumor Cell Count Is a Prognostic Factor in Metastatic Colorectal Cancer Patients Receiving First-Line Chemotherapy Plus Bevacizumab: A Spanish Cooperative Group for the Treatment of Digestive Tumors Study

Science.gov (United States)

Maestro, M. Luisa; Gómez-España, Auxiliadora; Rivera, Fernando; Valladares, Manuel; Massuti, Bartomeu; Benavides, Manuel; Gallén, Manuel; Marcuello, Eugenio; Abad, Albert; Arrivi, Antonio; Fernández-Martos, Carlos; González, Encarnación; Tabernero, Josep M.; Vidaurreta, Marta; Aranda, Enrique; Díaz-Rubio, Eduardo

2012-01-01

Background. The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. Patients and Methods. One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. Results. The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095). Conclusions. The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients. PMID:22643538

Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

Science.gov (United States)

Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

2018-01-01

Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

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Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

2017-01-01

Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

Science.gov (United States)

Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

2017-05-20

Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

Timing of Administration of Bevacizumab Chemotherapy Affects Wound Healing Following Chest Wall Port Placement

OpenAIRE

Erinjeri, Joseph P; Fong, Abigail J; Kemeny, Nancy E; Brown, Karen T; Getrajdman, George I; Solomon, Stephen B

2010-01-01

The risk of a wound dehiscence requiring chest wall port explant in patients treated with bevacizumab is inversely proportional to the interval between bevacizumab administration and port placement. There is significantly higher risk of wound dehiscence when the interval between bevacizumab administration and chest wall port placement is less than 14 days.

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

DEFF Research Database (Denmark)

Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

2008-01-01

Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled...... was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow-up examinations (P Macular thickness improved significantly at all time...

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

Science.gov (United States)

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

Science.gov (United States)

Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

2012-06-01

The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Targeting Src family kinases inhibits bevacizumab-induced glioma cell invasion.

Directory of Open Access Journals (Sweden)

Deborah Huveldt

Full Text Available Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM. Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab's influence on glioma biology and block it's actions towards cell invasion. To explore the mechanism(s of GBM cell invasion we have examined a panel of serially transplanted human GBM lines grown either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1 activation of Src family kinases (SFKs is common in GBM, 2 the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3 SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support testing the combination of dasatinib with bevacizumab in the clinic.

Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer

Directory of Open Access Journals (Sweden)

Alberto Montero

2012-12-01

Full Text Available This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2. In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m2, nab-paclitaxel 150 mg/m2, and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triple-negative metastatic breast cancer.

Discontinuous Schedule of Bevacizumab in Colorectal Cancer Induces Accelerated Tumor Growth and Phenotypic Changes

Directory of Open Access Journals (Sweden)

Selma Becherirat

2018-04-01

Full Text Available Antiangiogenics administration in colorectal cancer patients seemed promising therapeutic approach. Inspite of early encouraging results, it however gave only modest clinical benefits. When AAG was administered with discontinuous schedule, the disease showed acceleration in certain cases. Though resistance to AAG has been extensively studied, it is not documented for discontinuous schedules. To simulate clinical situations, we subjected a patient-derived CRC subcutaneous xenograft in mice to three different protocols: 1 AAG (bevacizumab treatment for 30 days (group A (group B was the control, 2 bevacizumab treatment for 50 days (group C and bevacizumab for 30 days and 20 without treatment (group D, and 3 bevacizumab treatment for 70 days (group E and 70 days treatment with a drug-break period between day 30 and 50 (group F. The tumor growth was monitored, and at sacrifice, the vascularity of tumors was measured and the proangiogenic factors quantified. Tumor phenotype was studied by quantifying cancer stem cells. Interrupting bevacizumab during treatment accelerated tumor growth and revascularization. A significant increase of proangiogenic factors was observed when therapy was stopped. On withdrawal of bevacizumab, as also after the drug-break period, the plasmatic VEGF increased significantly. Similarly, a notable increase of CSCs after the withdrawal and drug-break period of bevacizumab was observed (P<.01. The present study indicates that bevacizumab treatment needs to be maintained because discontinuous schedules tend to trigger tumor regrowth, and increase tumor resistance and CSC heterogeneity.

Wound healing complications in brain tumor patients on Bevacizumab.

Science.gov (United States)

Ladha, Harshad; Pawar, Tushar; Gilbert, Mark R; Mandel, Jacob; O-Brien, Barbara; Conrad, Charles; Fields, Margaret; Hanna, Teresa; Loch, Carolyn; Armstrong, Terri S

2015-09-01

Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

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Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

2017-09-01

Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

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Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily

Bevacizumab in Treatment of High-Risk Ovarian Cancer—A Cost-Effectiveness Analysis

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Herzog, Thomas J.; Hu, Lilian; Monk, Bradley J.; Kiet, Tuyen; Blansit, Kevin; Kapp, Daniel S.; Yu, Xinhua

2014-01-01

Objective. The objective of this study was to evaluate a cost-effectiveness strategy of bevacizumab in a subset of high-risk advanced ovarian cancer patients with survival benefit. Methods. A subset analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high-risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost-effectiveness ratio per life-year saved was established. Results. The estimated cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high-risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of B was $167,771 per life-year saved. Conclusion. In this clinically relevant subset of women with high-risk advanced ovarian cancer with overall survival benefit after bevacizumab, our economic model suggests that the incremental cost of bevacizumab was approximately $170,000. PMID:24721817

Effect of Intra Vitreal Injection of Bevacizumab on Intra-Occular Pressure

International Nuclear Information System (INIS)

Jaffar, S.; Tayyab, A.; Matin, Z. I.; Masrur, A.; Naqaish, R.

2016-01-01

Background: Bevacizumab has been in use as a therapeutic agent for macular oedema for several years. While its efficacy has been well documented, its use has been shown to cause a transient rise in the intra-ocular pressure. The aim of this study was to evaluate the long term effect of intra-vitreal injection of Bevacizumab on Intra-ocular pressure. Methods: One hundred eyes (n=100) of one hundred patients, requiring intra-vitreal injection of Bevacizumab for diabetic macular oedema were recruited from Shifa Foundation Community Health Centre (SFCHC) between January and December 2014. Patients of glaucoma, ocular hyper-tension, known allergy to Bevacizumab or had injections of Bevacizumab prior to the study were excluded. Intra-ocular pressure was measured using a Goldmann applanation tonometer, prior to, and at six and twelve months after the injection. The pre- and post- injection Intra-ocular pressure was entered into the database. Test of significance was applied to investigate whether there was a significant change in intra-ocular pressure after the injection. Results: The mean age of the patient was 56.97 years (±14.97). The mean intra-ocular pressure was 13.86 (±3.16) mmHg before injection, while post-injection mean Intra-Ocular pressure was 14.21 (±3.12) mmHg and 13.79 (±3.07) at six and twelve months respectively. Between baseline and six months there was a statistically significant difference in intra-ocular pressure (p=0.03), while no significant difference existed in the intra-ocular pressure between baseline and twelve months (p=0.92). Conclusion: Intra-vitreal injection of Bevacizumab is associated with a statically significant rise in intra-ocular pressure at six months, while no significant difference was seen at twelve months compared to baseline. (author)

MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

DEFF Research Database (Denmark)

Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

2015-01-01

Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM). However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy. Recent findings from a randomized phase-3 study (AVAglio) indicate that patients...... with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study...... was to evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...

Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.

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Bear, Harry D; Tang, Gong; Rastogi, Priya; Geyer, Charles E; Liu, Qing; Robidoux, André; Baez-Diaz, Luis; Brufsky, Adam M; Mehta, Rita S; Fehrenbacher, Louis; Young, James A; Senecal, Francis M; Gaur, Rakesh; Margolese, Richard G; Adams, Paul T; Gross, Howard M; Costantino, Joseph P; Paik, Soonmyung; Swain, Sandra M; Mamounas, Eleftherios P; Wolmark, Norman

2015-09-01

NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and

Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

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Ayse Oner

2018-04-01

Full Text Available AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer.

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Montero, Alberto J; Avancha, Kiran; Glück, Stefan; Lopes, Gilberto

2012-04-01

Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

International Nuclear Information System (INIS)

Velenik, Vaneja; Omejc, Mirko; Ocvirk, Janja; Music, Maja; Bracko, Matej; Anderluh, Franc; Oblak, Irena; Edhemovic, Ibrahim; Brecelj, Erik; Kropivnik, Mateja

2011-01-01

Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m 2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower

Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7)

DEFF Research Database (Denmark)

Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus

2015-01-01

BACKGROUND: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results...... of the trial. METHODS: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation....... This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. FINDINGS: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end...

Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

Science.gov (United States)

Herbst, Roy S; Redman, Mary W; Kim, Edward S; Semrad, Thomas J; Bazhenova, Lyudmila; Masters, Gregory; Oettel, Kurt; Guaglianone, Perry; Reynolds, Christopher; Karnad, Anand; Arnold, Susanne M; Varella-Garcia, Marileila; Moon, James; Mack, Philip C; Blanke, Charles D; Hirsch, Fred R; Kelly, Karen; Gandara, David R

2018-01-01

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive. We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2 ; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m 2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712). Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control

A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

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Affronti ML

2016-12-01

Full Text Available Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG remains poor, improving quality of life (QoL through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55% CINV complete response (CR; no emesis or use of rescue antiemetic with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg and dexamethasone (DEX; 10 mg received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy. Secondary end points included delayed CINV CR (days 2–5, overall CINV CR (days 1–5, and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome

Biochemical liver function test parameter levels in relation to treatment response in liver metastatic colorectal patients treated with FOLFOX4 with or without bevacizumab

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Denić Kristina

2016-01-01

Full Text Available Introduction. Combined use of bevacizumab and conventional anticancer drugs leads to a significant improvement of treatment response in patients with metastatic colorectal carcinoma (CRC. Conventional treatment protocols exert undesired effects on the liver tissue. Hepatotoxic effects are manifested as a disturbance of liver function test parameters. The relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Objective. The objective of our study was to examine whether clinical outcome in patients with liver metastatic CRC correlates with the level of liver function test parameters. Methods. The study included 96 patients with untreated liver metastatic CRC who received FOLFOX4 protocol with or without bevacizumab. Biochemical liver parameters were performed before and after the treatment completion. Treatment response was evaluated as disease regression, stable disease, and disease progression. The patients were divided into three groups according to the accomplished treatment response. Results. In the group of patients with disease regression the post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and bilirubin were statistically significantly increased. In contrast to this, gamma-glutamyltransferase and protein post-treatment values were significantly lower in relation to initial values. In patients with stable disease, difference was found only in the level of proteins being lower after the treatment. In patients with disease progression, values of aspartate aminotransferase and bilirubin were significantly increased after completed treatment. Conclusion. Treatment responses are not completely associated with the level of liver function test parameters. The only parameter which correlated with treatment response is gamma-glutamyltransferase. Its decrease is accompanied with disease regression.

Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial)--a phase II non-randomised trial.

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Mitry, Emmanuel; Walter, Thomas; Baudin, Eric; Kurtz, Jean-Emmanuel; Ruszniewski, Philippe; Dominguez-Tinajero, Sophie; Bengrine-Lefevre, Leïla; Cadiot, Guillaume; Dromain, Clarisse; Farace, Françoise; Rougier, Philippe; Ducreux, Michel

2014-12-01

Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical study on bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer

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Li-Ping Yang1

2017-06-01

Full Text Available Objective: To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules. Methods: A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined. Results: 3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group. Conclusion: Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

Science.gov (United States)

West, Howard L; Moon, James; Wozniak, Antoinette J; Mack, Philip; Hirsch, Fred R; Bury, Martin J; Kwong, Myron; Nguyen, Dorothy D; Moore, Dennis F; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R

2018-01-01

Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

International Nuclear Information System (INIS)

Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner; Staberg, Mikkel; Villingshøj, Mette; Lassen, Ulrik

2014-01-01

Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed

Sigmoid-vaginal fistula during bevacizumab treatment diagnosed by fistulography.

Science.gov (United States)

Hayashi, C; Takada, S; Kasuga, A; Shinya, K; Watanabe, M; Kano, H; Takayama, T

2016-12-01

There have been several reports describing rectovaginal fistula development after bevacizumab treatment, and these fistulas were diagnosed by CT scan or colonoscopy. We report a case of sigmoid-vaginal fistula diagnosed by fistulography. The case is a 53-year-old woman who was treated for chronic myelogenous leukaemia and gynaecological cancers 8 years previously. At 52 years of age, she was diagnosed with colon cancer and had a partial colectomy performed. One year after surgery, colon cancer recurred, and she was treated with anticancer agents, including bevacizumab. During chemotherapy, she complained of a foul smelling discharge from the vagina. Fistulography revealed a sigmoid-vaginal fistula. This is the first report of vaginal fistulography performed on a patient who was treated with bevacizumab. Fistulography may be useful for detecting sigmoid-vaginal fistula. © 2016 John Wiley & Sons Ltd.

An overview of fotemustine in high-grade gliomas: from single agent to association with bevacizumab.

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Lombardi, Giuseppe; Farina, Patrizia; Della Puppa, Alessandro; Cecchin, Diego; Pambuku, Ardi; Bellu, Luisa; Zagonel, Vittorina

2014-01-01

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

Science.gov (United States)

Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

2012-02-01

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials.

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Cremolini, Chiara; Milione, Massimo; Marmorino, Federica; Morano, Federica; Zucchelli, Gemma; Mennitto, Alessia; Prisciandaro, Michele; Lonardi, Sara; Pellegrinelli, Alessio; Rossini, Daniele; Bergamo, Francesca; Aprile, Giuseppe; Urbani, Lucio; Morelli, Luca; Schirripa, Marta; Cardellino, Giovanni Gerardo; Fassan, Matteo; Fontanini, Gabriella; de Braud, Filippo; Mazzaferro, Vincenzo; Falcone, Alfredo; Pietrantonio, Filippo

2018-04-01

Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than

The Predictive Value of Early In-Treatment 18F-FDG PET/CT Response to Chemotherapy in Combination with Bevacizumab in Advanced Nonsquamous Non-Small Cell Lung Cancer.

Science.gov (United States)

Usmanij, Edwin A; Natroshvili, Tinatin; Timmer-Bonte, Johanna N H; Oyen, Wim J G; van der Drift, Miep A; Bussink, Johan; Geus-Oei, Lioe-Fee de

2017-08-01

18 F-FDG PET/CT is potentially applicable to predict response to chemotherapy in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Methods: In 25 patients with advanced nonsquamous NSCLC, 18 F-FDG PET/CT was performed before treatment and after 2 wk, at the end of the second week of first cycle carboplatin-paclitaxel and bevacizumab (CPB) treatment. Patients received up to a total of 4 cycles of CPB treatment. Maintenance treatment with bevacizumab monotherapy was continued until progressive disease without significant treatment-related toxicities of first-line treatment. In the case of progressive disease, bevacizumab was combined with erlotinib. SUV corrected for lean body mass (SUL and SUL peak ) were obtained. PERCIST were used for response evaluation. These semiquantitative parameters were correlated with progression-free survival and overall survival (OS). Results: Metabolic response, defined by a significant reduction in SUL peak of 30% or more after 2 wk of CPB, was predictive of progression-free survival and OS. For partial metabolic responders ( n = 19), the median OS was 22.8 mo. One-year and 2-y OS were 79% and 47%, respectively. Nonmetabolic responders ( n = 6) (stable metabolic disease or progressive disease) showed a median OS of 4.4 mo (1-y and 2-y OS was 33% and 0%, respectively) ( P predictive of outcome to first-line chemotherapy with bevacizumab in patients with advanced nonsquamous NSCLC. This enables identification of patients at risk of treatment failure, permitting treatment alternatives such as early switch to a different therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2

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Narayanan R

2016-06-01

Full Text Available Raja Narayanan,1 Bhavik Panchal,1 Michael W Stewart,2 Taraprasad Das,1 Jay Chhablani,1 Subhadra Jalali,1 Mohd Hasnat Ali3 On behalf of MARVEL study group 1Smt. Kanuri Santhamma Centre for Vitreo Retinal Diseases, L V Prasad Eye Institute, Hyderabad, India; 2Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USA; 3Department of Biostatistics, L V Prasad Eye Institute, Hyderabad, India Purpose: The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion.Patients and methods: Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT; during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months.Results: The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. ­Moreover, 55/75 (73.33% participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 µm (P<0.001; 95% ­confidence interval -221.50 to -135.0 in the ranibizumab group and 184.78 µm (P<0.001; 95% confidence interval -246.49 to -140.0 in the bevacizumab group (P=0.079. More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06.Conclusion: Bimonthly evaluations after month 6

5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

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Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

2015-01-01

Background Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. Conclusion While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer. PMID:26109878

5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

International Nuclear Information System (INIS)

Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

2015-01-01

Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer

Optimizing bevacizumab dosing in glioblastoma: less is more.

Science.gov (United States)

Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

2017-10-01

Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

OpenAIRE

Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas; Hatschek, Thomas

2017-01-01

Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advance...

Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

DEFF Research Database (Denmark)

Steffensen, Karina Dahl; Madsen, Christine Vestergaard; Andersen, Rikke Fredslund

2014-01-01

of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance......-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.......AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment...

Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

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Zheng-Jun Hu

2015-05-01

Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3～5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34～38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

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Giuseppe Lombardi

2014-01-01

Full Text Available Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

The Effect of Intravitreal Bevacizumab on Apoptosis of Rat Retina Cells

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Özcan Kayıkçıoğlu

2013-01-01

Full Text Available Pur po se: To investigate the apoptotic effects of intravitreal bevacizumab on rat retinal cells. Ma te ri al and Met hod: Thirty-six male adult Swiss albino rats were randomly divided into two groups. The first group was applied 0.25 mg bevacizumab in 0.01 ml saline, and the second group received the same amount of saline intravitreally. Each group was divided into 3 subgroups. The animals were sacrificed and their globes were enucleated at the 3rd, 24th, and 72nd hours of the experiment. Enucleated eyes were preserved for histological analysis, immunohistochemical analysis of caspase-3, caspase-8, caspase-9, Fas/Fas L, VEGF and VEGF receptors (Flt-1, Flk-1, and TUNEL staining. Re sults: Histological evaluation showed no sign of retinal toxicity in both groups. In TUNEL staining, TUNEL(+ cells were detected in all subgroups, but the number of positive cells was relatively lower in bevacizumab treatment group that reached statistically significant level at 24 and 72 hours of treatment (p<0.001. Immunohistochemical analysis revealed that in saline-treated subgroups, immunoreactivity was more pronounced for all apoptosis-inducing proteins compared to bevacizumab-treated group. Also immunoreactivity of VEGF was prominent in saline treated group. For VEGF receptors, staining was only positive for Flt-1 at the 3rd hour in the control group. Dis cus si on: Bevacizumab did not have apoptosis-inducing potential compared to saline solution in short term, which was documented with TUNEL and immunohistochemical staining. (Turk J Ophthalmol 2013; 43: 39-44

A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy.

Science.gov (United States)

Weiss, Jared M; Villaruz, Liza C; Socinski, Mark A; Ivanova, Anastasia; Grilley-Olson, Juneko; Dhruva, Nirav; Stinchcombe, Thomas E

2014-11-01

Platinum-based chemotherapy with bevacizumab is a standard therapy for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with non-squamous (NS) histology. Mechanisms of resistance to bevacizumab include increased VEGF signaling or activation of VEGF receptors. Pazopanib is a multi-targeted VEGF receptor tyrosine kinase with single agent activity in NSCLC. Stage IIIB/IV patients with adequate organ function, who progressed on a bevacizumab containing therapy were eligible if it had been ≤8 weeks since the last bevacizumab treatment. The primary end-point was disease control rate (DCR), defined as partial or complete response, or stable disease for ≥12 weeks. Patients were assessed radiographically every 2 cycles (6 weeks). A Simon 2-stage design was used, and if in the first stage ≤4 of 17 patients experienced disease control the trial was to have been stopped for futility. An unplanned analysis was performed after 15 patients were evaluable secondary to slow accrual. Between December 2010 and November 2013, 15 patients were treated on trial. The median age was 61 years (range 39-74), and all patients had stage IV disease. Of the 15 patients, 4 discontinued therapy prior to cycle 2 evaluation due to adverse events (n=3) and medical illness (n=1), 5 patients had progressive disease, 4 patients had stable disease for <12 weeks, and 2 patients had stable disease for ≥12 weeks. No responses were observed. The DCR observed was 13% (2/15), and the trial did not meet the criteria to proceed to the second stage. Episodes of grade 3 treatment related toxicities observed included: increased ALT (n=2), increased AST (n=1), anorexia (n=3), fatigue (n=3), hypertension (n=1), infection (n=1), mucositis (n=2), nausea (n=3), pericardial effusion (n=1), and vomiting (n=1). Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan

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Urup, Thomas; Dahlrot, Rikke Hedegaard; Grunnet, Kirsten

2016-01-01

Background Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan....... Material and methods A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population. Prognostic models were generated by means of multivariate logistic and Cox regression analysis. Results In multivariate...

Increased genitourinary fistula rate after bevacizumab in recurrent cervical cancer patients initially treated with definitive radiochemotherapy and image-guided adaptive brachytherapy

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Sturdza, Alina; Kirisits, Christian; Poetter, Richard [Medical University of Vienna, Department of Radiation Oncology, Comprehensive Cancer CenterVienna, Vienna (Austria); Hofmann, Sandra; Kranawetter, Marlene; Grimm, Christoph; Schwameis, Richard [Medical University Vienna, Department of general Gynecology and Gynecologic Oncology, Comprehensive Cancer Center Vienna, Vienna (Austria); Polterauer, Stephan; Reinthaller, Alexander [Medical University Vienna, Department of general Gynecology and Gynecologic Oncology, Comprehensive Cancer Center Vienna, Vienna (Austria); Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology, Vienna (Austria); Krainer, Michael [Medical University Vienna, Clinical Division of Oncology, Department of Medicine 1, Comprehensive Cancer Center, Vienna (Austria)

2017-12-15

Patients with recurrent cervical cancer (RecCC) who received definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT) as primary treatment are currently treated in our institution with palliative intent by chemotherapy (CHT) combined with bevacizumab (BEV). We aim to evaluate the risk of gastrointestinal (GI)/genitourinary (GU) fistula formation in these patients. Data of 35 consecutive patients with RecCC treated initially with radiochemotherapy and IGABT were collected. Known and presumed risk factors associated with fistula formation were evaluated. Fistula rate was compared between patients receiving CHT or CHT+BEV. Of the 35 patients, 25 received CHT and 10 patients received CHT+BEV. Clinical characteristics were comparable. Fistulae were reported in 6 patients: two fistulae (8%) in the CHT group, four (40%) in the CHT+BEV group. GU fistula occurred in the CHT+BEV group only (3/4). Of these 6 patients with fistulae, 5 (83%) had undergone previous invasive procedures after the diagnosis of RecCC and 1 patient had undergone pelvic re-irradiation; 3/6 patients had developed a local recurrence. No other risk factors for fistula formation were identified. In patients with RecCC after definitive radiochemotherapy including IGABT, the addition of BEV to CHT may increase the risk for GU fistula formation, particularly after invasive pelvic procedures. Future clinical studies are required to identify predictors for fistula formation to subsequently improve patient selection for the addition of BEV in the RecCC setting. (orig.) [German] Patientinnen mit Rezidiv eines Zervixkarzinoms (RecCC), die primaer eine bildgesteuerte adaptive Brachytherapie (IGABT) und kombinierte Radiochemotherapie (RCHT) erhalten hatten, werden derzeit in unserem Institut mit einer Kombination aus Chemotherapie (CHT) und Bevacizumab (BEV) behandelt. Ziel dieser Studie war es, das Risiko fuer das Auftreten gastrointestinaler (GI) sowie urogenitaler (GU) Fisteln unter CHT

A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

Science.gov (United States)

Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

2017-10-01

This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

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Artzi, Moran, E-mail: artzimy@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Bokstein, Felix, E-mail: felixb@tlvmc.gov.il [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Blumenthal, Deborah T., E-mail: deborahblumenthal@gmail.com [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Aizenstein, Orna, E-mail: Ornaaizenstein@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Liberman, Gilad, E-mail: giladliberman@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan (Israel); Corn, Benjamin W., E-mail: bencorn@tlvmc.gov.il [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Institute of Radiotherapy, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Sagol School of Neuroscience, Tel Aviv University, Tel Aviv (Israel)

2014-07-15

Background: Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T{sub 2}-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. Methods and materials: Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10 mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. Results: The non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T{sub 1}-weighted (58 ± 10%) and hyperintense FLAIR (53 ± 9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r = −0.86, p = 0.003, week 16: r = −0.99, p = 0.001). Conclusion: Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

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Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

2015-01-01

Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer

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Hansen, T F; Carlsen, A L; Heegaard, N H H

2015-01-01

BACKGROUND: This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab.METHODS: The study included 68 patients. Blood samples (plasma) were collected b...

Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases

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Rose Isono-Nakata

2018-05-01

Full Text Available Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV. One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

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Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

2012-01-01

The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

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Guthoff, Rainer; Guthoff, Tanja; Meigen, Thomas; Goebel, Winfried

2011-01-01

To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study

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Lubner, Sam J.; Mahoney, Michelle R.; Kolesar, Jill L.; LoConte, Noelle K.; Kim, George P.; Pitot, Henry C.; Philip, Philip A.; Picus, Joel; Yong, Wei-Peng; Horvath, Lisa; Van Hazel, Guy; Erlichman, Charles E.; Holen, Kyle D.

2010-01-01

Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer. PMID:20530271

Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

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Ayumu Matsuoka

Full Text Available Bevacizumab (BEV, a humanized anti-vascular endothelial growth factor (VEGF monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83 were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095; at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016. At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017. In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012.The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast

A randomised, double-masked, controlled study of the efficacy and safety of intravitreal bevacizumab versus ranibizumab in the treatment of macular oedema due to branch retinal vein occlusion: MARVEL Report No. 1.

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Narayanan, Raja; Panchal, Bhavik; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Ali, M Hasnat

2015-07-01

To assess the efficacy and safety of intravitreal bevacizumab (IVB) compared with ranibizumab (IVR) in the treatment of macular oedema due to branch retinal vein occlusion (BRVO). In this prospective, randomised, non-inferiority trial, 75 participants with macular oedema due to BRVO received intravitreal injections of ranibizumab or bevacizumab after 1:1 block randomisation. The primary outcome measure was the difference in mean changes in best-corrected visual acuity (BCVA) at 6 months. Secondary outcome measures included mean change in central retinal thickness (CRT), the proportion of patients improving by >15 letters and the proportion of patients developing neovascularisation. Participants received either IVR (n=37) or IVB (n=38). The mean BCVA at baseline was 52.8±14.4 letters (20/80) and 56.1±10.0 letters (20/80) (p=0.24) in the ranibizumab and bevacizumab groups, respectively. At 6 months, the mean gains in BCVA were +18.1 letters (p<0.0001; 95% CI, +12.8 to +22.6) in the ranibizumab group and +15.6 letters (p<0.0001; 95% CI +12.0 to +20.5) in the bevacizumab group. The difference between the mean visual gains of the treated groups (bevacizumab-ranibizumab) was -2.5 letters (95% CI -8.0 to +5.0; p=0.74). Mean reductions in CRT at 6 months were 177.1±122.3 µm in the ranibizumab group (p<0.0001) and 201.7±166.2 µm in the bevacizumab group (p<0.0001), with no significant difference between the two groups (p=0.48). The mean numbers of ranibizumab and bevacizumab injections were 3.2±1.5 and 3.0±1.4, respectively (p=0.55). Two serious adverse events occurred in the ranibizumab group and one in the bevacizumab group but both were unrelated to intravitreal injections. This study demonstrated significant gain in visual acuity in eyes with BRVO treated with either bevacizumab or ranibizumab. Pro-re-nata strategy was effective in maintaining the visual gain. http://www.ctri.nic.in/ CTRI/2012/01/003120. Published by the BMJ Publishing Group Limited

Effects of topical bevacizumab application on early bleb failure after trabeculectomy: observational case series

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Klos-Rola J

2013-09-01

Full Text Available Justyna Klos-Rola, Maria Tulidowicz-Bielak, Tomasz Zarnowski Department of Ophthalmology, Medical University of Lublin, Lublin, Poland Background: The aim of this study was to evaluate the influence of topical bevacizumab on the formation and function of filtering blebs in eyes with early bleb failure after antiglaucoma surgery. Methods: Of all patients who underwent mitomycin-augmented trabeculectomy for glaucoma in the Department of Ophthalmology at the Medical University in Lublin, Poland, between March 2009 and March 2010, a total of 21 eyes from 20 patients with injected filtration bleb 9.8 ± 4.7 days after surgery were included in this observational case series. All patients were treated with standard steroid therapy and topical bevacizumab 5 mg/mL five times a day for 20.9 ± 9.8 days. Patients were followed up every other day, and a full eye examination was performed 14, 30, 60, and 180 days after initiation of treatment. Blebs were evaluated for vascularity by slit-lamp examination with concomitant photographic documentation and intraocular pressure measurement. Results: Elevated functional bleb with significantly reduced vascularity was present in 16 eyes, and was flat and nonfunctional in five eyes. Intraocular pressure in all eyes decreased from a mean of 26.6 ± 9.6 mmHg before surgery to 14.6 ± 7.7 mmHg and 15.8 ± 8.3 mmHg at 2 and 6 months after surgery, respectively. Filtration bleb leak was noted in three eyes while on treatment with bevacizumab. Conclusion: Topical application of bevacizumab might favor functional bleb formation after trabeculectomy in eyes with a high risk of failure. Keywords: glaucoma, trabeculectomy, bleb failure, bevacizumab

Intravitreal bevacizumab in pigmented rabbit eyes: histological analysis 90 days after injection Bevacizumabe intravítreo em olhos de coelhos não albinos: análise histológica 90 dias após a injeção

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João Carlos Diniz Arraes

2009-10-01

Full Text Available PURPOSE: To evaluate bevacizumab toxicity in neurosensorial retina and retinal pigment epithelium in pigmented rabbit eyes by means of histological studies. METHODS: Thirty eyes of fifteen rabbits were distributed into three groups: sham group (S, that received a 0.1 ml balanced saline solution (BSS intravitreal injection (10 eyes; group 1, that received a 1.25 mg (0.1 ml bevacizumab intravitreal injection (10 eyes; and group 2, that received a 2.5 mg (0.1 ml bevacizumab intravitreal injection (10 eyes. Rabbits were sacrificed 90 days after the procedure and both eyes of each rabbit were enucleated. A histological examination of neurosensorial retina and retinal pigmented epithelium (RPE was performed. Its morphological features and layer thickness were also analyzed. RESULTS: No histological differences in neurosensorial retina or in retinal pigmented epithelium were found and layer thickness did not differ significantly between balanced saline solution-injected eyes and bevacizumab-injected eyes. CONCLUSION: After a 90-day follow-up period, a single 1.25 or 2.5 mg bevacizumab intravitreal injection did not lead to toxic damage in the neurosensorial retina and retinal pigment epithelium of pigmented rabbit eyes, and it appears to be a safe procedure for retinal neovascular diseases.OBJETIVOS: Avaliar a toxicidade do bevacizumabe na retina neurossensorial e epitélio pigmentado da retina (EPR em olhos de coelhos não albinos pelos estudos histológicos. MÉTODOS: Trinta olhos de 15 coelhos foram distribuídos em três grupos: 10 olhos no grupo placebo (P, que recebeu uma injeção intravítrea de 0,1 ml de solução salina balanceada (SSB; 10 olhos no grupo 1, que recebeu uma injeção intravítrea de 1,25 mg (0,1 ml de bevacizumabe; e 10 olhos no grupo 2, que recebeu uma injeção intravítrea de 2,5 mg (0,1 ml de bevacizumabe. Os coelhos tiveram seus dois olhos enucleados sob anestesia geral e submetidos à eutanásia 90 dias após a inje

Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

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Ökkeş Baz

2017-06-01

Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

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Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

2011-01-01

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis

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Ruan GY

2018-01-01

Full Text Available Guanyu Ruan,1,* Lixiang Ye,2,* Guifen Liu,3 Jian An,3 Jalid Sehouli,4 Pengming Sun1,3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, 2Fujian Center for Safety Evaluation of New Drugs, Fujian Medical University, 3Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Gynecologic Oncology and Gynecology, Charité Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer, University of Berlin, Berlin, Germany *These authors contributed equally to this work Abstract: The impact of bevacizumab (an anti-vascular endothelial growth factor therapy remains uncertain, which has been the focus of studies on the management of epithelial ovarian cancer (EOC. To investigate the efficacy of bevacizumab combinations with different regimens in the treatment of patients with EOC, a meta-analysis of Phase III randomized controlled trials was conducted. The databases searched included PubMed, Embase, ClinicalTrials.gov, Chinese Knowledge Infrastructure, as well as the Cochrane Central Register of Controlled Trials. After evaluation of quality, a meta-analysis of valid extracted data was performed using Review Manager (RevMan software. Five studies with 4,369 patients were included. Bevacizumab plus chemotherapy improved progression-free survival (hazard ratio [HR] =0.63; 95% confidence interval [CI], 0.51–0.77; P<0.01 and overall survival (HR =0.91; 95% CI, 0.84–0.99; P<0.05. Interestingly, in patients with a high risk of progression, the subgroups that received bevacizumab combined with different regimens of chemotherapy showed a significant improvement with paclitaxel plus carboplatin-based chemotherapy (HR =0.86; 95% CI, 0.77–0.95; P<0.01, but not with non-paclitaxel plus carboplatin-based chemotherapy (HR =0.91; 95% CI, 0

Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

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Ivan Novitzky

2016-01-01

Full Text Available To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7 received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16, total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19 were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h bevacizumab injected mice (n=7 they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16 they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03 and sildenafil-treated (p=0.003 groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

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Lassau, N; Coiffier, B; Kind, M; Vilgrain, V; Lacroix, J; Cuinet, M; Taieb, S; Aziza, R; Sarran, A; Labbe-Devilliers, C; Gallix, B; Lucidarme, O; Ptak, Y; Rocher, L; Caquot, L M; Chagnon, S; Marion, D; Luciani, A; Feutray, S; Uzan-Augui, J; Benatsou, B; Bonastre, J; Koscielny, S

2016-10-01

Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. 2007-A00399-44. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

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Toft, Anders; Urup, Thomas; Grunnet, Kirsten

2015-01-01

BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients...... response MRI (RANO criteria). Responders had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS (p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common...... in responders than nonresponders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reducedOS.CONCLUSIONS:Apoor baseline PS and the presence of necrosis were negatively associated...

ELLIPSE Study: a Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia.

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Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Samson, Géraldine; Roux, Adeline; Fargeton, Anne-Emmanuelle; Rioufol, Catherine; Schwiertz, Verane; Disant, François; Chapuis, François; Donazzolo, Yves; Paintaud, Gilles; Edery, Patrick; Faure, Frederic

2014-01-01

Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. ClinicalTrials.gov Identifier #NCT01507480.

Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

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Ping Fang

Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

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Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

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Cuppini, Lucia; Calleri, Angelica; Bruzzone, Maria Grazia; Prodi, Elena; Anghileri, Elena; Pellegatta, Serena; Mancuso, Patrizia; Porrati, Paola; Di Stefano, Anna Luisa; Ceroni, Mauro; Bertolini, Francesco; Finocchiaro, Gaetano; Eoli, Marica

2013-01-01

Background Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB). Methods rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. Results A baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001). Conclusions Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab. PMID:24069296

The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

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Simonds, Jana; Miller, Frank; Mandel, Jess; Davidson, Terence M

2009-05-01

Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. Retrospective pilot study. Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

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Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single use vial

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Perwez Khan

2016-01-01

Full Text Available The risk of endophthalmitis is always a concern when an intraocular procedure is performed. Intravitreal injection is a frequently used method for therapeutic management of many diseases, affecting the posterior segment of the eye. Hence, it is important to assess the risk of complications, especially endophthalmitis. Most studies conducted concentrate on risk assessment from single use from single drug vial. The present article reports the occurrence of cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single vial. Intravitreal injection of bevacizumab was administered to eight eyes of eight patients. Administered dose was prepared from single 4-ml vial of bevacizumab and was injected in the eye, after patient preparation and under aseptic conditions. The procedure was repeated for the remaining patients, thereby imparting multiple pricks in the same vial. Four of the eight patients reported to the hospital on the 3rd day after injection with complaints of pain, watering, and diminution of vision. Two patients reported the following day with similar complaints. Two patients who did not report by the 4th day were contacted and recalled for an examination. All the patients were thoroughly examined using slit lamp biomicroscopy and indirect ophthalmoscopy. Six out of eight were clinically diagnosed to have endophthalmitis and were administered intravitreal antibiotics. The present report highlights possibility of microbial contamination of the drug vial or during compounding process. However, from the present incident, we are encouraged to stay vigilant and wary of contamination

Intravitreal Bevacizumab (Avastin for Diabetic Retinopathy: The 2010 GLADAOF Lecture

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J. Fernando Arevalo

2011-01-01

Full Text Available This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB on diabetic retinopathy (DR including diabetic macular edema (DME and proliferative diabetic retinopathy (PDR at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD, and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

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Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

2014-09-01

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

IS IT POSSIBLE TO USE BEVACIZUMAB BIOSIMILAR IN ALL INDICATIONS REGISTERED FOR ORIGINAL DRUG?

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S. V. Orlov

2016-01-01

Full Text Available The possibility of extrapolation of indications for biosimilars is one of the issues widely discussed in modern literature. Currently, the European Medicines Agency (EMA and the Food and Drug Administration (FDA have identified specific conditions under which for biosimilars extrapolation of indications is possible. In2015, athe first bioanalogue bevacizumab, (produced by JSC "BIOCAD", has been registered. The article provides summary of the pivotal clinical study of Bevacizumab bioanalogue conducted in patients with non-small cell lung cancer. The article includes detailed scientific justification for the extrapolation of data on the efficacy, safety and immunogenicity obtained in the pivotal study to other indications, registered for the original bevacizumab drug.

Fluorescently labeled bevacizumab in human breast cancer: defining the classification threshold

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Koch, Maximilian; de Jong, Johannes S.; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E.; Adams, Arthur L. L.; Kranendonk, Mariëtte E. G.; Terwisscha van Scheltinga, Anton G. T.; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N.; Schröder, Carolien P.; Jorritsma-Smit, Annelies; Linssen, Matthijs D.; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B.; Elias, Sjoerd G.; Oliveira, Sabrina; Witkamp, Arjen J.; Mali, Willem P. Th. M.; Van der Wall, Elsken; Garcia-Allende, P. Beatriz; van Diest, Paul J.; de Vries, Elisabeth G. E.; Walch, Axel; van Dam, Gooitzen M.; Ntziachristos, Vasilis

2017-07-01

In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging.

Intravitreal Bevacizumab: Indications and Complications

International Nuclear Information System (INIS)

Jan, S.; Nazim, M.; Karim, S.; Hussain, Z.

2016-01-01

Background: Bevacizmab is still an unlicensed drug for intraocular use in spite of the fact that it has shown comparable efficacy to other anti-vascular endothelial growth factors (anti-VEGF) medications in some large sample randomized control trails. Although repackaged bevacizumab has got safety concerns but its use is growing because of easy availability and low cost. Our study focuses on the diverse and growing indications of intravitreal bevacizumab (IVB) and its ocular complications in our geographical setting. Method: This interventional case series was carried out at my private practice in Said Anwar Medical Complex, Dabgari, Peshawar, from January 2008 to July 2015. Total of 6107 injections were given to 4352 eyes. Intravitreal bevacizumab was injected in proper operating room setting. Bevacizumab injections were prepared from same vial by multiple withdrawals taking care of aseptic precautions. Follow up was done at 1 week and 20 days and adverse effects were noted. Results: Diabetic macular oedema (36 percent), central retinal vein occlusion (17.6 percent) and branched retinal vein occlusion (11 percent) were the top three indications of IVB. Other common indications were proliferative diabetic retinopathy (9.6 percent), neo-vascular glaucoma (5.9 percent), proliferative diabetic retinopathy with vitreous bleed (4.4 percent), proliferative diabetic retinopathy with tractional retinal detachment (3.7 percent), neo-vascular age related macular degeneration (2.9 percent), central serous retinopathy (1.48 percent) and Eale disease (1.48 percent). Endohthalmitis occurred in 3 eyes (0.069 percent) while retinal detachment was found in only 2 eyes (0.046 percent).Conclusion: Common indications of bevacizumab are diabetic macular oedema, central retinal vein occlusion and branched retinal vein occlusion. Complications like endophthalmitis and retinal detachment are rare. (author)

Intravitreal ranibizumab and bevacizumab for the treatment of nonsubfoveal choroidal neovascularization in age-related macular degeneration Ranibizumab e bevacizumab intravítreo no tratamento da neovascularização de coróide extrafoveal da degeneração macular relacionada à idade

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Aaron Brock Roller

2009-10-01

Full Text Available PURPOSE: To investigate the efficacy of vascular endothelial growth factor-specific (VEGF monoclonal antibodies in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD that does not extend beneath the foveal center (nonsubfoveal CNV. METHODS: The study design was a retrospective chart review of consecutive patients over a two-month period under active treatment with bevacizumab and/or ranibizumab for neovascular AMD. Patients with neovascularization within the macula that did not extend beneath the center of the foveal avascular zone, along with at least one large drusen (>125 µ or many intermediate size (63-124 µ drusen were included. Best corrected Snellen visual acuity and optical coherence tomography (OCT analysis of the central macular thickness was recorded for each visit. Serial injections of bevacizumab and/or ranibizumab were administered until there was resolution of subretinal fluid clinically or by OCT. Data over the entire follow-up period were analyzed for overall visual acuity and OCT changes. All patients had follow-up since diagnosis of at least 6 months (mean=9.6 months. RESULTS: Of the thirteen included patients, eleven had reduction of retinal thickening in the area involved by the CNV. The remaining two patients did not have OCT data available but had no fluid or activity on clinical examination at last follow-up. One patient (8% lost one line of vision; one (8% remained stable, and eleven (84% gained one or more lines of visual acuity. Three patients (23% gained three or more lines. The average treatment outcome for all patients was a gain of 1.7 ± 1.3 lines of Snellen acuity. Both therapeutic agents were effective, with an average gain of 1.6 ± 0.6 lines for patients treated with bevacizumab, 1.5 ± 1.9 lines gained for patients treated with ranibizumab and 2.5 ± 0.7 lines gained in the two patients who received both agents over the course of their treatment. CONCLUSIONS

A case of recipient bed melt and wound dehiscence after penetrating keratoplasty and subconjunctival injection of bevacizumab.

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Bhasin, Purendra; Gujar, Prateek; Bhasin, Priyamvada

2012-11-01

We describe a case of recipient bed melt and wound dehiscence after uneventful penetrating keratoplasty and subconjunctival injection of bevacizumab. Three weeks postoperatively, the patient presented with limbal ischemia, recipient bed melt, and wound dehiscence corresponding to the area of bevacizumab injection. The melt was managed by application of cyanoacrylate glue along with bandage contact lens. Although the graft survived, there was a problem in re-epithelization. This case highlights the need for further studies to elucidate the therapeutic dose, side effects, and correct timing of using bevacizumab with respect to corneal transplant surgery.

Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

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Isis A. S. Brito

2015-01-01

Full Text Available Radiation retinopathy (RR is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab. One must be aware of distant side effects after intravitreal injections.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

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Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Growth of Scytalidium sp. in a counterfeit bevacizumab bottle

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Gerardo Garcia-Aguirre

2013-01-01

Full Text Available After drawing a dose from an closed bevacizumab (Avastin bottle, a fungus-like foreign body was observed inside. Samples from the vial were cultured in Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment was observed after 10 days. The species was identified as Scytalidium sp.Vial, analysis reported that the seal was lacking proper identification measures and that the label, batch number and expiry date did not correspond to a genuine product. Chemical analysis showed no protein, but 3% of polyethylene glycol, citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a significant risk for ophthalmology and oncology patients. The medical community should be aware of this situation in order to enforce adequate preventive measures.

Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

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Moisseiev, Elad; Waisbourd, Michael; Ben-Artsi, Elad; Levinger, Eliya; Barak, Adiel; Daniels, Tad; Csaky, Karl; Loewenstein, Anat; Barequet, Irina S.

2013-01-01

Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. Methods Tw...

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

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REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

2012-01-01

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

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Niho, Seiji; Ohe, Yuichiro; Ohmatsu, Hironobu; Umemura, Shigeki; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

2017-06-01

We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC). Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m 2 twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate. The efficacy/toxicity of switch maintenance chemotherapy with S-1 and S-1+Bev was evaluated separately. The primary end point of this study was the treatment success rate at three months after the start of S-1 treatment. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities. Copyright © 2017. Published by Elsevier B.V.

Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

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Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2009-06-01

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

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Berlin, Jordan D; Feng, Yang; Catalano, Paul; Abbruzzese, James L; Philip, Philip A; McWilliams, Robert R; Lowy, Andrew M; Benson, Al B; Blackstock, A William

2018-01-01

Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated. © 2017 S. Karger AG, Basel.

Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

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Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

2010-01-01

, 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...

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

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Ronald M Bukowski

2010-03-01

Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

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Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

2015-04-01

Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report

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Tsakpinis, Dimitrios; Nasr, Mayssa B; Tranos, Paris; Krassas, Nikos; Giannopoulos, Theodoros; Symeonidis, Chrysanthos; Dimitrakos, Stavros A; Konstas, Anastasios GP

2011-01-01

Purpose The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA). Case report A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months. Results Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels. Conclusion Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy. PMID:22069349

A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX vs CAPOX alone as adjuvant treatment

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Schouten Sander B

2010-10-01

Full Text Available Abstract Background About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX. Methods/design The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall

Clinical study on Bevacizumab for macular edema induced by retinal vein occlusion

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Zhi-Guang Duan

2014-09-01

Full Text Available AIM: To evaluate the safety and efficacy of intravitreal bevacizumab injection in patients with macular edema(MEinduced by retinal vein occlusion(RVO.METHODS: The records of patients treated with intravitreal injection of 1.75mg bevacizumab for ME induced by RVO were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography(OCTand fundus fluorescein angiography(FFA, etc. Best corrected visual acuity(BCVA, intraocular pressure, the change of lens and vitreous, central foveal thickness(CFTwere observed at 1, 2, 3, 6mo after treatment and compared with before treatment. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. All the cases were followed up at least 6mo. An intravitreal injection of bevacizumab(1.75mgwas given at 6wk intervals.RESULTS: Fifty patients(56 eyeswith the average of(57±18.56years old were included. The mean baseline of BCVA, CFT were(logMAR0.82±0.63,(626.5±178.0μm respectively. Although there was no significant decrease in mean CFT at 1wk after injection, the mean BCVA had significant improvement. Followed up at mean 10.26±5.87mo, BCVA, CFT showed significant improvements over baseline values. The statistics of CFT at 1, 2, 3mo after injection were significant differences compared with before injection in each of the three groups. CFT at 1, 3, 12mo after injection were(365.11±23.212μm,(333.42±35.526μm,(267.6±116.8μm, which had a significant difference(PP>0.05. OCT image showed that after injection macular retinal thickness was becoming thinner. FFA showed that after injection macular fluorescein leakage decreased. BCVA was improved by at least two lines in 48 eyes(86%,remained stable in 8 eyes(14%at the last visit. A total of 112 injections were performed and the average number of injections was 1.96 in the group. About 50% of reinjections gained at least two lines of vision improvement at 1

Bevacizumab: an option for refractory epistaxis in hereditary haemorrhagic telangiectasia.

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Amann, Arno; Steiner, Normann; Gunsilius, Eberhard

2015-08-01

Recurrent epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients significantly decreases their quality of life. Treatment in therapy refractory patients is limited although various options have been tested so far. Herein, one patient is described that was treated for HHT for over 20 years with only intermediate benefits. As epistaxis duration and frequency increased continuously, bevacizumab 5 mg/kg was administered every 2 weeks. During the time of treatment (six doses) and up to 3 month afterwards clinical symptoms, blood pressure, cardiac output, pulmonary arterial hypertension (PAH), bleeding duration and frequency were assessed as criteria for treatment benefit. Duration and frequency of epistaxis decreased immediately after the first application resulting in reduced need of blood transfusions. After completion of six cycles, a further decrease in frequency and duration of bleeding was noted. Cardiac output and PAH decreased or remained stable, respectively, during time and after treatment. No increase in blood pressure could be found but a significant increase in heart rate was experienced after completion of all six applications. Unfortunately, the patient died due to a cerebral abscess. Bevacizumab led to an improvement of HHT related epistaxis, refractory to other treatments.

Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

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Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

2015-01-01

The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

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Christoforidis JB

2013-01-01

Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

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Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

2017-07-06

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (12), number of hyperthermia sessions (24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p chemotherapy cycles ( p chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models

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Piao, Yuji; Park, Soon Young; Henry, Verlene; Smith, Bryan D.; Tiao, Ningyi; Flynn, Daniel L.

2016-01-01

Background Glioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy. Methods We investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone. Results In vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone. Conclusions Together, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma. PMID:26965451

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

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Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

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Turpin, Anthony; Paget-Bailly, Sophie; Ploquin, Anne; Hollebecque, Antoine; Peugniez, Charlotte; El-Hajbi, Farid; Bonnetain, Franck; Hebbar, Mohamed

2018-03-01

We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report

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Tsakpinis D

2011-10-01

Full Text Available Dimitrios Tsakpinis1, Mayssa B Nasr1,2, Paris Tranos3, Nikos Krassas1, Theodoros Giannopoulos2, Chrysanthos Symeonidis1, Stavros A Dimitrakos1, Anastasios GP Konstas212nd University Department of Ophthalmology, Papageorgiou Hospital; 2Glaucoma Unit, 1st University, Department of Ophthalmology, AHEPA Hospital, Thessaloniki, Greece; 3Retina Eye Center, Thessaloniki, GreecePurpose: The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA.Case report: A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS. Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months.Results: Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months visual acuity and visual field were at normal levels.Conclusion: Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy.Keywords: arterial retinal macroaneurysm, anti-VEGF, bevacizumab, multilevel hemorrhage

Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

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Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2009-01-01

Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10). Conclusion Tachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved. PMID:19516114

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

International Nuclear Information System (INIS)

Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus; Peck-Radosavljevic, Markus; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus

2017-01-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

Science.gov (United States)

Li, Shuren; Peck-Radosavljevic, Markus; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus; Haug, Alexander; Hacker, Marcus

2017-09-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

Analysis on complications after intravitreal injection of bevacizumab

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Cui-Wei Zhang

2013-08-01

Full Text Available AIM: To observe and analyze on the incidence rate and causes of complications after anintravitreal injection of bevacizumab. METHODS: Totally, 207 cases(207 eyeswith wet age-related macular degeneration were selected randomly. All cases were treated with intravitreal injections of bevacizumab(1.5mg/0.06mLand asked for chief complaints at 1 day, 1 week, 4, 12 weeks after operation, and also examined for routine visual acuity(best corrected visual acuity, BCVA, non-contact tonometer, slit lamp microscope and indirect ophthalmoscope etc.RESULTS: Among 207 cases(207 eyes, visual acuity improved efficiency was 90.8% 12 weeks after treatment, foreign body sensation was found in 7 cases(3.4%, eyelid skin pruritus in 1 case(0.5%, conjunctival congestion in 6 cases(2.9%, subconjunctival hemorrhage in 1 case(0.5%, post-operative intraocular pressure elevation in 2 cases(1.0%. CONCLUSION: The intravitreal injection of bevacizumab is effective with fewer complications. We propose to carry out a further randomized multicenter and larger-sample clinical research and further draw up the clinical application criterion of bevacizumab.

A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

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Erin D. Powell

2009-07-01

Full Text Available A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab.

Which dose of bevacizumab is more effective for the treatment of aggressive posterior retinopathy of prematurity: lower or higher dose?

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Seyhan Dikci

Full Text Available ABSTRACT Purpose: To compare 0.5 mg and 0.625 mg of bevacizumab for treating aggressive posterior retinopathy of prematurity (AP-ROP. Methods: The medical records of patients with AP-ROP who were administered intravitreal bevacizumab (IVB as a primary treatment at a university clinic were evaluated retrospectively. Five eyes of three patients (Group 1 who received 0.625 mg/0.025 ml IVB and 10 eyes of another five patients (Group 2 who received 0.5 mg/0.02 ml IVB were evaluated. Laser photocoagulation was used as additional treatment after relapses. Anatomic results and complications were evaluated in both groups. Results: We evaluated 15 eyes of eight patients (four girls and four boys with a flat demarcation line at posterior zone 2 and plus disease or stage-3 disease in this study. The mean gestational age of the three babies in Group 1 was 26 ± 1 weeks and the mean birth weight was 835.33 ± 48.01 g. The corresponding values were 25.2 ± 1.6 weeks and 724 ± 139.03 g, respectively, for the five babies in Group 2. Retinal vascularization was completed at a mean postmenstrual duration of 53.6 ± 1.5 weeks without additional treatment in the five eyes in Group 1. Laser photocoagulation for relapse was administered to five of the 10 eyes in Group 2. Retinal vascularization was completed at a mean postmenstrual duration of 47.6 ± 1.5 weeks in the remaining five eyes. None of the patients developed complications such as cataract, glaucoma, retinal tear, retinal or vitreous hemorrhage, or retinal detachment. Conclusion: Although lower IVB doses in the treatment of AP-ROP are expected to be safer in terms of local and systemic side effects in premature infants, these patients may require additional treatment with IVB or laser photocoagulation.

The effect of bevacizumab for anterior segment neovascularization after silicone oil removal in eyes with previous vitreoretinal surgery.

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Batman, C; Ozdamar, Y

2010-07-01

To report the outcomes of the use of intracameral bevacizumab for iris neovascularization occurring after silicone oil (SO) removal in eyes undergoing vitreoretinal surgery (VRS). This study included 12 eyes that had iris neovascularization after SO removal. The clinical outcomes of 12 eyes after intravitreal bevacizumab injection were reviewed. There were eight men and four women with an average age of 41.58+/-12.68 years. All eyes had VRS for various vitreoretinal diseases. After the mean follow-up period of 9.7+/-5.3 months, SO removal was performed. Then, the patients were followed for more than 2 months and detailed retinal examinations and intraocular pressure (IOP) were normal during this period, but rubeosis iridis (RI) developed. RI was treated with 1 dose of 1.25 mg bevacizumab into the anterior chamber. After a mean follow-up period of 4.8+/-2.2 months, the regression of iris neovacularization was detected and IOP was below 21 mmHg in all eyes. Anterior segment neovascularization (ASNV) may develop through various mechanisms in patients with VRS after SO removal, and anterior chamber injection of bevacizumab may lead to regression of ASNV.

Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

International Nuclear Information System (INIS)

Berruti, Alfredo; D’Avolio, Antonio; Priola, Adriano Massimiliano; Birocco, Nadia; Amoroso, Vito; Biasco, Guido; Papotti, Mauro; Dogliotti, Luigi; Fazio, Nicola; Ferrero, Anna; Brizzi, Maria Pia; Volante, Marco; Nobili, Elisabetta; Tozzi, Lucia; Bodei, Lisa; Torta, Mirella

2014-01-01

We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration number http://www.clinicaltrials.gov/ct2/show/NCT01203306?term

Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

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Jan, S.; Khan, M.N.; Karim, S.; Khan, M.T.; Hussain, Z.; Khan, S.; Nazim, M.

2010-01-01

Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

[¹⁸F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.

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Marti-Climent, J M; Dominguez-Prado, I; Garcia-Velloso, M J; Boni, V; Peñuelas, I; Toledo, I; Richter, J A

2014-01-01

To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

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Pukhraj Rishi

2012-01-01

Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in Portugal: a retrospective, multicenter study

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Estevinho, Fernanda; Soares, Marta; Azevedo, Isabel; Queiroga, Henrique; Parente, Bárbara; Brito, Ulisses; Teixeira, Encarnação; Sotto-Mayor, Renato; Araújo, António

2012-01-01

Lung cancer is the leading cause of cancer-related mortality. In patients with nonsquamous non-small-cell lung cancer (NSCLC) stage IIIB/IV treatment with chemotherapy plus bevacizumab led to significant improvements in progression-free and median overall survival (OS). To report the experience of five Portuguese centers in treating patients with nonsquamous NSCLC in stage IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity outcomes. This was a retrospective, multicenter study on patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and chemotherapy from November 2007 to August 2010 through special use permits. We reviewed the medical records, registry of demographic characteristics, treatments provided, treatment responses, adverse events, and dates of death. Statistical analysis was performed with SPSS statistics software. Median OS and event-free survival (EFS) were calculated using the Kaplan–Meier method. From an eligible population of 41 patients, 37 participants were registered. Study participants were predominantly male (78.4%) with a median age of 53 years (29–75 years). In total, 83.8% patients had stage IV disease (TNM, 6th Ed.). The OS was 21.5 months (95% confidence interval [CI]: 12.6–30.5] and median EFS was 9.4 months (95% CI9: 7.1–11.7). Hematologic toxicity grade 3/4 occurred in 35.1% of patients, and nonhematologic toxicity in 24.3% patients. One fatal thromboembolic event was recorded (2.7%). The results of chemotherapy plus bevacizumab treatment for nonsquamous NSCLC obtained from the daily clinical practice of the centers involved in this study were similar to those of published clinical trials. Collaboration between the different Portuguese centers is crucial for this kind of study

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

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Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

2011-02-15

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

International Nuclear Information System (INIS)

Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried; Nawatny, Jens; Hoffmann, Thomas K.; Peiper, Matthias; Orth, Klaus; Gerber, Peter Arne; Rusnak, Ethelyn; Lammering, Guido; MAASTRO Clinic, Maastricht

2011-01-01

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

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Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

2015-01-01

Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

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Jeon, Sohee; Lee, Won Ki

2014-01-01

Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

Long-Term Follow-Up of Intravitreal Bevacizumab in Retinal Arterial Macroaneurysm: A Case Report

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Shani Golan

2011-12-01

Full Text Available Purpose: To present the long-term effect of intravitreal bevacizumab (Avastin® therapy in a patient suffering from retinal arterial macroaneurysm. Methods: Case report of a 72-year-old female diagnosed with retinal macroaneurysm in the superior temporal artery leading to macular edema. Functional and morphological data at baseline, 4 weeks, 2 months, and 13 months following treatment with two consecutive intravitreal bevacizumab injections are presented. Results: Best-corrected visual acuity improved from 20/160 at baseline to 20/20 at the3-months follow-up and remained stable through 13 months of follow-up. Central retinal thickness measured by optical coherence tomography decreased from 364 µm at baseline to 248 µm at the 13-months follow-up. No ocular or systemic side effects were detected. Conclusions: Intravitreal bevacizumab therapy may lead to resolution of macular edema associated with retinal macroaneurysm and consequently visual improvement. This treatment may promise a long-lasting effect but warrant further investigation in larger series.

Results of the treatment with intravitreal bevacizumab injection in branch retinal vein occlusion

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Osman Sayýn

2017-06-01

Material and Method: The files of patients who had macular edema caused by branch retinal vein occlusion and who were applied intravitreal bevacizumab injection were studied retrospectively. Visual acuity (logMAR in follow-ups of the patients before and after the injection and the macular thickness values of the quadrant of the occlusion were recorded and the effect of intravitreal bevacizumab on these parameters were analyzed. Results: 24 eyes of 24 patients, 17 of which are male and 7 of which are female, were included in the study. The mean age of the patients were 59.1±7.7. The mean visual acuity prior to the injection was determined to be 0.7±0.5 logMAR, and the mean macular thickness value 489.7±129.6 μm. The mean injection number applied was 1.5±0.7. The mean follow-up time after the injection was 3.5±2.7 months. The mean macular thickness was determined to be 393.1±5.7 μm and mean visual acuity was 0.5±0.1 logMAR in the 1st month. In the last follow-ups of the patients, the mean visual acuity was 0.26±0.28 logMAR and the mean macular thickness value was 317.4±71.5 μm. The increase in visual acuity and decrease in macular thickness between first and last control after the injection was found statistically significant. (p<0.001. Conclusion: The intravitreal bevacizumab injection used in macular edema secondary to BRVO increases visual acuity and decreases macular thickness. [J Contemp Med 2017; 7(2.000: 143-148

Optical Coherence Tomographic and Visual Results at Six Months after Transitioning to Aflibercept for Patients on Prior Ranibizumab or Bevacizumab Treatment for Exudative Age-Related Macular Degeneration (An American Ophthalmological Society Thesis)

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Chan, Clement K.; Jain, Atul; Sadda, Srinivas; Varshney, Neeta

2014-01-01

Purpose: To study optical coherence tomographic (OCT) results and vision at 6 months after transition (post-Tx) from intravitreal bevacizumab and/or ranibizumab to aflibercept for treatment of neovascular age-related macular degeneration (nAMD). The null hypothesis was the lack of improvements in OCT metrics and vision outcome in study eyes at 6 months after transitioning from bevacizumab or ranibizumab to aflibercept. Methods: This retrospective study assessed 6 monthly OCT (Cirrus) data after transitioning to aflibercept for eyes on prior Legacy-ranibizumab, Legacy-bevacizumab, or mixed treatment for nAMD. Outcome measures were subretinal fluid (SRF), cystoid macular edema (CME), pigment epithelial detachment (PED) heights and volumes, central 1- and 3-mm subfield, Macular Volume, and best spectacle and pinhole visual acuity (VA). A single masked investigator performed all OCT measurements. Results: One hundred eighty-nine eyes in 172 patients in Legacy-bevacizumab (95 eyes), Legacy-ranibizumab (84 eyes), or Mixed Group(10 eyes) were switched to aflibercept and followed for 6 months. Significant post-Tx reductions were noted in SRF/CME heights and volumes (all P<.001). Similar findings were noted for PED heights (122.8 μm vs 79.4 μm) and PED volumes (all P<.001). Post-Tx VA was better (20/43 vs 20/51, P<.001). There were no differences between Legacy-bevacizumab and Legacy-ranibizumab groups in OCT and VA changes. Post-Tx VA, SRF/CME, and PED heights and volumes were improved for Nonresponders (suboptimal response to bevacizumab/ranibizumab) (P=.001 to <.001), but not Responders (good responses to same). The only adverse event was a retinal pigment epithelial tear in one eye. Conclusions: Significant improvements in vision and OCT metrics developed in Nonresponders but not in Responders. Post-Tx VA and OCT measures were similar for eyes on prior bevacizumab or ranibizumab. Post-Tx adverse events were uncommon. PMID:25646034

The value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

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Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Peck-Radosavljevic, Markus; Pinter, Matthias [Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna (Austria); Wang, Hao [Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing (China); Nanoff, Christian [Medical University of Vienna, Institute of Pharmacology, Vienna (Austria); Kaczirek, Klaus [Medical University of Vienna, Department of Surgery, Vienna (Austria)

2017-09-15

This prospective study was to investigate the value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [{sup 11}C]-acetate PET, [{sup 18}F]-FDG PET, and combined [{sup 11}C]-acetate and [{sup 18}F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [{sup 11}C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [{sup 18}F]-FDG with [{sup 11}C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

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Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

2015-03-01

Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

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Schefter, Tracey E., E-mail: tracey.schefter@ucdenver.edu [University of Colorado-Denver, Aurora, CO (United States); Winter, Kathryn [RTOG Statistical Center, Philadelphia, PA (United States); Kwon, Janice S. [University of British Columbia and BC Cancer Agency, Vancouver, BC (Canada); Stuhr, Kelly [Anschutz Cancer Pavilion, Aurora, CO (United States); Balaraj, Khalid [King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Yaremko, Brian P. [University of Western Ontario, London Regional Cancer Program, London, ON (Canada); Small, William [The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL (United States); Gaffney, David K. [University of Utah Health Science Center, Salt Lake City, UT (United States)

2012-07-15

Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grade {>=}4 vaginal bleeding or thrombotic event or Grade {>=}3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6-31.4 months).The median age was 45 years (range, 22-80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

International Nuclear Information System (INIS)

Schefter, Tracey E.; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian P.; Small, William; Gaffney, David K.

2012-01-01

Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m 2 ) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grade ≥4 vaginal bleeding or thrombotic event or Grade ≥3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6–31.4 months).The median age was 45 years (range, 22–80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment–related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab

A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration

Science.gov (United States)

Kitchens, John W; Kassem, Nawal; Wood, William; Stone, Thomas W; Isernhagen, Rick; Wood, Edward; Hancock, Brad A; Radovich, Milan; Waymire, Josh; Li, Lang; Schneider, Bryan P

2013-01-01

Purpose To ascertain whether single nucleotide polymorphisms (SNPs) in the Vascular Endothelial Growth factor (VEGFA), Complement Factor H (CFH), and LOC387715 genes could predict outcome to anti-VEGF therapy for patients with age related macular degeneration (AMD). Methods Patients with “wet” AMD were identified by chart review. Baseline optical coherence tomography (OCT) and visual acuity (VA) data, and at least 6 months of clinical follow up after 3 initial monthly injections of bevacizumab or ranibizumab were required for inclusion. Based on OCT and VA, patients were categorized into two possible clinical outcomes: (a) responders and (b) non-responders. DNA was extracted from saliva and genotyped for candidate SNPs in the VEGFA, LOC387715, and CFH genes. Clinical outcomes were statistically compared to patient genotypes. Results 101 patients were recruited, and one eye from each patient was included in the analysis. 97% of samples were successfully genotyped for all SNPs. We found a statistically significant association between the LOC387715 A69S TT genotype and outcome based on OCT. Conclusion Genetic variation may be associated with outcome in patients receiving anti-VEGF therapy. PMID:24143065

RISK FOR LOW VISUAL ACUITY AFTER 1 AND 2 YEARS OF TREATMENT WITH RANIBIZUMAB OR BEVACIZUMAB FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Westborg, Inger; Albrecht, Susanne; Rosso, Aldana

2017-11-01

To investigate how patients with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab respond to treatment in daily clinical practice. Data from the Swedish Macula Register on the treatment received by 3,912 patients during 2011 to 2014 is reported. Patients' characteristics at the first visit, visual acuity, number of injections, and reason for terminating the treatment if applicable are discussed. Furthermore, the risk of having poor vision (visual acuity under 60 Early Treatment Diabetes Retinopathy Study letters or approximately 20/60 Snellen) is calculated for the treated eye after 1 year and 2 years. The treatment outcome depends on the visual acuity at the first visit. For patients with visual acuity more than 60 letters, the risk of having a visual acuity lower than 60 letters after 1 year or 2 years of treatment is approximately 20%. However, for patients with low visual acuity at diagnosis (fewer than 60 letters), the risk is approximately 60%. The risk of having a visual acuity lower than 60 letters does not depend on the choice of treatment drug. Treatment with anti-vascular endothelial growth factor intravitreal injections mainly maintains the visual acuity level, and only approximately 20% and 40% of the patients required vision rehabilitation after 1 year and 2 years, respectively.

Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

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Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

2011-01-01

Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

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Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

2017-08-01

Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of multifocal central nervous system AIDS-related Epstein Barr virus-associated malignant myopericytoma with bevacizumab

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Linda Szymanski

2017-09-01

Full Text Available A 31 year-old man with HIV and pulmonary tuberculosis (TB status-post RIPE regimen presented with cough and throbbing headaches. Laboratory results were remarkable for a CD4 count of 2 kcells/L and a viral load of 2.7 million copies/mL. MRI of the brain reported multiple lobulated and cystic intracranial lesions associated with the dura that had thick rinds of enhancement. CT of the chest, abdomen and pelvis demonstrated axillary and inguinal lymphadenopathy, a mass within the right pelvis thought to represent necrotic lymph nodes, prominence of the right psoas muscle, a cystic nodule in the liver, and a right adrenal lesion. The patient was started on dexamethasone, RIPE therapy, and empiric antimicrobial therapy. He subsequently underwent stealth-guided brain biopsy and open craniotomy. Pathology returned a tissue diagnosis of an AIDS related EBV-associated smooth muscle tumor (EBV-SMT best categorized as a malignant myopericytoma. Following surgery, the patient began additional anti-retroviral therapy for HIV and was discharged. Despite treatment, three to four months following discharge the patient's symptoms progressed and he was found to have developed a severe bilateral homonymous hemianopsia. Repeat MRI demonstrated tumor growth and the patient subsequently received whole brain radiation along with sirolimus and pomalidomide. Approximately two months following radiation therapy the patient had increasing headaches along with nausea and vomiting. Repeat MRI was consistent with radiation arrested tumor growth but did not show any decrease in size of his intracranial lesions. Therapy with bevacizumab was initiated and he had marked improvement of his visual field deficits. The patient has since completed 20 cycles of treatment with bevacizumab and is currently 17 months post his initial diagnosis. Repeat imaging has demonstrated decreasing size of his lesions and no new lesions have developed.

65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer

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Schuette W

2017-11-01

Full Text Available Wolfgang Schuette,1 Claus-Peter Schneider,2,3 Walburga Engel-Riedel,4 Christian Schumann,5,6 Martin Kohlhaeufl,7 Monika Heidi Ursel Serke,8 Gert Hoeffken,9 Cornelius Kortsik,10 Martin Reck11 1Department of Internal Medicine II, Hospital Martha-Maria Halle-Doelau, Halle, 2Department of Pneumonology, Central Hospital, Bad Berka, 3Department of Internal Medicine, DRK Manniske Hospital, Bad Frankenhausen, 4Cologne Clinics, Merheim Lung Hospital, Cologne, 5Pneumonology, Department of Internal Medicine II, University Hospital Ulm, 6Clinic for Pneumology, Thoracic Oncology, Sleep, and Respiratory Critical Care, Kempten-Oberallgäu, 7Center of Pneumonology and Chest Surgery, Hospital Schillerhoehe, Gerlingen, 8Pneumonology, Lung Clinics, Hemer, 9Center of Pneumonology, Chest and Vascular Surgery, Specialty Hospital Coswig, Coswig, 10Department of Pneumonology, Catholic Hospital, Mainz, 11Department of Thoracic Oncology, Lung Clinic, Grosshansdorf, Germany Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem versus carboplatin/pemetrexed plus bevacizumab (BevCPem in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC.Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119 or BevCPem (n=134. The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG performance status (PS.Results: Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864. Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0–1 (median

Efficacy and safety assessment of the addition of bevacizumab to adjuvant therapy agents in cancer patients: A systematic review and meta-analysis of randomized controlled trials

NARCIS (Netherlands)

Ahmadizar, Fariba; Onland-Moret, N. Charlotte; De Boer, Anthonius; Liu, Geoffrey; Maitland-Van Der Zee, Anke H.

2015-01-01

Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

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Ioannis Kapelakis

2017-05-01

Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema

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Kiss S

2014-08-01

Full Text Available Szilárd Kiss,1 Ying Liu,2 Joseph Brown,3 Nancy M Holekamp,4,5 Arghavan Almony,6 Joanna Campbell,2 Jonathan W Kowalski2 1Weill Cornell Medical College, New York, NY; 2Allergan, Inc., Irvine, CA; 3IMS Health, Woodland Hills, CA; 4Pepose Vision Institute, Chesterfield, MO; 5Washington University School of Medicine, St Louis, MO; 6Carolina Eye Associates, Southern Pines, NC, USA Purpose: To examine the utilization of bevacizumab and ranibizumab and disease monitoring in patients with branch or central retinal vein occlusion (BRVO/CRVO or diabetic macular edema (DME in clinical practice.Patients and methods: This retrospective claims analysis included newly diagnosed patients with one or more bevacizumab or ranibizumab injections. Bevacizumab or ranibizumab utilization was assessed by year of first injection: 2008–2010 cohorts (12-month follow-up, January to June 2011 cohort (6-month follow-up. The main outcome measures were mean annual numbers of injections, ophthalmologist visits and optical coherence tomography examinations, and proportion of patients with additional laser or intravitreal triamcinolone (IVTA use.Results: A total of 885 BRVO, 611 CRVO, and 2,733 DME patients treated with bevacizumab were included, with too few ranibizumab-treated patients for meaningful analysis. Across the 2008, 2009, and 2010 cohorts, mean annual numbers of bevacizumab injections increased, but remained low (BRVO 2.5, 3.1, 3.3; CRVO 3.1, 3.1, 3.5; and DME 2.2, 2.5, 3.6, respectively; mean ophthalmologist visits ranged between 4.4 and 6.5, and mean optical coherence tomography examinations ranged between 3.1 and 3.9 across all conditions. A total of 42.0% of BRVO, 16.5% of CRVO, and 57.7% of DME patients received additional laser or IVTA therapy. The number of bevacizumab injections was positively associated with laser use in BRVO (3.3 versus 2.9, P<0.03, and with laser or IVTA use in DME (laser, 3.3 versus 2.7, P<0

Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

Science.gov (United States)

Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

2013-01-01

The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3.

Science.gov (United States)

Modest, D P; Denecke, T; Pratschke, J; Ricard, I; Lang, H; Bemelmans, M; Becker, T; Rentsch, M; Seehofer, D; Bruns, C J; Gebauer, B; Modest, H I; Held, S; Folprecht, G; Heinemann, V; Neumann, U P

2018-01-01

The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. CLINICALTRIALS. NCT00433927. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

Science.gov (United States)

Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

International Nuclear Information System (INIS)

Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

2016-01-01

To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis.

Science.gov (United States)

Tomasello, Gianluca; Petrelli, Fausto; Ghidini, Michele; Russo, Alessandro; Passalacqua, Rodolfo; Barni, Sandro

2017-07-13

The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions. A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer). Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded. Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial. Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions. Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30

Vincristine, Irinotecan, and Bevacizumab in Relapsed Wilms Tumor With Diffuse Anaplasia.

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Schiavetti, Amalia; Varrasso, Giulia; Collini, Paola; Clerico, Anna

2018-05-01

The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.

Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

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Macedo Ligia

2012-03-01

Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

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Walker Mark S

2012-06-01

Full Text Available Abstract Background Bevacizumab (B and cetuximab (C are both approved for use in the treatment of metastatic colorectal cancer (mCRC in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O and who had completed ≥ 1 Patient Care Monitor (PCM surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference. Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38. Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6. Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1% and FOLFOX ± B or C (22.5%. Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s  Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.

Combination of Laser Photocoagulation and Intravitreal Bevacizumab in Aggressive Posterior Retinopathy of Prematurity.

Science.gov (United States)

Altinsoy, Halil Ibrahim; Mutlu, Fatih Mehmet; Güngör, Riza; Sarici, S Ümit

2010-03-09

The response to combined laser photocoagulation and a single intravitreal injection of 0.75 mg bevacizumab to each eye on separate days in two patients with aggressive, posterior retinopathy of prematurity (ROP) is described. Combined treatment resulted in regression of zone-1 disease in Case 1, which had no retinal detachment. However, no significant regression or unfavorable anatomic response was observed in the second case with retinal detachment. Although the combination of laser photocoagulation and intravitreal bevacizumab injection seems to be well tolerated, inducing prompt regression of agressive zone-1 ROP without retinal detachment, further controlled studies with long-term follow-up are necessary for their use in the treatment of ROP with for potentially dangerous growth factor inhibitors in premature babies. Copyright 2010, SLACK Incorporated.

RTOG 0417: Efficacy of Bevacizumab in Combination With Definitive Radiation Therapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma

International Nuclear Information System (INIS)

Schefter, Tracey; Winter, Kathryn; Kwon, Janice S.; Stuhr, Kelly; Balaraj, Khalid; Yaremko, Brian Patrick; Small, William; Sause, William; Gaffney, David

2014-01-01

Purpose: Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS). Methods and Materials: Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m 2 ) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method. Results: 49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively. Conclusion: In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical cancer

A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

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Hiroki Hashida

2017-01-01

Full Text Available It has been reported that many patients with lung metastasis of colorectal cancer (CRC underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI plus bevacizumab (BV therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped.

Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma.

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Hicks, Martin J; Funato, Kosuke; Wang, Lan; Aronowitz, Eric; Dyke, Jonathan P; Ballon, Douglas J; Havlicek, David F; Frenk, Esther Z; De, Bishnu P; Chiuchiolo, Maria J; Sondhi, Dolan; Hackett, Neil R; Kaminsky, Stephen M; Tabar, Viviane; Crystal, Ronald G

2015-01-01

The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.

Phase II Study of Long-Term Androgen Suppression With Bevacizumab and Intensity-Modulated Radiation Therapy (IMRT) in High-Risk Prostate Cancer

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Vuky, Jacqueline, E-mail: vukyja@ohsu.edu [Section of Community Hematology/Oncology, Knight Cancer Institute, Oregon Health Sciences University, Portland, OR (United States); Pham, Huong T. [Section of Hematology/Oncology and Radiation Oncology, Virginia Mason Medical Center, Seattle, WA (United States); Warren, Sarah; Douglass, Erika [Benaroya Research Institute, Virginia Mason Medical Center, Seattle, WA (United States); Badiozamani, Kasra [Section of Hematology/Oncology and Radiation Oncology, Virginia Mason Medical Center, Seattle, WA (United States); Madsen, Berit; Hsi, Alex [Peninsula Cancer Center, Poulsbo, WA (United States); Song Guobin [Section of Hematology/Oncology and Radiation Oncology, Virginia Mason Medical Center, Seattle, WA (United States)

2012-03-15

Purpose: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. Methods and Materials: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. Results: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). Conclusions: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be

Phase II Study of Long-Term Androgen Suppression With Bevacizumab and Intensity-Modulated Radiation Therapy (IMRT) in High-Risk Prostate Cancer

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Vuky, Jacqueline; Pham, Huong T.; Warren, Sarah; Douglass, Erika; Badiozamani, Kasra; Madsen, Berit; Hsi, Alex; Song Guobin

2012-01-01

Purpose: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. Methods and Materials: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. Results: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28–40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). Conclusions: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

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Bukowski, Ronald M

2010-01-01

The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

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Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

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Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

2015-07-01

This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

Iodogen-mediated radiolabeling of Bevacizumab with I-123 for clinical applications

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Lemps, R. de; Desruet, M.; Bacot, S.; Ahmadi, M.; Ghezzi, C.; Desruet, M.; Fagret, D.; Berger, F.

2014-01-01

Bevacizumab is a monoclonal antibody, directed against vascular endothelial growth factor (VEGF), and is currently used in various types of cancers (breast, lung, colorectal). In order to administer to humans glioblastomas, we developed its iodine 123 radiolabeling for in vitro and in vivo studies subsequent. The aim of the study is to choose the best radioiodination conditions based on feasibility in a hospital radiopharmacy: Quick one step method under mild condition, reproducible, using materials for pharmaceutical use and in a closed-system. Method Bevacizumab was radiolabeled with "1"2"3I using Iodogen, the most widely used oxidants in direct labelling techniques for tyrosyl residues-containing compounds. We have been explored two crucial parameters for clinical transfer: the amount of oxidant required (50μg and 100μg) and the choice of the purification column (size exclusion column or anion exchange resin), respectively. Quality control was performed before and after purification of each condition in order to evaluate the radiochemical purity (RCP) and purification efficiency. The stability of the radiolabeled molecule is evaluated over time and also when the solution is diluted with unlabeled bevacizumab. Moreover, the in vitro stability of "1"2"3I-bevacizumab was determined in presence of human blood at 15, 30, 60 and 120 min. Labeling yield before purification was 96.5% for the first condition (50μg Iodogen) and 95.5% for the second one (100μg Iodogen). The radiochemical purity was 99.5% after purification on a size exclusion column and 99% after purification on anion exchange resin. The purification yield with size exclusion column is 75%, compared with 81% of the anionic exchange resin. The stability in the labeling medium of "1"2"3I-bevacizumab at 3, 6, 24 and 30 h after labeling showed a RCP at 100%, 93%, 99.8% and 99.8% for condition 1 so that it was found to be 99.2%, 100%, 99.3%, 99.5% for condition 2, respectively. In vitro incubation with

Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

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Glynne-Jones, R.; Hava, N.; Goh, V.; Bosompem, S.; Bridgewater, J.

2015-01-01

In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT

Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab

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Madsen Christine

2012-09-01

Full Text Available Abstract Introduction Anti-VEGF treatment has proven effective in recurrent ovarian cancer. However, the identification of the patients most likely to respond is still pending. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF system and the fibroblast growth factor (FGF system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment. The aim of the present study was to investigate if potential changes of PDGF-BB, PDGF-AA, and FGF2 before and during bevacizumab treatment had predictive value for early progression or survival. Furthermore, we wanted to investigate the importance of serum VEGF in the same cohort. Methods This study included 106 patients with chemotherapy-resistant epithelial ovarian cancer who were treated with single agent bevacizumab as part of a biomarker protocol. Patients were evaluated for response by the Response Evaluation Criteria In Solid Tumors (RECIST and/ or Gynecologic Cancer Intergroup (GCIG CA125 criteria. Serum samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB, PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF-BB, PDGF-AA analysis, and 93 baseline samples for VEGF. Results High baseline serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB and FGF2 was of prognostic significance. None of the markers showed predictive value, neither at baseline level nor during the treatment.

Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer

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Makondi, Precious Takondwa; Lee, Chia-Hwa; Huang, Chien-Yu; Chu, Chi-Ming; Chang, Yu-Jia

2018-01-01

can be potential targets and predictors of therapeutic resistance and prognosis in bevacizumab-treated patients with mCRC. PMID:29342159

Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer.

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Precious Takondwa Makondi

can be potential targets and predictors of therapeutic resistance and prognosis in bevacizumab-treated patients with mCRC.

Innovative methods for the identification of predictive biomarker signatures in oncology: Application to bevacizumab

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Paul Delmar

2017-03-01

Full Text Available Current methods for subgroup analyses of data collected from randomized clinical trials (RCTs may lead to false-positives from multiple testing, lack power to detect moderate but clinically meaningful differences, or be too simplistic in characterizing patients who may benefit from treatment. Herein, we present a general procedure based on a set of newly developed statistical methods for the identification and evaluation of complex multivariate predictors of treatment effect. Furthermore, we implemented this procedure to identify a subgroup of patients who may receive the largest benefit from bevacizumab treatment using a panel of 10 biomarkers measured at baseline in patients enrolled on two RCTs investigating bevacizumab in metastatic breast cancer. Data were collected from patients with human epidermal growth factor receptor 2 (HER2-negative (AVADO and HER2-positive (AVEREL metastatic breast cancer. We first developed a classification rule based on an estimated individual scoring system, using data from the AVADO study only. The classification rule takes into consideration a panel of biomarkers, including vascular endothelial growth factor (VEGF-A. We then classified the patients in the independent AVEREL study into patient groups according to “promising” or “not-promising” treatment benefit based on this rule and conducted a statistical analysis within these subgroups to compute point estimates, confidence intervals, and p-values for treatment effect and its interaction. In the group with promising treatment benefit in the AVEREL study, the estimated hazard ratio of bevacizumab versus placebo for progression-free survival was 0.687 (95% confidence interval [CI]: 0.462–1.024, p = 0.065, while in the not-promising group the hazard ratio (HR was 1.152 (95% CI: 0.526–2.524, p = 0.723. Using the median level of VEGF-A from the AVEREL study to divide the study population, then the HR becomes 0.711 (95% CI: 0.435–1.163, p = 0

Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

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P William Conrad

2008-06-01

Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion.

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Tamiya, Motohiro; Tamiya, Akihiro; Yasue, Tomomi; Nakao, Keiko; Omachi, Naoki; Shiroyama, Takayuki; Tani, Eriko; Hamaguchi, Masanari; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Okishio, Kyoichi; Kawaguchi, Tomoya; Atagi, Shinji; Hirashima, Tomonori

2016-06-01

Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF. Therefore, this study evaluated whether plasma or pleural effusion VEGF might predict bevacizumab treatment outcome. We enrolled 23 patients with NSCLC and MPE between September 2010 and June 2012. Plasma VEGF levels were measured in 19 patients and pleural VEGF levels were measured in 22 patients. Compared to patients with a low plasma VEGF level, patients with a high level exhibited significantly shorter overall survival (OS: 13.8 vs. 6.5 months, p=0.04), progression-free survival (PFS: 8.7 vs. 4.8 months, peffusion, patients with a high VEGF level exhibited significantly shorter OS (19.6 vs. 6.9 months, peffusion may predict the outcome of bevacizumab treatment in patients with NSCLC and MPE. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

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Tugba Cakmak Argun

2017-07-01

Full Text Available AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.

Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab.

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Nelson, Sarah J; Li, Yan; Lupo, Janine M; Olson, Marram; Crane, Jason C; Molinaro, Annette; Roy, Ritu; Clarke, Jennifer; Butowski, Nicholas; Prados, Michael; Cha, Soonmee; Chang, Susan M

2016-10-01

Interpretation of changes in the T1- and T2-weighted MR images from patients with newly diagnosed glioblastoma (GBM) treated with standard of care in conjunction with anti-angiogenic agents is complicated by pseudoprogression and pseudoresponse. The hypothesis being tested in this study was that 3D H-1 magnetic resonance spectroscopic imaging (MRSI) provides estimates of levels of choline, creatine, N-acetylaspartate (NAA), lactate and lipid that change in response to treatment and that metrics describing these characteristics are associated with survival. Thirty-one patients with newly diagnosed GBM and being treated with radiation therapy (RT), temozolomide, erlotinib and bevacizumab were recruited to receive serial MR scans that included 3-D lactate edited MRSI at baseline, mid-RT, post-RT and at specific follow-up time points. The data were processed to provide estimates of metrics representing changes in metabolite levels relative to normal appearing brain. Cox proportional hazards analysis was applied to examine the relationship of these parameters with progression free survival (PFS) and overall survival (OS). There were significant reductions in parameters that describe relative levels of choline to NAA and creatine, indicating that the treatment caused a decrease in tumor cellularity. Changes in the levels of lactate and lipid relative to the NAA from contralateral brain were consistent with vascular normalization. Metabolic parameters from the first serial follow-up scan were associated with PFS and OS, when accounting for age and extent of resection. Integrating metabolic parameters into the assessment of patients with newly diagnosed GBM receiving therapies that include anti-angiogenic agents may be helpful for tracking changes in tumor burden, resolving ambiguities in anatomic images caused by non-specific treatment effects and for predicting outcome.

Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

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Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Chan, Kelvin K W; Virik, Kiran; Hammerman, Ariel; Brenner, Baruch; Flowers, Christopher R; Hall, Peter S

2017-06-01

In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel. © AlphaMed Press 2017.

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

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Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

2018-06-09

Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 plus Bevacizumab

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Satoshi Otsu

2014-01-01

Full Text Available This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE (version 3.0. The evaluation was especially focused on grade 2 oxaliplatin-induced neuropathy. The estimated median treatment time to occurrence of grade 2 sensory neuropathy was 7.3 months. The estimated median cumulative dose to occurrence of grade 2 sensory neuropathy was 931 mg/m 2 . This study clarified the treatment time from first dose as well as the cumulative dose of oxaliplatin leading to grade 2 neuropathy. It may be important to institute some clinical countermeasures when grade 2 neuropathy occurs so as to reduce the chance of progression to irreversible grade 3 neuropathy.

Bevacizumab compared with Diode Laser in stage 3 posterior retinopathy of prematurity: a 5 year follow-up

LENUS (Irish Health Repository)

O’Keeffe, N

2016-02-01

We conducted a prospective randomized study to compare outcomes of intravitreal Bevacizumab versus diode laser in thirty eyes of fifteen premature babies with zone 1 or posterior zone 2 retinopathy of prematurity (ROP). We recorded complications, regression\\/reactivation of ROP, visual outcome, refractive error and systemic complications. The Bevacizumab-treated eyes showed rapid regression of the ROP with resolution of plus disease and flattening of the ridge at 48 hours post injection. In 3 Bevacizumab-treated eyes, reactivation occurred and were treated with laser (3 eyes) or a further Bevacizumab injection (1 eye). Of the diode laser treated eyes, one showed progression and was treated with Bevacizumab. At 5-year follow-up, good outcomes were observed in both treatment groups. However, less myopia was found in the Bevacizumab compared with the diode laser treated eyes.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

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Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

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Suenaga M

2015-03-01

Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

Science.gov (United States)

Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

2013-05-01

Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

[A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].

Science.gov (United States)

Mori, Ayano; Kogawa, Takahiro; Arihara, Youhei; Abe, Masakazu; Tamura, Fumito; Abe, Seiichirou; Kukitsu, Takehiro; Ihara, Hideyuki; Sumiyoshi, Tetsuya; Yoshizaki, Naoto; Kondou, Hitoshi; Tsuji, Yasushi

2013-05-01

A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

Science.gov (United States)

Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

2018-01-01

Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

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Lee, Koon-Ja; Lee, Ji-Young; Lee, Sung Ho; Choi, Tae Hoon

2013-01-01

To understand the corneal regeneration induced by bevacizumab, we investigated the structure changes of stroma and basement membrane regeneration. A Stick soaked in 0.5 N NaOH onto the mouse cornea and 2.5 mg/ml of bevacizumab was delivered into an alkali-burned cornea (2 μl) by subconjunctival injections at 1 hour and 4 days after injury. At 7 days after injury, basement membrane regeneration was observed by transmission electron microscope. Uneven and thin epithelial basement membrane, light density of hemidesmosomes, and edematous collagen fibril bundles are shown in the alkali-burned cornea. Injured epithelial basement membrane and hemidesmosomes and edematous collagen fibril bundles resulting from alkali-burned mouse cornea was repaired by bevacizumab treatment. This study demonstrates that bevacizumab can play an important role in wound healing in the cornea by accelerating the reestablishment of basement membrane integrity that leads to barriers for scar formation. [BMB Reports 2013; 46(4): 195-200] PMID:23615260

A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus Bevacizumab

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Masayasu Naito

2014-07-01

Full Text Available A 61-year-old male, who had been admitted to another hospital due to disseminated intravascular coagulation (DIC, was referred to our hospital. Total colonoscopy, abdominal dynamic CT and positron-emission tomography revealed bone metastasis and multiple lymphocytic metastases from transverse colon cancer in addition to disseminated carcinomatosis of the bone marrow (DCBM. We immediately performed chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse colon cancer in order to avoid radical surgery. In addition, we initiated the administration of recombinant human soluble thrombomodulin for 1 week to treat DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy without any severe side effects. After receiving the 4 cycles of treatment, he recovered from DIC, and the bone and multiple lymphocytic metastases disappeared.

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

OpenAIRE

Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-01-01

Introduction Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. Methods First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligam...

In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

NARCIS (Netherlands)

Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

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Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

2018-05-01

Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

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Eric K. Newcott

2015-01-01

Full Text Available Purpose. To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment. Methods. We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye. Results. Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision. Conclusion. Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

Efficacy of intra-meibomian gland injection of the anti-VEGF agent bevacizumab for the treatment of meibomian gland dysfunction with lid-margin vascularity

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Jiang X

2018-05-01

Full Text Available Xiaodan Jiang,* Yuexin Wang,* Huibin Lv, Yan Liu, Mingzhou Zhang, Xuemin Li Department of Ophthalmology, Peking University Third Hospital, Beijing, China *These authors contributed equally to this work Purpose: To investigate the efficacy of a novel treatment – intra-meibomian gland (MG injection of the anti-VEGF agent bevacizumab – for MG dysfunction (MGD with eyelid-margin vascularity. Methods: A total of 26 eyes from 13 patients diagnosed with MGD and eyelid-margin vascularity were included in our study. Patients received intra-meibomian gland injections of bevacizumab (150 µL, 2.5 mg/0.1 mL at multiple sites with a 29 G needle where telangiectasia was severe. The Ocular Surface Disease Index (OSDI, tear film, tear-breakup time (TBUT, eyelid-margin features, MG features, conjunctiva, and corneal staining were assessed at 1 day before injection and 1 week, 1 month, and 3 months after injection. Blood pressure, best-corrected visual acuity, intraocular pressure, and slit lamp examinations were performed to assure the safety of patients at 1 day before and 1 day, 1 week, 1 month, and 3 months after injection. Results: Lid-margin vascularity, conjunctival injection, expressed secretion quality, expressivity of the MG, TBUT, corneal staining, and OSDI were significantly improved 1 week, 1 month, and 3 months after injection compared to baseline values. Lid-margin vascularity, conjunctival injection, meibomian gland expressivity, TBUT, and OSDI continued to improve; the greatest improvements were observed at 1 month and sustained for 3 months. Spearman’s correlation analysis indicated that age and sex significantly influenced TBUT improvement. Females and older patients tended to have shorter baseline TBUT that followed a different trend from that of males and younger patients during postinjection visits, revealed by subgroup analysis. No local or systemic side effects were observed at follow-up visits. Conclusion: This study is the first to

A Feasibility Study of Bevacizumab Plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

Science.gov (United States)

McArthur, Heather L.; Rugo, Hope; Nulsen, Benjamin; Hawks, Laura; Grothusen, Jill; Melisko, Michelle; Moasser, Mark; Paulson, Matthew; Traina, Tiffany; Patil, Sujata; Zhou, Qin; Steingart, Richard; Dang, Chau; Morrow, Monica; Cordeiro, Peter; Fornier, Monica; Park, John; Seidman, Andrew; Lake, Diana; Gilewski, Theresa; Theodoulou, Maria; Modi, Shanu; D’Andrea, Gabriella; Sklarin, Nancy; Robson, Mark; Moynahan, Mary Ellen; Sugarman, Steven; Sealey, Jane E.; Laragh, John H.; Merali, Carmen; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

2016-01-01

Purpose Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin–cyclophosphamide (ddAC)→nanoparticle albumin−bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC→nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results The median age was 48 years (range, 27−75 years), and baseline LVEF was 68% (53%−82%). After 39 months’ median follow-up (5−45 months): median LVEF was 68% (53%−80%) at 2 months (n=78), 64% (51%−77%) at 6 months (n=66), 63% (48%−77%) at 9 months (n=61), and 66% (42%−76%) at 18 months (n=54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted CHF or HTN, respectively. Conclusions Bevacizumab with ddAC→nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials. PMID:21350003

CCR 20th Anniversary Commentary: Bevacizumab in the Treatment of Glioblastoma--The Progress and the Limitations.

Science.gov (United States)

Mar, Nataliya; Desjardins, Annick; Vredenburgh, James J

2015-10-01

Vredenburgh and colleagues conducted the first phase II study of bevacizumab plus irinotecan in recurrent malignant glioma, confirming the safety and efficacy of bevacizumab. This study, which was published in the February 15, 2007, issue of Clinical Cancer Research, was a stepping stone for subsequent research, leading to regulatory approval of bevacizumab for recurrent glioblastoma. ©2015 American Association for Cancer Research.

[A case of transverse colon cancer with multiple liver metastases and hepatic pedicle lymph node involvement showing pathological complete response by XELOX plus bevacizumab].

Science.gov (United States)

Mukai, Toshiki; Akiyoshi, Takashi; Koga, Rintaro; Arita, Junichi; Saiura, Akio; Ikeda, Atsushi; Nagasue, Yasutomo; Oikawa, Yoshinori; Yamakawa, Keiko; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi; Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Yamamoto, Chiriko; Yamaguchi, Toshiharu

2012-12-01

A 70-year-old woman was referred to our hospital because of abdominal pain. Abdominal computed tomography(CT)and colonoscopy revealed transverse colon cancer with multiple liver metastases, with involvement of the hepatic pedicle and superior mesenteric artery lymph nodes. The patient received eight courses of XELOX plus bevacizumab, and CT showed a decrease in the size of the liver metastases and hepatic pedicle lymphadenopathy. Right hemicolectomy, partial hepatectomy, and hepatic pedicle lymph node resection were performed. Histopathological examination of the resected tissue revealed no residual cancer cells, suggesting a pathological complete response. The patient remains well 7 months after operation, without any signs of recurrence. Surgical resection should be considered for patients with initially unresectable colon cancer with liver metastases and hepatic pedicle lymph nodes involvement if systemic chemotherapy is effective.

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

International Nuclear Information System (INIS)

Britten, Carolyn D; Gomes, Antoinette S; Wainberg, Zev A; Elashoff, David; Amado, Rafael; Xin, Yan; Busuttil, Ronald W; Slamon, Dennis J; Finn, Richard S

2012-01-01

Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation

Esophageal Metastasis from Rectal Cancer Successfully Treated with Fluorouracil-Based Chemotherapy with Bevacizumab: A Case Report and Review of the Literature

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Sho Watanabe

2017-05-01

Full Text Available Esophageal metastasis from colorectal carcinoma is uncommon, and diagnosis of esophageal metastasis is difficult. We report a case of a 54-year-old woman with postoperative recurrence of rectal cancer metastasizing to the esophagus. She underwent rectectomy and adjuvant chemotherapy with fluorouracil, leucovorin plus oxaliplatin for stage IIIB rectal cancer. Three years later, she presented with dysphagia and cough. Computed tomography showed thickening of the esophagus wall, enlargement of the lymph nodes in the mediastinum and abdomen, and ground-glass opacities in the right lung. Endoscopy revealed a submucosal tumor of the midthoracic esophagus. Histopathological analysis of the tumor biopsy showed infiltration of adenocarcinoma cells into the stroma of the esophagus; tumor cells were positive for caudal type homeobox 2 and negative for thyroid transcription factor 1. A transbronchial biopsy indicated pulmonary lymphangitic carcinomatosis of rectal adenocarcinoma. Based on those findings, she was diagnosed with recurrent rectal cancer. She received fluorouracil-based chemotherapy plus bevacizumab, which ameliorated her symptoms and induced a durable response without severe adverse events. Diagnosis of esophageal metastasis from rectal cancer can thus be made by repeated biopsy. Furthermore, aggressive systemic treatment with fluorouracil-containing chemotherapy and bevacizumab is a treatment option for colorectal cancer patients with esophageal metastasis.

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

Science.gov (United States)

Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

2015-02-01

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Indications and Treatment Outcomes of Intravitreal Bevacizumab ...

African Journals Online (AJOL)

Bevacizumab and Ranibizumab for Retinal Diseases in Benin. City, Nigeria. Odarosa M. .... travel costs and risk of complications such as endophthalmitis and retinal detachment ... antiVEGF to be utilised considering reports of increased risk of.

Simultaneous application of bevacizumab and anti-CTGF antibody effectively suppresses proangiogenic and profibrotic factors in human RPE cells.

Science.gov (United States)

Bagheri, Abouzar; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Sheibani, Nader; Astaneh, Shamila Darvishalipour; Kanavi, Mozhgan Rezaei; Mohammadian, Azam

2015-01-01

Retinal pigment epithelial (RPE) cells play key roles in the development of choroidal neovascularization and subsequent fibrosis. We investigated the impact of bevacizumab, antihuman vascular endothelial growth factor (VEGF) antibody, and anticonnective tissue growth factor (anti-CTGF) neutralizing antibody, individually or in combination, on proangiogenic and profibrotic properties of RPE cells. Primary cultures of human RPE cells were incubated with different concentrations of bevacizumab (0.25, 0.5, and 0.8 mg/ml) and/or anti-CTGF (10 μg/ml), and cell proliferation and apoptosis were determined. Expression and activity of proangiogenic and profibrotic genes including matrix metalloproteinases (MMP)-2 and 9, VEGFA, CTGF, vascular endothelial growth factor receptor-1 (VEGFR-1), cathepsin D, tissue inhibitor of metalloproteinases (TIMP) -1 and -2, and alpha smooth muscle actin (α-SMA) were assessed with slot blot, real-time RT-PCR, and zymography. Bevacizumab alone inhibited proliferation of RPE cells while anti-CTGF or bevacizumab and anti-CTGF combined had no inhibitory effect in this regard. Bevacizumab increased MMP-2, MMP-9, and cathepsin D but decreased VEGFA and VEGFR-1 expression. The CTGF level was increased by using 0.25 mg/ml bevacizumab but decreased at the 0.8 mg/ml concentration of bevacizumab. Treatment with anti-CTGF antibody decreased MMP-2 expression whereas combined treatment with bevacizumab and anti-CTGF resulted in decreased expression of MMP-2, TIMP-1, cathepsin D, VEGFA, CTGF, and α-SMA in the treated cultures. Treatment of RPE cells with the combination of bevacizumab and anti-CTGF could effectively suppress the proangiogenic and profibrotic activity of RPE cells.

MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

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Hiura, Kazuya; Shiraishi, Akiko; Suzuki, Chinami; Takamura, Kei; Yamamoto, Makoto; Komori, Hitoshi; Watanabe, Yasuhiro; Iwaki-Egawa, Sachiko

2015-01-01

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

Refractive and Biometric Outcomes in Patients with Retinopathy of Prematurity Treated with Intravitreal Injection of Ranibizumab as Compared with Bevacizumab: A Clinical Study of Correction at Three Years of Age.

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Chen, Yen-Chih; Chen, San-Ni; Yang, Benjamin Chi-Lan; Lee, Kun-Hsien; Chuang, Chih-Chun; Cheng, Chieh-Yin

2018-01-01

To compare refractive and biometric outcomes in patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of ranibizumab (IVR) versus bevacizumab (IVB), at a corrected age of 3 years. A retrospective case series compared cycloplegic refractive statuses and biometric statuses in patients who received either IVR or IVB for type 1 ROP, from April 2011 to April 2014. A total of 62 eyes (33 patients) with type 1 ROP were evaluated (26 eyes in 13 IVR patients and 36 eyes in 20 IVB patients). There were no differences in birth statuses including gestational age and birth body weight between the two groups. The prevalence of refractive error greater than 1 D was higher in the IVB group ( p = 0.03), and there was a higher prevalence of high myopia (biometric finding showed that IVB patients had shallower anterior chamber depth ( p = 0.01). Both IVR and IVB showed low refractive errors, even followed at the corrected age of 3 years. No difference was noted between the two groups in refractive statuses. However, IVB was associated with shallower anterior chamber and higher prevalence of refractive error at the corrected age of 3 years. This trial is registered with NCT03334513.

Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography

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Reza Golestani

2013-06-01

Full Text Available Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.

Cetuximab reduces the accumulation of radiolabeled bevacizumab in cancer xenografts without altering VEGF expression

NARCIS (Netherlands)

Heskamp, S.; Boerman, O.C.; Molkenboer-Kuenen, J.D.M.; Sweep, F.C.; Geurts-Moespot, A.; Engelhardt, M.S.; Graaf, W.T.A. van der; Oyen, W.J.G.; Laarhoven, H.W.M. van

2014-01-01

Introduction: Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the

Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme

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Shields, Lisa BE; Kadner, Robert; Vitaz, Todd W; Spalding, Aaron C

2013-01-01

We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m 2 ) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m 2 × 5 days) and BEV were delivered monthly until progression or 12 months total. With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ

Nanoparticles in Porous Microparticles Prepared by Supercritical Infusion and Pressure Quench Technology for Sustained Delivery of Bevacizumab

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K.Yandrapu, Sarath; Upadhyay, Arun K.; Petrash, J. Mark; Kompella, Uday B.

2014-01-01

Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9 fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Flour 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. PMID:24131101

Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab.

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Yandrapu, Sarath K; Upadhyay, Arun K; Petrash, J Mark; Kompella, Uday B

2013-12-02

Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9-fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Fluor 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases.

Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

NARCIS (Netherlands)

Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

2014-01-01

Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

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Yan Lu

2014-02-01

Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

OUTCOMES AFTER LASER VERSUS COMBINED LASER AND BEVACIZUMAB TREATMENT FOR TYPE 1 RETINOPATHY OF PREMATURITY IN ZONE I.

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Yoon, Je Moon; Shin, Dong Hoon; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Chang, Yun Sil; Park, Won Soon

2017-01-01

To investigate the anatomical and refractive outcomes in patients with Type 1 retinopathy of prematurity in Zone I. The medical records of 101 eyes of 51 consecutive infants with Type 1 retinopathy of prematurity in Zone I were analyzed. Infants were treated by conventional laser photocoagulation (Group I), combined intravitreal bevacizumab injection and Zone I sparing laser (Group II), or intravitreal bevacizumab with deferred laser treatment (Group III). The proportion of unfavorable anatomical outcomes including retinal fold, disc dragging, retrolental tissue obscuring the view of the posterior pole, retinal detachment, and early refractive errors were compared among the three groups. The mean gestational age at birth and the birth weight of all 51 infants were 24.3 ± 1.1 weeks and 646 ± 143 g, respectively. In Group I, an unfavorable anatomical outcome was observed in 10 of 44 eyes (22.7%). In contrast, in Groups II and III, all eyes showed favorable anatomical outcomes without reactivation or retreatment. The refractive error was less myopic in Group III than in Groups I and II (spherical equivalent of -4.62 ± 4.00 D in Group I, -5.53 ± 2.21 D in Group II, and -1.40 ± 2.19 D in Group III; P prematurity in Zone I, intravitreal bevacizumab with concomitant or deferred laser therapy yielded a better anatomical outcome than conventional laser therapy alone. Moreover, intravitreal bevacizumab with deferred laser treatment resulted in less myopic refractive error.

Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients.

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Pathak, Surajit; S, Sushmitha; Banerjee, Antara; Marotta, Francesco; Gopinath, Madhumala; Murugesan, Ramachandran; Zhang, Hong; B, Bhavani; Girigoswami, Agnishwar; Sollano, Jose; Sun, Xiao-Feng

2018-01-26

Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS . Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS , validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

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Rony Carlos Preti

2012-02-01

Full Text Available PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001 but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm reduced significantly one month (322 ± 127 µm, P=0.0001 and three months (439 ± 179 µm, P=0.01 after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

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Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

2017-02-28

Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

Efficient production of a bioactive Bevacizumab monoclonal antibody using the 2A self-cleavage peptide in transgenic rice callus

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Lei Chen

2016-08-01

Full Text Available Bevacizumab, a humanized monoclonal antibody (mAb targeting to the vascular endothelial growth factor (VEGF, has been widely used in clinical practice for the treatment of multiple cancers. Bevacizumab was mostly produced by the mammalian cell expression system. We here reported the first plant-derived Bevacizumab by using transgenic rice callus as an alternative gene expression system. Codon-optimized Bevacizumab light chain (BLC and heavy chain (BHC genes were designed, synthesized as a polyprotein with a 2A self-cleavage linker peptide from the Foot-and-mouth disease virus (FMDV, cloned into a plant binary vector under a constitutive maize ubiquitin promoter, and transformed into rice nuclear genome through Agrobacterium-mediated transformation. Southern blot and western blot analyses confirmed the integration and expression of BLC and BHC genes in transgenic rice callus. Enzyme linked immunosorbent assay (ELISA analysis indicated that the rice-derived Bevacizumab mAb was biologically active and the recombinant mAb was expressed at high levels (160.7-242.8 mg kg-1FW in transgenic rice callus. The mAb was purified by using protein A affinity chromatography and the purified antibody was tested for its binding affinity with its target hVEGF antigen by ELISA. Rice callus produced Bevacizumab and a commercial Bevacizumab (Avastin were shown to have similar binding affinity to hVEGF. These results indicated that rice callus produced Bevacizumab could have similar biological activity and might potentially be used as a cost-effective biosimilar molecule in future cancer treatment.

Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

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Grimelda Yuriana Sánchez-Castro

2008-10-01

Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer

NARCIS (Netherlands)

Tol, Jolien; Koopman, Miriam; Cats, Annemieke; Rodenburg, Cees J.; Creemers, Geert J. M.; Schrama, Jolanda G.; Erdkamp, Frans L. G.; Vos, Allert H.; van Groeningen, Cees J.; Sinnige, Harm A. M.; Richel, Dirk J.; Voest, Emile E.; Dijkstra, Jeroen R.; Vink-Börger, Marianne E.; Antonini, Ninja F.; Mol, Linda; van Krieken, Johan H. J. M.; Dalesio, Otilia; Punt, Cornelis J. A.

2009-01-01

Background Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor ( VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor ( EGFR) antibody cetuximab

Umbilical cord blood-derived natural killer cells combined with Bevacizumab for colorectal cancer treatment.

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Xu, Chen; Liu, Dongning; Chen, Zhixin; Zhuo, Fan; Sun, Huankui; Hu, Jiaping; Li, Taiyuan

2018-06-19

Colorectal cancer (CRC) is among cancers with highest incidence globally and currently ranks fourth as the leading cause of cancer-related deaths worldwide. It remains an urgent need for novel strategies in the management of patients with advanced CRC. Adoptive transfer of allogeneic natural killer (NK) cells represent an attractive option in the treatment of patients with CRC. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound IL-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of IFN-γ, TNF-α, GM-CSF and CCL3 compared with IL-2 stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. More NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Combination of bevacizumab can increase extravasation of adoptively transferred NK cells into the LoVo tumors and improve the therapeutic activity of eUCB-NK cells. These results justified clinical translation of this UCB-derived NK cell-based therapeutics, either used alone or combined with bevacizumab, as a novel treatment option for patients with CRC.

Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary to iris metastasis of breast carcinoma

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Stephanie Vale

2018-03-01

Conclusions & importance: A single intravitreal bevacizumab injection may be sufficient to achieve palliative control of neovascular glaucoma secondary to iris breast cancer metastasis. To our knowledge, this is the first case report in which a single intravitreal bevacizumab injection was used for the effective management of this condition.

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

NARCIS (Netherlands)

Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

2009-01-01

Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma

International Nuclear Information System (INIS)

Lou, Emil; Peters, Katherine B; Sumrall, Ashley L; Desjardins, Annick; Reardon, David A; Lipp, Eric S; Herndon, James E II; Coan, April; Bailey, Leighann; Turner, Scott; Friedman, Henry S; Vredenburgh, James J

2013-01-01

Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6–10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m 2 on days 1–5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 nonhematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials

Perfluorocarbon in vitreoretinal surgery and preoperative bevacizumab in diabetic tractional retinal detachment

Institute of Scientific and Technical Information of China (English)

J; Fernando; Arevalo; Martin; A; Serrano; Juan; D; Arias

2014-01-01

AIM: To describe the en bloc perfluorodissection(EBPD) technique and to demonstrate the applicabilityof using preoperative intravitreal bevacizumab duringsmall-gauge vitreoretinal surgery(23-gauge transconjunctival sutureless vitrectomy) in eyes with advancedproliferative diabetic retinopathy(PDR) with tractionalretinal detachment(TRD).METHODS: This is a prospective, interventional caseseries. Participants included 114(eyes) with advancedproliferative diabetic retinopathy and TRD. EBPD wasperformed in 114 eyes(consecutive patients) during23-gauge vitrectomy with the utilization of preoperativebevacizumab(1.25 mg/-0.05 mL). Patients mean age was 45 years(range, 21-85 years). Surgical time had a mean of 55 min(Range, 25-85 min). Mean follow up of this group of patients was 24 mo(range, 12-32 mo). Main outcome measures included best-corrected visual acuity(BCVA), retinal reattachment, and complications.RESULTS: Anatomic success occurred in 100%(114/-114) of eyes. Significant visual improvement [≥ 2 Early Treatment Diabetic Retinopathy Study(ETDRS) lines] was obtained in 69.2%(79/-114), in 26 eyes(22.8%) BCVA remained stable, and in 8 eyes(7%) BCVA decreased(≥ 2 ETDRS lines). Final BCVA was 20/-50 or better in 24% of eyes, between 20/-60 and 20/-400 in 46% of eyes, and worse than 20/-400 in 30% of eyes. Complications included cataract in 32(28%) eyes, iatrogenic retinal breaks in 9(7.8%) eyes, vitreous hemorrhage requiring another procedure in 7(6.1%) eyes, and phthisis bulbi in 1(0.9%) eye.CONCLUSION: This study demonstrates the usefulne-ss of using preoperative intravitreal bevacizumab and EBPD during smallgauge vitreoretinal surgery in eyes with TRD in PDR.

Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

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Toyama Yoichi

2012-06-01

Full Text Available Abstract A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.

Durable clinical activity of single-agent bevacizumab in a nonagenarian patient with metastatic alveolar soft part sarcoma.

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Mir, Olivier; Boudou-Rouquette, Pascaline; Larousserie, Frédérique; Blanchet, Benoit; Babinet, Antoine; Anract, Philippe; Goldwasser, François

2012-08-01

Alveolar soft part sarcoma is a rare malignancy usually considered resistant to conventional chemotherapy, but recent data suggest that the multikinase inhibitors sunitinib and cediranib could be active in this setting. A 90-year-old lady with alveolar soft part sarcoma of the leg and lung metastases was started on sunitinib 37.5 mg daily. The treatment was poorly tolerated with grade 3 hypertension and grade 3 thrombocytopenia, which persisted after dose reduction to 25 mg daily. The patient was subsequently started on bevacizumab 10 mg/kg every 2 weeks, resulting in a marked improvement in pain and a partial response on lung metastases for 16 months and ongoing. Agents targeting the vascular endothelial growth factor-signalling pathway seem to exert clinically relevant and prolonged activity against alveolar soft part sarcoma and deserve further evaluation in the treatment of this rare soft tissue sarcoma.

Efficacy of Bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma

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Qian Wang

2018-03-01

Full Text Available AIM:To investigate the efficacy of Bevacizumab intravitreal injection combined with EX-PRESS in the treatment of refractory glaucoma. METHODS: The research objects were 150 cases(150 eyesof patients with refractory glaucoma from June 2014 to December 2016 in our hospital. All patients were treated with EX-PRESS glaucoma drainage device implantation, and their medicine data were analyzed retrospectively. Totally 70 cases(70 eyeswere treated with EX-PRESS only were set as the control group; 80 cases(80 eyesreceived bevacizumab intravitreal injection on the basis of the treatment of the control group were set as the observation group. The successful rate of operation was evaluated, the intraocular pressure was measured before operation and at 7d, 1, 3, 6mo after treatment by non-contact conometer, followed by record of the visual acuity and complications before and after 6mo of treatment. RESULTS: The observation group's total surgical success rate was 72.5%, which was sharply higher than that of the control group(58.6%; while the partial success rate was 17.5%, which was significantly lower than that of the control group(30.0%, with statistical significance(χ2=5.453, P=0.028; χ2=4.213, P=0.047. Two groups' surgical failure rate had no distinct difference(χ2=0.000, P=1.000. There was no significant difference in visual acuity of the two groups before and after operation(P>0.05. There was no significant difference in intraocular pressure between the two groups(Fgroups=982.27, PFtime=941.88, PPP>0.05. The observation group's low intraocular pressure, anterior chamber bleeding and shallow anterior chamber incidence were significantly lower than those of the control group, there was statistical meaning(PCONCLUSION: Intravitreal injection of bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma can improve the complete success rate, as well as perform effective control on complications such as short-term intraocular pressure

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5.

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Jalali, Subhadra; Balakrishnan, Divya; Zeynalova, Zarifa; Padhi, Tapas Ranjan; Rani, Padmaja Kumari

2013-07-01

To report serious adverse events and long-term outcomes of initial experience with intraocular bevacizumab in retinopathy of prematurity (ROP). Consecutive vascularly active ROP cases treated with bevacizumab, in addition to laser and surgery, were analysed retrospectively from a prospective computerised ROP database. Primary efficacy outcome was regression of new vessels. Secondary outcomes included the anatomic and visual status. Serious systemic and ocular adverse events were documented. 24 ROP eyes in 13 babies, received single intraocular bevacizumab for severe stage 3 plus after failed laser (seven eyes), stage 4A plus (eight eyes), and stage 4B/5 plus (nine eyes). Drug was injected intravitreally in 23 eyes and intracamerally in one eye. New vessels regressed in all eyes. Vision salvage in 14 of 24 eyes and no serious neurodevelopmental abnormalities were noted up to 60 months (mean 30.7 months) follow-up. Complications included macular hole and retinal breaks causing rhegmatogenous retinal detachment (one eye); bilateral, progressive vascular attenuation, perivascular exudation and optic atrophy in one baby, and progression of detachment bilaterally to stage 5 in one baby with missed follow-up. One baby who received intracameral injection developed hepatic dysfunction. One eye of this baby also showed a large choroidal rupture. Though intraocular bevacizumab, along with laser and surgery salvaged vision in many otherwise progressive cases of ROP, vigilance and reporting of serious adverse events is essential for future rationalised use of the drug. We report one systemic and four ocular adverse events that require consideration in future use of the drug.

Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer

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Larsen, Finn Ole; Markussen, Alice; Diness, Laura V

2018-01-01

, there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced...

Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

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Stinchcombe, Thomas E

2007-09-01

Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

Is more better than less? Caveats from bevacizumab and cetuximab combination in colorectal cancer

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Camillo Porta

2011-12-01

Full Text Available In the past few years, impressing improvements have been made in the treatment of advanced colorectal cancer. Following decades of modest achievements, in which it was just a matter of dose and schedule for 5-FU and leucovorin—the only treatment then available—first, the development of irinotecan and oxaliplatin, and then the use of the two biologicals, bevacizumab and cetuximab, have dramatically improved the life expectancy of our colorectal cancer patients...

Synthesis, radiolabeling and quality control of {sup 111}In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

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Khorami-Moghadam, A.; Jalilian, A.R.; Yavari, K.; Alirezapour, B.; Mazidi, M.; Mirzaii, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

2013-11-01

In this study, bevacizumab was successively labeled with {sup 111}In-InCl{sub 3} after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of {sup 111}In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). {sup 111}In-DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology. (orig.)

Effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells

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Jun JH

2016-06-01

Full Text Available Jong Hwa Jun,1 Wern-Joo Sohn,2 Youngkyun Lee,2 Jae-Young Kim21Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung University, 2Department of Oral Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South KoreaAbstract: The molecular and cellular effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells (LECs were examined using both an immortalized human lens epithelial cell line and a porcine capsular bag model. After treatment with various concentrations of bevacizumab, cell viability and proliferation patterns were evaluated using the water-soluble tetrazolium salt assay and 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay, respectively. The scratch assay and Western blot analysis were employed to validate the cell migration pattern and altered expression levels of signaling molecules related to the epithelial–mesenchymal transition (EMT. Application of bevacizumab induced a range of altered cellular events in a concentration-dependent manner. A 0.1–2 mg/mL concentration demonstrated dose-dependent increase in proliferation and viability of LECs. However, 4 mg/mL decreased cell proliferation and viability. Cell migrations displayed dose-dependent retardation from 0.1 mg/mL bevacizumab treatment. Transforming growth factor-β2 expression was markedly increased in a dose-dependent manner, and α-smooth muscle actin, matrix metalloproteinase-9, and vimentin expression levels showed dose-dependent changes in a B3 cell line. Microscopic observation of porcine capsular bag revealed changes in cellular morphology and a decline in cell density compared to the control after 2 mg/mL treatment. The central aspect of posterior capsule showed delayed confluence, and the factors related to EMT revealed similar expression patterns to those identified in the cell line. Based on these results, bevacizumab modulates the proliferation

Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation.

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Miraftabi, Arezoo; Nilforushan, Naveed

2016-01-01

To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery.

In vitro induction of protein complexes between bevacizumab, VEGF-A¹⁶⁵ and heparin: explanation for deposits observed on endothelial veins in monkey eyes.

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Julien, Sylvie; Biesemeier, Antje; Schraermeyer, Ulrich

2013-04-01

By investigating the effects of intravitreal bevacizumab on retinal vessels of monkeys, we found that bevacizumab accumulated locally at high concentration within individual blood vessels. It formed electron-dense fibrous deposits between endothelial cells and erythrocytes or granulocytes inducing retinal vein thrombosis. To better characterise the observed deposits, we investigated in vitro whether these deposits result from a complex between bevacizumab, vascular endothelial growth factor (VEGF)-A(165) and heparin. Cynomolgus monkeys were intravitreally injected with 1.25 mg bevacizumab. The eyes were enucleated between 1 and 14 days after injection and investigated by electron microscopy and immunohistochemistry. Human umbilical vein endothelial cells (HUVEC) were incubated with bevacizumab, VEGF-A(165) and heparin at different concentrations. Treatments with ranibizumab served as control. Bevacizumab and ranibizumab were detected immunohistochemically using Cy-3 or immunogold labelled antibodies. Treated animals showed bevacizumab locally at high concentration within retinal blood vessels. Electron-dense deposits inside retinal vessels and between erythrocytes were detected in three out of four treated monkeys. In vitro, many globular aggregates heavily stained with anti-human IgG were only observed with equimolar amounts (240 nM) of bevacizumab and VEGF-A(165) and 0.2 U/ml heparin and not after ranibizumab treatment. The immunogold labelling specifically localised ultrastructurally the complexes formed between bevacizumab, VEGF-A(165) and heparin at the surfaces of HUVEC cells. Heparin promotes bevacizumab immune complex deposition on to endothelial cells. Our in vitro results could explain the presence of deposits observed on endothelial veins in monkey eyes intravitreally injected with bevacizumab.

A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

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Bunce Catey

2008-10-01

Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

Wound dehiscence and device migration after subconjunctival bevacizumab injection with Ahmed glaucoma valve implantation

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Arezoo Miraftabi; Naveed Nilforushan

2016-01-01

Purpose: To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. Case Report: A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposur...

Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

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Qingqing PAN

2011-07-01

Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

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Lai XX

2016-04-01

Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

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Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

2015-01-01

Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m 2 . Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity

Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

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Wells, John A; Glassman, Adam R; Ayala, Allison R; Jampol, Lee M; Bressler, Neil M; Bressler, Susan B; Brucker, Alexander J; Ferris, Frederick L; Hampton, G Robert; Jhaveri, Chirag; Melia, Michele; Beck, Roy W

2016-06-01

To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Randomized clinical trial. Six hundred sixty participants with visual acuity (VA) impairment from DME. Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Change in VA, adverse events, and retreatment frequency. Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials. Copyright © 2016 American Academy of Ophthalmology. All rights

Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up

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Eleni Loukianou

2010-05-01

Full Text Available Eleni Loukianou, Dimitrios Brouzas, Eleni Georgopoulou, Chrysanthi Koutsandrea, Michael ApostolopoulosEye Department, University of Athens, Athens, GreecePurpose: To evaluate the safety and efficacy of intravitreal injections of bevacizumab (Avastin® as a treatment option for radiation maculopathy secondary to proton beam radiotherapy for choroidal melanoma.Case: A 61-year-old woman presented with a gradual decrease in left eye visual acuity (VA 29 months after proton beam radiotherapy for choroidal melanoma. On presentation, her best-corrected VA (BCVA was 2/10 in the left eye and the intraocular pressure was 15 mmHg. Fundoscopy revealed cystoid macular edema, intraretinal hemorrhages, epiretinal membrane in the posterior pole, and residual tumor scar with exudative retinal detachment and hard exudates in the periphery of the superotemporal quadrant. A treatment with intravitreal injections of bevacizumab (Avastin® was recommended. The injections were performed on a six-weekly basis.Results: The central retinal thickness prior to the treatment was 458 μm. After the first intravitreal injection of bevacizumab, the retinal thickness at the centre of the fovea was reduced to 322 μm. After the third injection, the central retinal thickness was 359 μm and 18 months after presentation, it reduced to 334 μm. The BCVA increased to 3/10 after the intravitreal injections of bevacizumab and remained stable during the follow-up period. The intraocular pressure was within normal range during the follow-up period.Conclusion: Bevacizumab should be regarded as a treatment option for macular edema due to proton beam radiotherapy for choroidal melanoma. By reducing the central retinal thickness, intravitreal bevacizumab can improve VA or ameliorate further decline caused by radiation maculopathy.Keywords: bevacizumab (Avastin®, choroidal melanoma, macular edema, radiation retinopathy

Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

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Lang, I; Inbar, M J; Kahán, Z; Greil, R; Beslija, S; Stemmer, S M; Kaufman, B; Zvirbule, Z; Steger, G G; Messinger, D; Brodowicz, T; Zielinski, C

2012-11-01

We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA trial.

Science.gov (United States)

Llombart-Cussac, Antonio; Pivot, Xavier; Biganzoli, Laura; Cortes-Funes, Hernan; Pritchard, Kathleen I; Pierga, Jean-Yves; Smith, Ian; Thomssen, Christoph; Srock, Stefanie; Sampayo, Miguel; Cortes, Javier

2014-10-01

Evidence-based definitions of 'poor-prognosis' or 'aggressive' advanced breast cancer are lacking. We developed a prognostic factor index using data from 2203 patients treated with first-line chemotherapy plus bevacizumab for HER2-negative advanced breast cancer. The risk factors most closely associated with worse OS were: disease-free interval ≤24 months; liver metastases or ≥3 involved organ sites; prior anthracycline and/or taxane therapy; triple-negative breast cancer (TNBC); and performance status 2 or prior analgesic/corticosteroid treatment. Risk of death was increased threefold in patients with ≥3 versus ≤1 risk factors (hazard ratio 3.0 [95% CI 2.6-3.4; p < 0.001]; median 16.0 vs 38.8 months, respectively). This prognostic index may enable identification of patients with a poorer prognosis in whom more intensive systemic regimens may be appropriate. The index may also be considered in designing new trials, although it requires validation in other datasets before extrapolation to non-bevacizumab-containing therapy. ClinicalTrials.gov identifier: NCT00448591. Copyright © 2014 Elsevier Ltd. All rights reserved.

Macular Hole Progression after Intravitreal Bevacizumab for Hemicentral Retinal Vein Occlusion

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Manish Nagpal

2011-01-01

Full Text Available Macular edema secondary to retinal vein occlusion is commonly being treated with off-label intravitreal bevacizumab with good outcomes. A significant reduction in macular edema and improvement in visual acuity is seen following such a treatment with no serious adverse effects. In the reported case, a full-thickness macular hole was noticed one month after intravitreal bevacizumab for macular edema secondary to hemicentral retinal vein occlusion. On a detailed review of the pre- and postoptical coherence tomography scans, it was realized that there was a preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema at the fovea and the macular hole had progressed following the injection.

Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

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Hisanori Imai

2011-09-01

Full Text Available Purpose: To report a case of proliferative diabetic retinopathy (PDR showing transient macular edema (ME and deteriorated retinal function after intravitreal bevacizumab injection (IVB. Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+ in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

Real-world and trial-based cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer patients: a study of the Southeast Netherlands Breast Cancer Consortium.

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van Kampen, R J W; Ramaekers, B L T; Lobbezoo, D J A; de Boer, M; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G; Peters, N A J B; Tjan-Heijnen, V C G; Joore, M A

2017-07-01

The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial. A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted. In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained. According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase 1 dose-escalation study of the antiplacental growth factor monoclonal antibody RO5323441 combined with bevacizumab in patients with recurrent glioblastoma

DEFF Research Database (Denmark)

Lassen, Ulrik; Chinot, Olivier L; McBain, Catherine

2015-01-01

BACKGROUND: We conducted a phase 1 dose-escalation study of RO5323441, a novel antiplacental growth factor (PlGF) monoclonal antibody, to establish the recommended dose for use with bevacizumab and to investigate the pharmacokinetics, pharmacodynamics, safety/tolerability, and preliminary clinica...

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

Science.gov (United States)

Wiley, Henry E; Thompson, Darby J S; Bailey, Clare; Chew, Emily Y; Cukras, Catherine A; Jaffe, Glenn J; Lee, Richard W J; Loken, Erin K; Meyerle, Catherine B; Wong, Wai; Ferris, Frederick L

2016-04-01

To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab

Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial.

Science.gov (United States)

Cremolini, Chiara; Antoniotti, Carlotta; Lonardi, Sara; Aprile, Giuseppe; Bergamo, Francesca; Masi, Gianluca; Grande, Roberta; Tonini, Giuseppe; Mescoli, Claudia; Cardellino, Giovanni Gerardo; Coltelli, Luigi; Salvatore, Lisa; Corsi, Domenico Cristiano; Lupi, Cristiana; Gemma, Donatello; Ronzoni, Monica; Dell'Aquila, Emanuela; Marmorino, Federica; Di Fabio, Francesca; Mancini, Maria Laura; Marcucci, Lorenzo; Fontanini, Gabriella; Zagonel, Vittorina; Boni, Luca; Falcone, Alfredo

2018-04-01

The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC. In a prospective, noncomparative, open-label, multicenter, randomized phase 2 trial, patients aged 18 to 75 years with unresectable, previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type) mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were screened and 143 were randomized to 2 treatment arms to receive as a first-line induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or bevacizumab (arm B) until disease progression. Primary analyses were conducted in a modified intention-to-treat population. mFOLFOXIRI plus cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with cetuximab or bevacizumab until disease progression. The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events. Of 143 patients randomized, 116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34 [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of 44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall response rate was 71.6% (95% CI, 62.4%-79.5%). Main grade 3/4 adverse events were neutropenia (occurring in 36

Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

International Nuclear Information System (INIS)

Cabrera, Alvin R.; Cuneo, Kyle C.; Desjardins, Annick; Sampson, John H.; McSherry, Frances; Herndon, James E.; Peters, Katherine B.; Allen, Karen; Hoang, Jenny K.; Chang, Zheng; Craciunescu, Oana; Vredenburgh, James J.; Friedman, Henry S.; Kirkpatrick, John P.

2013-01-01

Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach

Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

Science.gov (United States)

Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

2018-04-24

Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme

DEFF Research Database (Denmark)

Hofland, Kenneth F; Hansen, Steinbjørn; Sorensen, Morten

2014-01-01

BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated...... from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS....

A systematic review of bevacizumab efficacy in breast cancer

DEFF Research Database (Denmark)

Kümler, Iben; Christiansen, Ole Grummedal; Nielsen, Dorte Lisbet

2014-01-01

demonstrated an OS benefit. In the neoadjuvant setting 23 phase II and III trials were identified. All studies found increased pCR/tpCR but no benefit in terms of OS could be demonstrated. The only study conducted in the adjuvant setting failed to show any survival benefit of bevacizumab. CONCLUSION: Despite...

Neo-Vascular Glaucoma: Etiology and Outcome of Treatment in Lagos

African Journals Online (AJOL)

tulyasys

therapy of ocular medications, intraocular bevacizumab injections and retinal laser photocoagulation treatments showed an average IOP reduction of 19 mmHg [Table 5]. However, the remaining 11 patients who came for follow-up but did not receive either intravitreal bevacizumab or PRP showed different paern of IOP.

Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

Science.gov (United States)

Willett, Christopher G; Boucher, Yves; di Tomaso, Emmanuelle; Duda, Dan G; Munn, Lance L; Tong, Ricky T; Chung, Daniel C; Sahani, Dushyant V; Kalva, Sanjeeva P; Kozin, Sergey V; Mino, Mari; Cohen, Kenneth S; Scadden, David T; Hartford, Alan C; Fischman, Alan J; Clark, Jeffrey W; Ryan, David P; Zhu, Andrew X; Blaszkowsky, Lawrence S; Chen, Helen X; Shellito, Paul C; Lauwers, Gregory Y; Jain, Rakesh K

2009-01-01

The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. PMID:14745444

Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

DEFF Research Database (Denmark)

Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

2010-01-01

, 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 cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy....

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer

Science.gov (United States)

Kuesters, Geoffrey M.

Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy

Directory of Open Access Journals (Sweden)

Paola Ulivi

2017-06-01

Full Text Available There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided in patients with metastatic colorectal cancer (mCRC. We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa”, randomized to receive first-line chemotherapy (CT or CT plus bevacizumab (CT + B. RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, cyclooxygenase-2 (COX2, ephrin type-B receptor 4 (EPHB4, hypoxia-inducible factor 1-alpha (HIF-1α, lactate dehydrogenase (LDH, and high-sensitivity C reactive protein (hs-CRP; and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017. Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

Science.gov (United States)

MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

2014-01-01

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

DEFF Research Database (Denmark)

Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

2010-01-01

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...... 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....

Is phenytoin contraindicated in patients receiving cranial irradiation?

Energy Technology Data Exchange (ETDEWEB)

Borg, M.F. [Royal Adelaide Hospital, SA (Australia); Probert, J.C. [Auckland Hospital, Auckland (New Zealand). Dept. of Radiation Oncology; Zwi, L.J. [Auckland Univ. (New Zealand). Dept. of Medicine and Surgery

1995-02-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs.

Is phenytoin contraindicated in patients receiving cranial irradiation?

International Nuclear Information System (INIS)

Borg, M.F.; Probert, J.C.; Zwi, L.J.

1995-01-01

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation. 21 refs., 2 tabs., 3 figs

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.