Platelet destruction resulting from chemotherapy is a problem oncologists have been grappling with for years. Animal studies at Emory have shown that the new protein, called megakaryocyte growth and development factor (MGDF), is extremely effective in restoring platelet levels to normal, thereby permitting the animals to withstand larger doses of tumor-killing chemotherapy drugs. Larger doses of these agents may shrink tumors in humans more effectively and increase the chance of remission.
Platelets are a vital component of blood that enable it to clot properly. With a faulty clotting mechanism, injuries that otherwise would produce little or very moderate bleeding can result in life-threatening bleeding. The gene that drives platelet production was only identified recently. Scientists at the Amgen and Kirin pharmaceutical companies have now succeeded in engineering the gene product, MGDF, to administer it for therapeutic use in larger quantities than are normally produced in the body.
"We are very excited about the clinical trial," said Michael Fanucchi, associate professor of medicine, who is leading the study here. "The genes that control red and white blood cell production have already been cloned, which gave rise to drugs that can counteract the effects of chemotherapy on these cells; platelets were the missing link. MGDF may help many types of cancer patients get the chemotherapy they need to stay in remission longer."
A healthy person's platelet count ranges between 150,000 and 450,000 per cubic millimeter (pcm) of blood. Carboplatin, a staple in a standard lung chemotherapy "cocktail," can wreak havoc with platelets, sometimes reducing the count to 50,000 pcm or lower.
A platelet count of 10,000 to 20,000 could induce internal bleeding or bruising. Sinking below 10,000 platelets is extremely dangerous, and at worst, can result in intracerebral hemorrhaging.
In the trial, platelets will be counted and checked for function daily to assess the drug's effect and to prevent overproduction of platelets, which could potentially lead to blood clots. Platelet levels drop to normal when administering of the drug is stopped. Physicians also will monitor closely the effect of MGDF on mature platelets already present in the blood, which carry receptors for the MGDF molecule. There are no outward symptoms or feelings of discomfort when platelet counts rise slightly, so with careful monitoring, researchers hope the drug will be well-tolerated.
The Winship Cancer Center's new clinical trial is aimed at 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 who have a history of heart disease, stroke or brain metastasis are not eligible for the study. 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. About 157,400 people will die of lung cancer in 1995, and an additional 169,900 new cases will be diagnosed, according to American Cancer Society estimates. Since 1987, more women have died each year of lung cancer than 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 the rate decreased in 1991 for the first time in several decades.
-- Kate Egan