FIRST HUMAN TRIALS OF PLATELET GROWTH FACTOR PRESENTED

Embargoed for 12:50 p.m. May 19, 1996 BR> Media Contact: Sarah Goodwin at 404/727-5686, e-mail: sgoodwi@emory.edu

Emory University Investigator Reports Phase I/II Trial Results at American Society of Clinical Oncology (ASCO) Annual Meeting In Philadelphia

For more than 40 years, oncologists have wrestled with the ravages that chemotherapy inflicts on healthy blood cells. Now, the nation's first human clinical trial of a natural protein that stimulates the body to produce more blood platelets has been completed at Emory University's Winship Cancer Center, UCLA Medical Center and Duke University. The novel growth factor, called pegylated recombinant human megakaryocyte growth and development factor (MGDF), may be extremely important for cancer patients because chemotherapy drugs that help control tumor cell growth can also dangerously deplete platelet levels. Platelets are a vital component of blood, enabling it to clot properly; low levels can leave a patient at risk for excessive bruising, internal bleeding and even intracerebral hemorrhaging. Previous animal studies at Emory have shown that MGDF is effective in restoring platelet levels to normal, permitting administration of larger doses of therapeutic drugs. At the annual meeting of the American Society of Clinical Oncology, principal investigator Michael Fanucchi, M.D., associate professor of medicine, Emory University, presented results from this multi-center Phase I/II study conducted at Emory, UCLA and Duke. Fifty U.S. lung cancer patients received carboplatin and paclitaxel chemotherapy followed by MGDF or placebo. The clinical trial focused on patients with newly diagnosed stage III (extensive tumors within the chest) and stage IV (tumors that have spread outside the chest) non-small cell lung cancer. Patients with a history of heart disease, stroke or brain metastasis were not eligible for the study. The study showed that MGDF was generally well tolerated, with no systemic toxicities, and that MGDF decreased the duration and severity of thrombocytopenia. Based on this study, MGDF may prove to be an important treatment for people with cancer receiving intensive chemotherapy, Dr. Fanucchi said. The most significant results were the rapid return to baseline platelet count and the higher platelet nadir for patients in the MGDF-treated groups. After chemotherapy, the median return time to baseline platelet count in the MGDF- treated patients was 13 days; the platelet count of the placebo group did not recover to baseline before the next cycle of chemotherapy. Also, post- chemotherapy the median platelet nadir (lowest count) for all the MGDF patients was 189,000 per cubic millimeter of blood (cmm), which was 70 percent higher than the placebo group whose platelet count dropped to 111,000/cmm. Pre- chemotherapy the platelet counts of both groups were the same. Normal platelet counts range between 150,000 and 450,000/cmm. The substance that drives platelet production, thrombopoeitin, was identified only recently. Scientists at the Amgen and Kirin pharmaceutical companies have now succeeded in engineering the gene product to administer it for therapeutic use in larger quantities than it is normally produced in the body. "The genes that control red and white blood cell production have already been cloned, which gave rise to drugs that counteract the effects of chemotherapy on those cells," says Dr. Fanucchi. "Platelets were the missing link." Carboplatin, a drug commonly used for the treatment of lung cancer, can wreak havoc with platelets, sometimes reducing the count to 50,000 pcm or lower. Patients in the study were treated with the combination of carboplatin and paclitaxel. Platelets were counted daily to assess MGDF's effect on platelet production. About 75 percent of all lung cancer patients have non-small cell cancer. Of all non-small cell patients, the majority (about 60 percent) have already reached stage III or IV by the time they are diagnosed, when chemotherapy is important to prolong survival. Lung cancer is the leading cause of cancer death in both men and women. Approximately 158,700 people will die from lung cancer in 1996, and an additional 177,000 new cases will be diagnosed, according to American Cancer Society estimates. Since 1987, more women have died each year of lung cancer than from breast cancer, which for more than 40 years was the major cause of cancer death in women. The incidence rate in women continues to increase, while in men, incidence decreased in 1991 for the first time in several decades. The Winship Cancer Center of Emory University is dedicated to the integration of innovative clinical and basic research with outstanding patient care for the prevention, treatment and control of cancer. The Winship Cancer Center is part of the Robert W. Woodruff Health Sciences Center of Emory University.

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