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Shunji Kusaka - One of the best experts on this subject based on the ideXlab platform.
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serum concentrations of Bevacizumab avastin and vascular endothelial growth factor in infants with retinopathy of prematurity
American Journal of Ophthalmology, 2012Co-Authors: Tatsuhiko Sato, Kazuko Wada, Hitomi Arahori, Noriyuki Kuno, Kenji Imoto, Chiharu Iwahashishima, Shunji KusakaAbstract:Purpose To determine the serum concentrations of Bevacizumab and vascular endothelial growth factor (VEGF) in infants with retinopathy of prematurity (ROP) who received intravitreal Bevacizumab; and to determine whether the changes in the serum concentration of Bevacizumab were significantly correlated with the serum concentration of VEGF after intravitreal Bevacizumab. Design Case series. Methods Eleven infants (4 girls and 7 boys) with ROP were studied. They received 0.25 mg or 0.5 mg of intravitreal Bevacizumab to either 1 eye (unilateral cases) or both eyes (bilateral cases) with vascularly active ROP. Serum samples were collected before and 1 day, 1 week, and 2 weeks after the intravitreal Bevacizumab. The serum concentrations of Bevacizumab and VEGF were measured by enzyme-linked immunosorbent assay, and the correlation in the serum levels between the 2 was determined. Results The serum concentration of Bevacizumab before and 1 day, 1week, and 2 weeks after a total of 0.5 mg of intravitreal Bevacizumab was 0 ng/mL, 195 ± 324 ng/mL, 946 ± 680 ng/mL, and 1214 ± 351 ng/mL, respectively. The serum Bevacizumab level before and 1 day and 1 week after a total 1.0 mg of intravitreal Bevacizumab was 0 ng/mL, 248 ± 174 ng/mL, and 548 ± 89 ng/mL, respectively. The serum concentration of VEGF before and 1 day, 1 week, and 2 weeks after a total of 0.5 mg intravitreal Bevacizumab was 1628 ± 929 pg/mL, 427 ± 140 pg/mL, 246 ± 110 pg/mL, and 269 ± 157 pg/mL, respectively. There was a significant negative correlation ( r = −0.575, P = .0125) between the serum concentration of Bevacizumab and VEGF when a total of 0.25 mg or 0.5 mg of Bevacizumab was injected. Conclusions These results indicate that Bevacizumab can escape from the eye into the systemic circulation and reduce the serum level of VEGF in infants with ROP. Continued extensive evaluations of infants are warranted for possible effects after intravitreal Bevacizumab in ROP patients.
Steve Brocchini - One of the best experts on this subject based on the ideXlab platform.
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Storage stability of Bevacizumab in polycarbonate and polypropylene syringes
Eye, 2015Co-Authors: Hamzeh Khalili, A Froome, G. Sharma, Peng T. Khaw, Steve BrocchiniAbstract:PurposeTo compare and examine the storage stability of compounded Bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and Bevacizumab stability has not been reported for this type of syringe.MethodsRepackaged Bevacizumab was obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with Bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of Bevacizumab in solution. VEGF binding and the active concentration of Bevacizumab was determined by surface plasmon resonance (SPR) using Biacore.ResultsSDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular weight species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared with Bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of Bevacizumab in the PC syringe after 6 months of storage was not significantly different to Bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of Bevacizumab in the PC syringe was comparable to Bevacizumab taken from a freshly opened vial.ConclusionNo significant difference over a 6-month period was observed in the quality of Bevacizumab repackaged into prefilled polycarbonate and polypropylene syringes when compared with Bevacizumab that is supplied from the vial.
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Storage stability of Bevacizumab in polycarbonate and polypropylene syringes.
Eye (London England), 2015Co-Authors: Hanieh Khalili, A Froome, G. Sharma, Peng T. Khaw, Steve BrocchiniAbstract:To compare and examine the storage stability of compounded Bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and Bevacizumab stability has not been reported for this type of syringe. Repackaged Bevacizumab was obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with Bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of Bevacizumab in solution. VEGF binding and the active concentration of Bevacizumab was determined by surface plasmon resonance (SPR) using Biacore. SDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular weight species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared with Bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of Bevacizumab in the PC syringe after 6 months of storage was not significantly different to Bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of Bevacizumab in the PC syringe was comparable to Bevacizumab taken from a freshly opened vial. No significant difference over a 6-month period was observed in the quality of Bevacizumab repackaged into prefilled polycarbonate and polypropylene syringes when compared with Bevacizumab that is supplied from the vial.
Daniele Generali - One of the best experts on this subject based on the ideXlab platform.
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Bevacizumab in small cell lung cancer
Translational cancer research, 2017Co-Authors: Giandomenico Roviello, Daniele GeneraliAbstract:Tiseo et al . published the clinical study evaluating the efficacy and the safety of Bevacizumab a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF), combined with cisplatin and etoposide in first line chemotherapy for patients with extensive-disease (ED) of small-cell lung cancer (SCLC) (1). This is a multicenter, open-label, randomized controlled phase III trial supported by the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)—Agenzia Italiana del Farmaco FARM6PMFJM. A total of 205 patients were randomly assigned receiving cisplatin and etoposide with or without Bevacizumab. The primary end point was the overall survival (OS). At a median follow-up of 34.9 months, the median OS was improved in the Bevacizumab arm (9.8 vs . 8.9 months; hazard ratio (HR) 0.78) with a 1-year survival rates of 37% and 25% respectively (HR 0.78; 95% CI: 0.58–1.06; P=0.113). In addition, the proportion of patients who reported an objective response was 58.4% for the “Bevacizumab arm” and 55.3% for the control arm. Among the 96 patients treated with chemotherapy and Bevacizumab, 41 patients (42%) continued Bevacizumab beyond the preplanned sixth cycles of treatment with a median of four cycles of Bevacizumab maintenance; the 65.8% of patients interrupted Bevacizumab cause of disease progression. A statistically significant effect on the OS in whose patients receiving the Bevacizumab-based maintenance was observed (HR 0.60; P=0.011) along with a well tolerance and as expected; only hypertension was the most frequent adverse event registered in the Bevacizumab arm (grade 3 or 4, 6.3% vs . 1.0%; P=0.057).
Kazuhiko Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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randomized phase ii study of first line carboplatin paclitaxel with or without Bevacizumab in japanese patients with advanced non squamous non small cell lung cancer
Lung Cancer, 2012Co-Authors: Seiji Niho, Hideo Kunitoh, Hiroshi Nokihara, Takeshi Horai, Yukito Ichinose, Toyoaki Hida, Nobuyuki Yamamoto, Masaaki Kawahara, Tetsu Shinkai, Kazuhiko NakagawaAbstract:PURPOSE: This multicenter, randomized, open-label, phase II study (JO19907) compared the efficacy and safety of first-line carboplatin-paclitaxel (CP) alone with Bevacizumab-CP in Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Chemonaive patients with stage IIIB, IV or recurrent non-squamous NSCLC were eligible for participation. Patients were randomly assigned in a 2:1 ratio to receive Bevacizumab-CP or CP alone. Chemotherapy was repeated for up to 6 cycles or until disease progression or unacceptable toxicity. Bevacizumab recipients who completed ≥3 cycles of chemotherapy could continue Bevacizumab as monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: After confirming the tolerability of Bevacizumab-CP in a small number of patients, 180 patients were recruited, of whom 121 were assigned to Bevacizumab-CP and 59 to CP alone. Hazard ratio (HR) for PFS was 0.61 with Bevacizumab-CP versus CP alone (p=0.0090; median 6.9 versus 5.9 months). Objective response rate was significantly higher with Bevacizumab-CP than with CP alone (60.7% versus 31.0%; p=0.0013). Median overall survival was >22 months in both treatment groups (HR 0.99; p=0.9526). No new safety signals were detected. CONCLUSION: Study JO19907 met its primary endpoint, demonstrating that the addition of Bevacizumab to first-line CP significantly improves PFS in Japanese patients with advanced non-squamous NSCLC. This prolonged PFS by Bevacizumab did not translate into OS benefit with the extremely longer underlying survival compared to historical data. No new safety signals were identified in this population. (Japan Pharmaceutical Information Center [JAPIC] registration number: CTI-060338).
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Perirenal hematoma associated with Bevacizumab treatment
Investigational new drugs, 2010Co-Authors: Hidetoshi Hayashi, Isamu Okamoto, Kazuhiko NakagawaAbstract:We now describe the first example of a patient who developed perirenal hematoma during the course of Bevacizumab-containing chemotherapy. A 59-years-old woman with metastatic rectal cancer treated with Bevacizumab, who developed low back pain after 11 cycles of chemotherapy. CT-scan was consistent with perirenal hematoma and discontinuation of Bevacizumab resulted in symptomatic improvement. Nontraumatic perirenal hematoma is a rare condition that can cause shock in severe cases. Given that several types of bleeding complication are known to be associated with Bevacizumab treatment, we concluded that Bevacizumab likely contributed to the perirenal hematoma in this case. Although the appropriate modification of Bevacizumab treatment in the setting of perirenal hematoma is still unclear, physicians should be aware of this potential Bevacizumab-associated bleeding complication.
Bradley J Monk - One of the best experts on this subject based on the ideXlab platform.
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incorporation of Bevacizumab in the primary treatment of ovarian cancer
The New England Journal of Medicine, 2011Co-Authors: Robert A Burger, Mark F Brady, Michael A Bookman, Gini F Fleming, Bradley J Monk, Helen Q Huang, Robert S Mannel, Howard D Homesley, Jeffrey M Fowler, Benjamin E GreerAbstract:METHODS In our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks’ duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; Bevacizumab-initiation treatment was che motherapy with Bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with Bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival. RESULTS Overall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the Bevacizumab-initiation group, and 14.1 in the Bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P = 0.16) with Bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with Bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the Bevacizumab-initiation group (16.5%) and the Bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the Bevacizumab-initiation group, and the Bevacizumab-throughout group, respectively. CONCLUSIONS The use of Bevacizumab during and up to 10 months after carboplatin and pacli taxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. (Funded by the National Cancer Institute and Genentech; ClinicalTrials.gov number, NCT00262847.)
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Bevacizumab toxicities and their management in ovarian cancer
Gynecologic oncology, 2010Co-Authors: Leslie M. Randall, Bradley J MonkAbstract:Abstract Objectives The purpose of this review is to discuss the side effect profile of Bevacizumab, to discuss proposed mechanisms of these toxicities, and to provide suggestions for management of adverse events. Methods A search of MEDLINE and ASCO and SGO abstract databases of articles published between January 1970 and August 2009 addressing the toxicity of Bevacizumab in solid tumors was conducted. Reporting was limited to best available evidence including any available phase III studies and ovarian cancer phase II studies. Original publications addressing underlying mechanisms of Bevacizumab toxicities were included. Results Extensive experience with Bevacizumab has proven the agent to be generally well tolerated, with an adverse event profile distinct from traditional cytotoxic chemotherapy and likely peculiar to its novel mechanism of action. The most common Bevacizumab-attributable adverse event, hypertension, can be medically-managed, but more serious adverse events such as bowel perforation require drug discontinuation. Conclusions Current best evidence supports the use of Bevacizumab in selected patients, and safe administration of Bevacizumab requires an understanding of the management of adverse events attributable to its use.
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Bevacizumab in the treatment of ovarian cancer
Expert review of anticancer therapy, 2007Co-Authors: Ernest S. Han, Bradley J MonkAbstract:Current treatment for epithelial ovarian cancer involves a combination of surgery and chemotherapy with platinum- and taxane-based chemotherapy. With the recent approval of the anti-VEGF antibody Bevacizumab by several regulatory bodies in colorectal and non-small-cell lung cancers, interest has developed regarding the potential role of Bevacizumab therapy in ovarian cancer. Several case series and Phase II studies indicate that in ovarian cancer Bevacizumab is active as a single agent or in combination with other drugs. Currently, ongoing Phase III trials are testing Bevacizumab in front-line adjuvant therapy with carboplatin and paclitaxel. Bevacizumab has been generally well tolerated in ovarian cancer patients, but recent reports on increased risk of gastrointestinal perforations have gained attention. Bevacizumab offers a novel therapeutic modality in the treatment of epithelial ovarian cancers.
