Expanding Boundaries in the Development of New Cancer Treatments: AstraZeneca Pharmaceuticals, LP

PREVIEWS IN UROLOGY Expanding Boundaries in the Development of New Cancer Treatments: AstraZeneca Pharmaceuticals, LP A straZeneca Pharmaceuticals, LP is one of the top five pharmaceutical companies in the world and among the industry leaders in providing products for treating gastrointestinal, oncologic, cardiovascular, central nervous system, and respiratory diseases. Many of the more than 10,000 U.S. employees of AstraZeneca are involved in developing hormonal therapies for the treatment of breast and prostate cancers. Building on achievements such as marketing the world’s most prescribed anticancer drug (the standard treatment for breast cancer) and a best-selling hormonal treatment for prostate cancer, AstraZeneca continues to pioneer new treatment strategies for these devastating diseases. Efforts include the discovery of entirely new classes of compounds, in addition to fully exploiting the potential of existing agents to improve the quality and length of life for cancer patients A Tradition of Success in Breast and Prostate Cancer The approach by AstraZeneca to cancer treatment is to attack the disease process at each point along its continuum of progression, from the earliest to the most advanced stages. Our hormonal treatment for both early and advanced breast cancer is the most widely accepted endocrine therapy for the disease in premenopausal and postmenopausal women. It is also used to reduce the incidence of breast cancer in women at high risk for the disease and to treat ductal carcinoma in situ (DCIS), a very early form of breast cancer confined to cells lining the milk ducts. For prostate cancer, one AstraZeneca hormonal treatment lowers levels of testosterone, thus reducing the risk of hormone-dependent tumor growth and providing men with prostate cancer an alternative to orchiectomy. It can be used either for advanced prostate cancer or, in combination with other hormonal treatments and radiation therapy, for management of locally confined disease. In the 1970s and 1980s, research in the hormonal treatment of prostate cancer led to a new class of compounds that preferentially block the androgen receptor and prevent prostate cancer cell growth. By decreasing or eliminating the influence of adrenal as well as testicular androgens, these newer hormonal treatments, used in combination with existing treatments, may exert an additive effect on preventing the growth of prostate cancer. The New Prostate Cancer Patient Earlier testing and closer patient monitoring have caused a shift in the population for whom hormonal therapy is prescribed, changing concepts of treatment. Traditionally, hormonal therapy was reserved until late in the natural history of the disease, after metastatic bone involvement had developed. Prostate cancer patients experiencing painful symptoms received treatment for approximately 3 years, until death. Today, hormonal therapy is being used earlier for poorrisk patients with locally advanced disease and for patients whose prostate-specific antigen (PSA) level rises after definitive treatment of curative intent. The median life expectancy of these patients is far longer—10 to 15 years. The potential of hormonal therapy in combination with radical prostatectomy and radiation (ie, as adjuvant treatment) is currently being assessed for less advanced disease by AstraZeneca. Because prostate cancer today is diagnosed at an earlier stage in younger men, adjuvant hormonal therapy is being tested in the largest ongoing program of prostate cancer trials to date. More than 8,000 patients, on four continents, are enrolled in three randomized, controlled clinical trials evaluating adjuvant hormonal treatment versus placebo for early, nonmetastatic disease. By treating prostate cancer earlier, the disease may be prevented from spreading to other parts of the body, when it becomes more difficult to treat effectively. The benefits of early hormonal treatment on prostate cancer are not yet fully known, and final results of these trials are eagerly anticipated. New Approaches to Unlocking Cancer’s Secrets AstraZeneca is continuing its 40-year commitment to the basic research that brings about effective new treatments. Among the 20 different anticancer compounds currently being developed by AstraZeneca, backed by an investment of $280 million in 1999 and the efforts of thousands of dedicated employees, are these: Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor: An inhibitor of cancer invasion, this investigational agent works unlike any approved cancer treatment. Orally administered, it selectively blocks signaling pathways within cancer cells needed for their survival and growth. This compound has shown promising activity in a broad spectrum of tumor types, including nonsmall cell lung and prostate cancers; it is currently being investigated in clinical trials for the most common form of lung cancer. Estrogen Receptor Down-Regulator (ERD): Introducing an entirely new class of drug for the treatment of breast cancer, ERD downregulates the estrogen receptor protein itself, rather than altering estrogen receptor activity. Clinical trials have investigated its use for patients with advanced breast cancer whose tumors fail to respond to standard therapy. Antiangiogenics: A new compound designated ZD6474 targets signaling pathways that supply tumor cells with oxygen and nutrients. Phase I trials in a number of different tumors are currently under way. A second agent in development that acts to prevent cancer cells from gaining a blood supply is ZD6126. By disrupting the vascular endothelium, ZD6126 causes vessels supplying blood to cancer cells to close, resulting in tumor cell death. Phase I clinical trials with ZD6126 have just begun. The Future The research and development of new anticancer agents is often a prolonged and uncertain enterprise. A promising new compound may fail at any point in the 5- to 7-year testing process required before it can be marketed in the United States. The investment in time and human resources is exceeded only by the monetary expenditure. Despite the risks of drug discovery and development, persistent and rational clinical investigation is the only reliable method of bringing effective new treatments to those who need them. The record achieved by AstraZeneca for providing safe and effective cancer treatments will, likewise, continue as it generates innovative medicines for the management of various types of cancer. To learn more about our products please visit our web site at www.AstraZeneca-us.com. Previews in Urology highlights topics of interest to urologists through the points of view of the companies that sponsor publication of this journal; the material has not been reviewed by the Medical and Contributing Editors.