AstraZeneca's IRESSAT -- ZD1839 -- Demonstrates Encouraging Antitumor Activity in Non-small Cell Lung Cancer.

Health & Medical Editors

NEW ORLEANS--(BW HealthWire)--May 23, 2000

Data Presented Today at the American Society of Clinical Oncology

(ASCO) Annual

Meeting in New Orleans

Final results from Phase I clinical trials released today, show that in a small number of patients, the novel anticancer compound made by AstraZeneca, known as IRESSAT or ZD1839, shows encouraging antitumor activity or disease stabilization, particularly in non-small cell lung cancer(1). The data were presented today at the American Society of Clinical Oncology (ASCO) annual meeting in New Orleans.

"From these preliminary trials, our results show that IRESSA demonstrates encouraging antitumor activity, particularly in non- small cell lung cancer. Ongoing trials will help us determine the best dose and how IRESSA can be combined with other cancer treatments including chemotherapy," said Dr. David Ferry, Medical Oncologist, CRC Institute for Cancer Studies, University of Birmingham, UK.

"AstraZeneca is encouraged by IRESSA's progress in early research. As a company, we have been committed to cancer research for over 20 years and it is exciting to see these new approaches to treating cancer come to fruition. It is critical that we all support participation in clinical trials in order for IRESSA and other promising medications to be fully developed," stated Dr. George Blackledge-Medical Director of Oncology at AstraZeneca.

The authors reported final results from a Phase I dose escalation trial intended to evaluate the tolerability and activity of IRESSA in patients with solid malignant tumors known to express or over-express epidermal growth factor receptors (EGFR). Escalating doses of IRESSA (50-mg to 700-mg once daily) were given orally for 14 days followed by 14 days' observation.

In the absence of progression or dose- limiting toxicity, IRESSA was re-initiated at the same dose. A total of 64 patients (25 male, 39 female; median age 54) were enrolled in the trial and all had received, and progressed on, at least one prior chemotherapy regimen.

The authors concluded that IRESSA was well tolerated, demonstrated predictable pharmacokinetics compatible with once-daily oral administration, and showed encouraging antitumor activity, particularly in non-small cell lung cancer. Overall, 15 patients with a range of tumor types had stable disease or response for 4 months.

Antitumor activity was most evident among the 16 non-small cell lung cancer patients (see table). The most common adverse events were mild to moderate diarrhea and acne-like skin rash. Serious adverse events were rare and usually related to disease progression. Dose-limiting toxicity was observed at the 700-mg dose level (G3 diarrhea).

Response               No. Patients   Dose     Response / Anti-
                            NSCLC               tumor activity
                           (n=16)


Partial response              2      300-mg        9+ months
                                     525-mg        6+ months
Confirmed significant         2      400-mg        2  months
 disease regression                  700-mg        6+ months
Stable disease                2      225-mg        5  months
                                     525-mg        5+ months

Background on IRESSAT (ZD1839)

IRESSA has been designed to block one of the important chemical pathways implicated in a variety of solid tumors and is one of several novel approaches to treating cancer that AstraZeneca is investigating. The mechanism of action is unlike other cancer treatments, including hormonal therapy and cytotoxic chemotherapy agents.

It works by blocking signals within the cancer cells, thus preventing a series of chemical reactions that cause or signal the cell to grow and divide.

The chemical pathway that IRESSA is designed to target is triggered by an epidermal growth factor which binds to a receptor on the cell surface called the epidermal growth factor receptor or EGFR. The EGFR sends signals within the cell via a signal-transmitter enzyme called tyrosine kinase (TK), which instructs the cell to grow and divide.

IRESSA blocks this TK enzyme, effectively switching off the signals from the EGFR. This potentially stops the cancer from growing. Simply called an EGFR-TK inhibitor, IRESSA is administered as a once-daily oral tablet.

Clinical data suggest that increased levels of EGFR are linked to poor prognosis, including tumor invasion and development of metastases (cancer spread from the site of origin to other organs and areas of the body) in some types of cancer. EGFR is expressed or over-expressed in a variety of common solid tumors including non- small cell lung cancer (NSCLC).

Pre-clinical research results from a number of studies on IRESSA have shown promising activity in a broad spectrum of tumor types both as monotherapy and in combination with commonly used cytotoxic agents. Research on IRESSA is continuing and depending on the results, AstraZeneca hopes to file new drug applications worldwide within the next few years. IRESSA is currently not on the market in any country.

AstraZeneca now intends to significantly widen the research program for IRESSA to allow wider access to future clinical trials to establish the safety and efficacy of the agent. Phase III studies in advanced non-small cell lung cancer are scheduled to commence over the next few months.

Background on AstraZeneca

AstraZeneca continues its tradition of research excellence and innovation in Oncology that led to the development of its current anticancer therapies including: NOLVADEX(R) (tamoxifen citrate) Tablets, CASODEX(R) (bicalutamide) Tablets, ZOLADEX(R) (goserelin acetate implant), and ARIMIDEX(R) (anastrozole) Tablets.

The company is currently involved in research and development of a number of novel approaches to the treatment of cancer, including anti-proliferation, anti-angiogenesis, vascular targeting technology and anti-invasion agents. Presently the company has 20 different anti-cancer projects in research and development.

AstraZeneca (NYSE:AZN) is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services.

It is one of the top five pharmaceutical companies in the world with healthcare sales of $15 billion and leading positions in sales of gastrointestinal, oncology, anesthesia including pain management, cardiovascular, central nervous system (CNS) and respiratory products. In the United States, AstraZeneca is a $7.4 billion healthcare business with approximately 9,500 employees.

NOTES: For further information, please contact Mary Lynn Carver at

[e-mail] or on 302/886-7859.

Alternatively, please visit the World Wide Web for the

following information:

-- Epidermal growth factor receptors (EGFR) and their

potential role in the treatment of cancer:

www.EGFR-info.com

-- Full prescribing information on marketed drugs:

www.astrazeneca-us.com

Facts About Lung Cancer:

-- Lung cancer is the leading cause of cancer-related death

in the United States for both men and women, accounting

for 28% of all cancer deaths.(2) This year, an estimated

156,900 men and women will die from lung cancer(2).

-- Lung cancer is the second most commonly occurring cancer

in both men and women,(3) and an estimated 164,100 new

cases of lung cancer will be diagnosed in the US in 2000;

89,500 among men and 74,600 among women(2). This

represents 14% of all cancer diagnoses(2).

-- The rate of lung cancer cases appears to be declining

among white and black men in the US, while it continues to

increase among both white and African-American women(3).

Decreasing incidence and mortality rates are most likely

the result of decreasing smoking rates over the past 30

years. However, decreasing smoking patterns among women

are lagging behind those of men.

(1) Ferry D, Hammond L, Ranson M, Kris M, Miller V, Murray P, Tullo A,

Feyereislova A, Averbuch S, Rowinsky E. Intermittent oral ZD1839

(Iressa), a novel epidermal growth factor receptor tyrosine kinase

inhibitor (EGFR-TK), shows evidence of good tolerability and

activity: Final results from a Phase I study. Presentation,

American Society of Clinical Oncology Annual Meeting, New Orleans,

May 23, 2000.

(2) American Cancer Society; Cancer Facts & Figures-2000 Special

Section: Lung Cancer.

(3) American Lung Association; Facts About Lung Cancer:

www.lungusa.org (accessed 05.01.00).