Growth factor stimulates platelet
count after chemotherapy

Cancer patients who received a novel growth factor after undergoing chemotherapy showed a 70 percent increase in blood platelet levels compared to patients not exposed to the growth factor, Emory researchers and others reported in The New England Journal of Medicine. In addition, platelet counts of exposed patients returned to normal levels significantly faster than did counts in patients unexposed to the growth factor.

"Our findings suggest that for the first time doctors have the means to stimulate the production of platelets depleted by chemotherapy," said principal investigator Michael Fanucchi, an associate professor in the Department of Medicine. "Not only may giving the growth factor after chemotherapy reduce risks associated with low platelet counts such as bleeding, it may also allow oncologists to use chemotherapeutic agents more effectively by administering stronger or more frequent doses."

The investigational growth factor is polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor (MGDF). It is Amgen Inc.'s proprietary, recombinant human form of the major regulator of platelets in the blood. Amgen, of Thousand Oaks. Calif., isolated and cloned MGDF and has refined a method of utilizing recombinant technology to manufacture large quantities of the platelet-producing protein.

During the Phase I/II randomized and double-blinded clinical trial, investigators at Emory, UCLA and Duke University evaluated the tolerance and effect on platelets of MGDF in persons with advanced nonsmall-cell lung cancer. After all 53 patients underwent chemotherapy with paclitaxel (Taxol) and carboplatin, 40 received MGDF and 13 received placebo.

Among 38 MGDF patients, the researchers documented a median low platelet count of 188,000 per cubic millimeter-a 70 percent increase over the median low count of 111,000/cmm measured among the unexposed patients. Still more important to the researchers was the finding that platelet counts in the MGDF patients returned to normal within 14 days-a significantly more rapid recovery than the 21 days or longer measured among patients receiving placebo. Two of the patients developed blood clots, perhaps related to the increased platelet production induced by MGDF.

Platelets are disc-shaped components of blood that are smaller than red blood cells and contain no hemoglobin. They promote clotting; therefore, when low, the body is at risk for excessive bruising and bleeding. Many chemotherapeutic agents, including carboplatin, can reduce platelet counts to dangerous levels (50,000/cmm or lower). Low platelet counts can be corrected by transfusions. Transfusions, however, bring further risks of possible infectious or allergic complications.

"The development of MGDF represents a potentially important addition to the armamentarium for managing patients receiving myelosuppresive chemotherapy," said Laurence A. Harker, director of the Division of Hematology-Oncology in the Department of Medicine and a co-author of the paper. "It can be combined with other growth factors such as G-CSF, which stimulates production of white blood cells, and erythropoietin, which drives the production of red blood cells."

The majority of lung cancer patients have nonsmall-cell cancer that is not diagnosed until the later stages, stages III and IV, when chemotherapy is especially vital to prolonging survival. "We look forward to expanding the role of this agent in future chemotherapeutic trials," said Christopher D. Hillyer, deputy director of Winship Cancer Center.

Lung cancer is the leading cause of cancer death in men and women. Approximately 160,400 Americans will die from lung cancer in 1997, and 178,100 new cases will be diagnosed, according to the American Cancer Society's Cancer Facts & Figure­p;1997.

-Lorri Preston

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