Data for cediranib (RECENTINTM, AZD2171) presented at the annual meeting of the American Society of Clinical Oncology (ASCO) have demonstrated positive results in patients with recurrent glioblastoma (GBM), an invasive form of brain tumour with a high unmet need.1

Cediranib Phase II monotherapy study in recurrent glioblastoma (GBM)

Results from the National Cancer Institute (NCI) sponsored study at the Massachusetts General Hospital (MGH) Cancer Center, showed 8 patients (27.6%) of the 31 patients treated with cediranib with recurrent glioblastoma, the most aggressive form of primary brain tumour, were alive and progression-free at six months.1

Cediranib is a highly potent and selective VEGF signalling inhibitor that targets all three VEGF receptors.2 VEGF signalling is a key driver of angiogenesis - the formation of new blood vessels that tumours need to grow and spread. Cediranib is currently in Phase II/III development for advanced non-small cell lung cancer (NSCLC) and advanced colorectal cancer (CRC) - as well as being investigated as part of a wide-ranging signal search programme in other tumours such as glioblastoma.

Commenting on these results, Dr Tracy Batchelor, MD, chief of Neuro-Oncology in the Massachusetts General Hospital (MGH) Cancer Center, Associate Professor of Neurology at Harvard Medical School and lead author of the Phase II study said: "With currently available therapies such as chemotherapy, approximately 15% of patients with recurrent glioblastoma are typically progression free at six months. However, in this trial it was over a quarter of the patients. Median progression-free survival in those patients on the study was 111 days. This compares with the 63 days you would normally expect to see in recurrent glioblastoma patients receiving current standard therapies. These encouraging data warrant further investigation to validate these initial trial results."

"In addition, cediranib alleviated brain swelling (oedema) in many patients. Oedema is a debilitating symptom in many brain cancer patients and is currently treated with steroid drugs, which can carry their own debilitating side effects. Based on the first 16 patients a steroid-sparing effect was demonstrated in most patients and was associated with the normalisation of tumour vessels. This normalisation might help to secure delivery and improve effectiveness of other therapeutic techniques such as chemotherapy drugs and radiation therapy," said Dr Batchelor.

"The prognosis for recurrent glioblastoma patients is poor," commented AstraZeneca's Dr Nick Botwood, Global Medical Director for cediranib. "These are promising Phase II results and discussions are ongoing with Dr Tracy Batchelor and his group regarding a confirmatory study in recurrent glioblastoma."

Cediranib Phase II study in metastatic renal cell carcinoma (RCC)

Another ongoing NCI sponsored cediranib Phase II study presented at ASCO 2007 by investigators from the Princess Margaret Hospital in Toronto, looked at cediranib in first line, progressive, unresectable, advanced metastatic renal cell carcinoma (RCC).3

27 patients receiving cediranib as monotherapy were able to be evaluated for response with a response rate of 33% (9 out of 27 patients) and tumour control rates of 66.7% (18 out of 27 patients).3

"Renal cell carcinoma is a chemoresistant disease which has traditionally been difficult to treat, resulting in poor prognosis for patients hence these early data are encouraging," commented Professor S. Sridhar of the Princess Margaret Hospital Phase II Consortium, Toronto, Canada.

These results support another cediranib publication of RCC patients presented at ASCO 2007.4 In addition, an ongoing AstraZeneca sponsored Phase II, randomised study is currently investigating the efficacy of cediranib in patients with metastatic or recurrent RCC who have had no previous anti-VEGF therapy.

RECENTINTM is a trademark of the AstraZeneca Group of Companies.

About the National Cancer Institute

The National Cancer Institute coordinates the National Cancer Program, which conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.

The NCI is a component of the National Institutes of Health (NIH), one of eight agencies that compose the Public Health Service (PHS) in the Department of Health and Human Services (DHHS).

cancer

About cediranib

Cediranib is a once-daily, orally available, highly potent and selective VEGF signalling inhibitor that inhibits all three VEGF receptors.2

VEGF signalling is a key driver of angiogenesis - the formation of new blood vessels that tumours need to grow and spread. Cediranib inhibits this signal by binding to the intracellular domain of all three VEGF receptors, in particular VEGFR-2, the predominant receptor through which VEGF exerts its effects on angiogenesis, preventing the growth of new blood vessels.2 This effectively "starves" the tumour of the oxygen and nutrients it needs to grow.

Cediranib has shown encouraging signs of anti-tumour activity in a clinical development programme, which has included over 1,000 patients to date.

Phase I data indicate that cediranib is generally well tolerated, with the most common dose related adverse events being diarrhoea, hoarseness, headache and hypertension.5

Ongoing clinical trials with cediranib

Cediranib is being evaluated in an extensive ongoing clinical development programme including studies in lung and colorectal cancer as well as a range of other solid tumours:

Lung cancer

Lung cancer remains the biggest cause of cancer death worldwide. Over 1.35 million new cases of lung cancer are diagnosed every year and nearly 1.2 million people die as a result of this disease - more than breast, colon and prostate cancer combined.6

A Phase II/III study, BR24, being coordinated by the National Cancer Institute of Canada (NCIC), is comparing cediranib plus 'doublet' chemotherapy (paclitaxel and carboplatin) compared to 'doublet' chemotherapy alone in patients with advanced NSCLC.

Colorectal cancer

Colorectal cancer is the third most commonly reported cancer worldwide, with around 945,000 new cases and 492,000 deaths annually.7 It is ranked second in terms of both incidence and mortality in more developed countries.7

The Horizon Study Programme is ongoing to evaluate cediranib in patients with advanced colorectal cancer:

StudyPhaseDesignStage Horizon IIIII/IIICediranib in combination with FOLFOX compared to bevacizumab (Avastin®) in combination with FOLFOXPatients with first line advanced colorectal cancer Horizon IIIIICediranib plus standard chemotherapy compared to standard chemotherapy alonePatients with first line advanced colorectal cancer Horizon IIICediranib in combination with FOLFOX compared to bevacizumab in combination with FOLFOXPatients with second line metastatic colorectal cancer

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.475 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

References

1. Batchelor T et al. ASCO June 2007, Abstract no. 2001

2. Wedge et al., 2005 Cancer Research Paper Wedge SR et al: AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 65(10):4389-400.

3. Sridhar S et al. ASCO June 2007, Abstract no. 5093

4. van Herpen CML et al. ASCO June 2007 Abstract no. 3560

5. Drevs J, Medinger M, Mross K, Zirrgiebel U, Strecker R, Unger C, Puchalski TA, Fernandes N, Roberston J, Siegert P. Proceedings from ASCO 2005, Abs 3002

6. Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide IARC CancerBase No. 5. version 2.0, IARCPress, Lyon, 2004.

7. Stewart BW and Kleihues P (Eds): World Cancer Report. IARCPress. Lyon. 2003.

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