A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer

Friedlander, Michael; Hancock, Kenneth C.; Rischin, Danny; Messing, Mark J.; Stringer, C. Allen; Matthys, Gemma M.; Ma, Bo; Hodge, Jeffrey; Lager, Joanne

doi:10.1016/j.ygyno.2010.05.033

Cited by 218 publications

(118 citation statements)

References 38 publications

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“…For example, pazopanib is an oral angiogenesis inhibitor that inhibits VEGF receptor, platelet-derived growth factor receptor and c-Kit. In a phase II study evaluating pazopanib in patients with recurrent ovarian cancer, the overall response rate was 18% and the median response duration was 113 days (25,26). A recent phase III clinical trial (AGO-OVAR16) showed that pazopanib extended PFS by an average of 5.6 months (17.9 months vs. 12.3 months), compared with a placebo, in women with advanced ovarian cancer who underwent initial successful treatment, while the interim analysis showed no difference in OS between the groups (27).…”

Section: Discussionmentioning

confidence: 99%

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

Kinose

Sawada

Makino

et al. 2015

Molecular Cancer Therapeutics

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The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by antiangiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost effective for use in all patients. Therefore, the development of a novel antiangiogenic drug, especially composed of smallmolecule compounds, could be a powerful armament for ovarian cancer treatment. As NF-kB signaling has the potential to regulate VEGF expression, we determined to identify whether VEGF expression is associated with NF-kB activation and to investigate the possibility of a novel IKKb inhibitor, IMD-0354 (IMMD Inc.), as an antiangiogenic drug. Tissue microarrays from 94 ovarian cancer tissues were constructed and immunohistochemical analyses performed. We revealed that IKK phosphorylation is an independent prognostic factor (PFS: 26

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Section: Discussionmentioning

confidence: 99%

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

Kinose

Sawada

Makino

et al. 2015

Molecular Cancer Therapeutics

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“…These changes are hypothesized to result in improved delivery of oxygen, nutrients, and cytotoxic chemotherapy to the tumor [43]. Table 1 details notable phase 2 studies of anti-angiogenesis therapy in EOC [44][45][46][47][48][49][50][51][52][53][54]. Of the 6 molecules studied, 5 have been advanced to the phase 3 arena.…”

Section: Phase 2 Studiesmentioning

confidence: 99%

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

Eskander

Tewari

2014

Gynecologic Oncology

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“…Pazopanib is more intriguing. An oral multikinase inhibitor with antitumor and antiangiogenic effects, pazopanib has demonstrated comparable efficacy to bev in the maintenance setting [22] and also appears to have activity in relapse [23].…”

Section: New Agentsmentioning

confidence: 99%

Breaking Down the Evidence for Bevacizumab in Ovarian Cancer

Shu

Konner

2015

The Oncologist

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In 1971, Judah Folkman prophesized thatantivascular therapies could be used to fight cancer [1]. Since the 1990s, vascular endothelial growth factor (VEGF) has been recognized as a critical element in tumor angiogenesis and as an adverse factor in ovarian cancer (OC) [2]. It has now been 10 years since the U.S. Food and Drug Administration (FDA) initially approved bevacizumab (bev), the anti-VEGF monoclonal antibody that became one of the top-selling cancer drugs in the world. Its approved indications include colorectal, lung, kidney, cervix, and (previously) breast cancers, and it has been used widely as a standard therapy for OC for more than 5 years. Bev is licensed by the European Medicines Agency for use in first-line, first platinum-sensitive recurrence, and platinum-resistant OC. Bev was recently FDA approved for use in combination with singleagent chemotherapy for platinum-resistant disease; however, its optimal role in this cancer remains unclear. SINGLE-AGENT ACTIVITYIn early phase II trials, bev yielded single-agent activity beyond that seen in colorectal or lung cancer [3,4]. The addition of oral daily "metronomic" cyclophosphamide appeared to increase responses even further [5]. The initial enthusiasm generated was blunted, however, when an increased risk of gastrointestinal (GI) perforation was detected. In a study intended for registration, Cannistra et al. [6] evaluated bev in platinum-resistant OC and noted a median progression-free survival (PFS) of 4.4 months. The study was halted because of an 11.4% incidence of GI perforation, and a black box warning from the FDA ensued. Meta-analyses confirmed an increased risk of perforation and treatment-related mortality in a variety of cancer types [7,8].Since then, efforts to identify predictors of adverse GI events have successfully aided patient selection in clinical practice. Some of the compelling red flags in ovarian cancer include high-volume peritoneal carcinomatosis enveloping the bowel and history of malignant bowel obstruction. For patients receiving front-line therapy, history of treatment for inflammatory bowel disease and bowel resection at primary surgery [9] appear to increase risk. Presently, the risk of GI perforation from bev in recurrent OC is likely closer to 3% rather than the 11% observed in the population treated by Cannistra et al. [6]. RECURRENT DISEASEOCEANS [10] was a randomized phase III trial testing the combination of gemcitabine and carboplatin with or without the addition of bev given concurrently and then as maintenance until progression in platinum-sensitive OC. PFS for the bev arm was 12.4 months (vs. 8.4 months; p , .001). By the final analysis, however, there was no difference in overall survival (OS; 33.6 vs. 32.9 months) [11]. Of note, nearly all of the women in both arms went on to receive additional therapy, including bev.In the AURELIA trial [12], bev was combined with the investigator's choice of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, topotecan), in platinum-resistant OC...

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A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer

Cited by 218 publications

References 38 publications

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

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

Breaking Down the Evidence for Bevacizumab in Ovarian Cancer

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