Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

Eskander, Ramez N.; Tewari, Krishnansu S.

doi:10.1016/j.ygyno.2013.11.029

Cited by 96 publications

(57 citation statements)

References 65 publications

(77 reference statements)

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“…6 Attempts have been made to treat ovarian cancer using antiangiogenesis therapy, such as bevacizumab, in the clinical setting but side effects including thrombosis, proteinuria, and gastrointestinal perforation remain problematic. [7][8][9][10][11] Therefore, it is necessary to develop safer and more effective antiangiogenesis therapies for ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

Chen¹,

Wang

Liu

et al. 2015

IJN

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Therapeutic antiangiogenesis strategies have demonstrated significant antitumor efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be regarded as a promising technology for treatment of disease, especially cancer. In this study, vascular endothelial growth factor (VEGF)-small interfering RNA (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)-based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted, fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF gene silencing in vitro and in vivo. The prepared siRNA delivery system readily exhibited cellular internalization and ease of endosomal escape, resulting in excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in vivo experiments, notable retardation of tumor growth was observed in orthotopic ovarian tumor-bearing mice, which was attributed to significant inhibition of angiogenesis by systemic administration of this nanocarrier. No obvious toxic drug responses were detected in major organs. Further, the magnetic core of M-MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the ovarian cancer in mice on magnetic resonance imaging. Collectively, the results demonstrate that an M-MSN-based delivery system has potential to serve as a carrier of siRNA therapeutics in ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

Chen¹,

Wang

Liu

et al. 2015

IJN

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“…And yet, the NCCN lists intravenous-intraperitoneal chemotherapy as category 1 and allows intravenous carboplatin plus paclitaxel to enjoy category 1 status for those patients for whom intraperitoneal chemotherapy cannot be used (e.g., poor performance status). Meanwhile, despite showing an overall survival advantage in the Japanese randomized phase III trial, weekly dose-dense paclitaxel is listed as category 2A while the anti-angiogenesis agent, bevacizumab, has been relegated to category 3 notwithstanding four positive phase III randomized trials in advanced and recurrent disease [9].…”

Section: Editorialmentioning

confidence: 99%

New world order(s): Healthcare metrics, international borders, and gravitational waves

Tewari

2014

Gynecologic Oncology

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“…Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis. Inhibition of vascular endothelial growth factor receptors (VEGRs) can prolong survival for patients with ovarian and other cancers 5. Cediranib, a tyrosine kinase inhibitor, is an orally bioavailable inhibitor of VEGF signaling through the VEGR1, VEGR2, and VEGR3 receptors, and it has been studied in the management of several tumors 6, 7, 8, 9…”

Section: Introductionmentioning

confidence: 99%

Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial

Stark

Cook

Brown

et al. 2017

Cancer

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BACKGROUNDThe ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum‐sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health‐related quality of life (QOL) during the first year of treatment.METHODSFour hundred fifty‐six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent‐maintenance cediranib group.RESULTSThe rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent‐maintenance group (+4.5; 95% confidence interval, –2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self‐reported diarrhea.CONCLUSIONSThe 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression‐free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian cancer. Cancer 2017;123:2752‐61. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

Cited by 96 publications

References 65 publications

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

New world order(s): Healthcare metrics, international borders, and gravitational waves

Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial

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