New Gefitinib Data - Furthering Understanding of Molecular & Genetic Basis for Anti-Cancer Activity

• First Data On Novel Anti-Angiogenesis Drug Also Reported By

AstraZeneca at AACR Meeting

• Carbone et al(1) reported a case of a non-small cell lung cancer (NSCLC) patient with progression following four chemotherapeutic regimens whodemonstrated a near-complete response to gefitinib sustained for 18 monthsbefore relapsing. Sequencing of the EGFR gene in the tumour after relapsedemonstrated a somatic mutation in the receptor and functional analysis ofthis mutant is in progress.

• In a preclinical study reported by Benavente et al(2), cells were maderesistant to gefitinib or to the EGFR monoclonal antibody (MAb), cetuximab.The results showed cells which were made resistant to the EGFR MAb stillresponded to gefitinib; conversely cells made resistant to gefitinib did notrespond to EGFR MAb.

• Hayama et al(3) reported initial findings from a study aimed atidentifying genes which could be important in the onset of gefitinibresistance.

• Changes in biomarkers associated with the decrease in cell growth andsurvival following gefitinib were reported by Speake(4) at al; these datacontribute further to understanding the mode of action of gefitinib.

• Results of a study assessing ZD6474 effect on lung angiogenesis andmetastasis in an orthotopic model of non-small cell lung cancer that closelymimics the patterns of clinical disease. Herbst et al(5) reported that ZD6474resulted in almost complete suppression of growth, invasion and metastasis ofestablished lung tumours.

• A second study by Nishio et al(6) assessed the antitumour effect in aVEGF-producing primary gastric cancer model, and showed that ZD6474 treatmentresulted in tumour regression and reduced tumour dissemination.

• Research evaluated anti-tumour and anti-angiogenic activity in aspontaneous breast carcinoma model. Klinowska et al(7) reported results thatshowed a significant inhibition in tumour growth even at very low doses(0.75mg/kg/day). In established disease, AZD2171 also restricted tumourgrowth and at higher doses caused tumour regression.

• Drevs et al(8) presented data which showed that, in a model of kidneycancer, AZD2171 significantly inhibited primary tumour growth, metastaticspread and the development of tumour blood vessels, and had superior potencyto all other VEGF inhibitors previously tested in this model.

• An additional study by Bradley et al(9) reported the impact of AZD2171 on VEGF-dependent vascular permeability in tumours in an human colon tumourmodel. Results showed significant reduction in tumour vascular permeabilityand vascular volume demonstrating direct effects of AZD2171 on tumour bloodvessels.

• IRESSA(tm) is a trademark of the AstraZeneca group of companies.

• For further information on the Epidermal Growth Factor Receptor and its

potential role in cancer treatment, please visit www.EGFR-INFO.com

• For further information on gefitinib and lung cancer, please visit

www.iressa.com

• For further press information regarding gefitinib and other AstraZeneca

cancer therapies, please visit www.astrazenecapressoffice.com

EGFr. Abstract Number 2464. 95th AACR, March 2004

growth factor receptor (EGFR) inhibitors in human tumor cells.

Abstract Number 5333. 95th AACR, March 2004

resistance. Abstract Number 4548. 95th AACR, March 2004

erbB2 and EGFR inhibitors. Abstract Number 4653. 95th AACR, March 2004

and EGF receptor signaling, inhibits lung angiogenesis and metastasis

and improves survival in an orthotopic model of non-small cell lung

cancer. Abstract Number 4551. 95th AACR, March 2004

primary gastric cancer model. Abstract Number 4537. 95th AACR, March 2004

receptor tyrosine kinase activity, inhibits the growth of spontaneous

mammary tumours in the MMTV-neu transgenic mouse. Abstract Number 4540.

95th AACR, March 2004

tyrosine kinase inhibitor, on primary tumour growth, metastasis and

vessel density in murine renal cell carcinoma. Abstract Number 4554.

95th AACR, March 2004

compromise hemodynamic parameters in an SW620 human colon tumour model:

an analysis using perfusion-permeability dynamic contrast-enhanced

magnetic resonance imaging (pp-DCE-MRI). Abstract Number 4552. 95th

AACR, March 2004

--Distributed by AsiaNet (www.asianetnews.net)--

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