Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer

Matulonis, Ursula A.; Berlin, Suzanne; Krasner, Carolyn; Tyburski, Karin; Lee, J.; Roche, Maria; Ivy, S. Percy; Lenahan, Corrine; King, Michelle; Penson, R. T.

doi:10.1200/jco.2008.26.15_suppl.5501

Cited by 21 publications

(12 citation statements)

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“…Patient demographics are summarized in Table 1. A total of 150 cycles of therapy were administered (median, 6; range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. All patients were evaluable for toxicity and 14 patients were evaluable for response.…”

Section: Resultsmentioning

confidence: 99%

Phase I Study of Cediranib in Combination with Oxaliplatin and Infusional 5-Fluorouracil in Patients with Advanced Colorectal Cancer

Chen

Jonker

Gauthier

et al. 2009

Clinical Cancer Research

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Purpose: Cediranib is a potent oral inhibitor of the tyrosine kinase activity associated with all subtypes of vascular endothelial growth factor receptor. Purposes of this study were to determine the recommended phase II dose of cediranib in combination with standard doses of modified FOLFOX-6 (mFOLFOX-6), and the tolerability, safety, pharmacokinetics, and antitumor activity of this combination in patients with untreated metastatic colorectal cancer. Experimental Design: Cediranib was administered daily orally at a starting dose of 30 mg and escalated to 45 mg daily, and mFOLFOX-6 was repeated every 14 days. Pharmacokinetic studies were done for oxaliplatin, 5-fluorouracil, and cediranib. Response was assessed by Response Evaluation Criteria in Solid Tumors every four cycles. Results: Sixteen patients received 150 cycles of treatment (median, 6; range, 1-20 cycles). Of 9 patients enrolled at the 30-mg dose level, 1patient experienced grade 3 diarrhea during cycle 1. No dose-limiting toxicity was observed in 7 patients at the 45-mg dose level. Common grade 3 toxicities related to cediranib included hypertension, diarrhea, fatigue, and anorexia. Of 14 patients evaluable for response, there were 6 partial responses (42.9 %; 95 % confidence interval, 17.7-71.1%) and 6 stable disease. The median progression-free survival was 9.3 months. There were no pharmacokinetic interactions between cediranib and 5-fluorouracil or free plasma intact oxaliplatin. Conclusions: Toxicities of this combination were manageable and consistent with previous studies. The recommended phase II dose is cediranib at 30 mg daily continuously in combination with standard doses of mFOLFOX-6. Cediranib and mFOLFOX-6 has promising antitumor activity and this combination warrants further investigation.

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Section: Resultsmentioning

confidence: 99%

Phase I Study of Cediranib in Combination with Oxaliplatin and Infusional 5-Fluorouracil in Patients with Advanced Colorectal Cancer

Chen

Jonker

Gauthier

et al. 2009

Clinical Cancer Research

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“…Cediranib (AZD2171), which targets VEGFR1, VEG-FR-2 and VEGFR-3, has shown activity in recurrent or persistent ovarian cancer in two phase II trials [29,30]. This agent is now being tested in platinum-sensitive relapsed ovarian cancer in a three-arm randomised placebo-controlled phase III trial in combination with carboplatin and paclitaxel (ICON-6).…”

Section: IImentioning

confidence: 98%

Current status of anti-angiogenic agents in the treatment of ovarian carcinoma

et al. 2009

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During the last decade we have assisted in the development of new therapeutic strategies for the treatment of ovarian cancer, based on the best knowledge of molecular biology. One of the most promising strategies under investigation is antiangiogenic therapy. Bevacizumab is a monoclonal humanised antibody targeting vascular endothelial growth factor (VEGF), which has shown antitumour activity in ovarian cancer in preclinical models as well as in clinical trials, both in monotherapy and in combination with other therapies. Currently, ongoing phase III trials are testing bevacizumab as a front-line therapy with carboplatin and paclitaxel. Bevacizumab has been generally well tolerated with mild frequent toxicities (proteinuria, hypertension and bleeding). However, the drug may result in other uncommon, but potentially life-threatening side effects, such as arterial thromboembolism, wound healing complications, and gastrointestinal perforation or fistulae, which should be considered when the drug is administered. Other new therapeutic antiangiogenic strategies that include small-molecule tyrosine kinase inhibitors, antibodies neutralising the VEGF receptor (VEGFR) and soluble VEGFR hybrids (VEGF Trap) are being investigated with promising early results.

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“…For example, two grade 4 cerebral haemorrhages in patients without evidence of brain metastases occurred in phase 1 or 2 studies of cediranib. 23,83 Overall, the incidence of haemorrhagic events in patients other than those with NSCLC receiving VEGF RTKIs vandetanib, SU6668, and pazopanib seems to be similar to the incidence in those receiving placebo. This also seems to be the case with imatinib, EGFR-targeted agents, fosbretabulin, and DMXAA.…”

Section: Haemorrhagementioning

confidence: 88%

Collateral damage: toxic effects of targeted antiangiogenic therapies in ovarian cancer

Stone¹,

Sood²,

Coleman³

2010

The Lancet Oncology

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First-line chemotherapy fails in more than 20% of patients with epithelial ovarian cancer and about 40–50% of women who respond to initial treatment relapse within 2 years. In the recurrent setting, second-line chemotherapeutic agents have a 15–20% response rate with no cures. Fortunately, clinical investigations that have assessed the efficacy of new, biologically targeted therapies have reinvigorated therapeutic options for patients living with ovarian and other malignancies. In view of the fact that ovarian cancer is one of the most angiogenic neoplasms, there is great hope that implementing targeted agents with antiangiogenic properties will improve outcomes. However, as experience grows with the antitumour activity of these drugs, new toxic effects are emerging. The effects of antiangiogenic agents on molecules and processes that also have physiologically important roles in healthy tissues are at the crux of these toxic effects, or “collateral damage”. This review discusses the leading toxic effects encountered and anticipated in clinical investigation and practice with antiangiogenic agents in patients with ovarian cancer, with particular focus on potential management strategies.

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Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer

Cited by 21 publications

References 0 publications

Phase I Study of Cediranib in Combination with Oxaliplatin and Infusional 5-Fluorouracil in Patients with Advanced Colorectal Cancer

Phase I Study of Cediranib in Combination with Oxaliplatin and Infusional 5-Fluorouracil in Patients with Advanced Colorectal Cancer

Current status of anti-angiogenic agents in the treatment of ovarian carcinoma

Collateral damage: toxic effects of targeted antiangiogenic therapies in ovarian cancer

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