Magazine article Drug Topics

TPO Agents Poised to Reduce Platelet Transfusions

Magazine article Drug Topics

TPO Agents Poised to Reduce Platelet Transfusions

Article excerpt

Bleeding disorders caused by low platelet counts are seen frequently in patients undergoing rigorous cancer chemotherapy or in those who have received a bone marrow transplant. There are other causes also.

The solution has been to give the patient platelet transfusions. Because they come from donor blood, however, such transfusions bring their own problems. Now, the cloning of several groups of thrombopoietin (TPO), a substance that stimulates the formation of platelets, has raised the hope that the number of platelet transfusions can be reduced.

One such agent is a recombinant megakaryocyte growth and development factor (rMGDF) developed by Amgen. A recombinant TPO by Genentech has also entered the clinical arena.

At the annual meeting of the American Society of Clinical Oncology in Philadelphia, investigators updated the audience on clinical studies using these platelet growth factors. Steven Bernstein, M.D., of the Roswell Park Cancer Institute, Buffalo, described why such a product is needed especially for patients undergoing marrow or peripheral blood stem cell transplants.

"Despite recent advances in cytokine and stem cell technology, platelet transfusions are not yet a thing of the past," he said, in a report for the Platelet Recovery Study Group and Genentech.

Bernstein reported that an observational study of platelet utilization at 18 U.S. and Canadian transplant centers in 789 evaluable patients indicated that yearly costs of platelet transfusions would conservatively run more than $100 million for transplant patients alone, without taking into consideration the cost of the management of transfusions and hemorrhagerelated complications for such patients.

Reporting for a multicenter study group that took the unusual step of conducting a phase I/II trial that was randomized, double-blind, and placebocontrolled, Michael Paul Fanucci, M.D., Emory School of Medicine, Atlanta, found that the use of Amgen pegylated rMGDF resulted in a dose-related improvement in the time it took for the platelet count to rebound to baseline values seen prior to chemotherapy in 53 patients with advanced nonsmall-cell lung cancer. The platelet nadir, or lowest point, was also 70% higher in patients getting the recombinant MGDF at all the doses tested, compared with those who got placebo, he said.

Although this was only a phase I/II trial, 19 patients of the 42 available for tumor response assessment showed a partial response to their treatment. Side effects, he said, included thrombocytosis at the highest doses. One patient developed a deep vein thrombosis and a pulmonary embolism in the presence of a normal platelet count; this resolved with heparin. …

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