Thrombocytopoenia - eltrombopag
Thrombocytopoenia is a common side-effect of cancer chemotherapy, and is also frequently experienced by patients with a number of other diseases, such as AIDS, chronic liver disease and myelodysplastic syndrome.
Thrombocytopoenia is a common side-effect of cancer chemotherapy, and is also frequently experienced by patients with a number of other diseases, such as AIDS, chronic liver disease and myelodysplastic syndrome.
Normal blood platelet counts are higher than 150,000/µl, but in thrombocytopoenic patients, they may drop below 50,000/µl, leaving the patients prone to bleeding, particularly at the mucous membranes.
The hormone thrombopoetin is produced in the liver, and activates megakaryocytes within the bone marrow so that they turn into platelets. A potential treatment for the condition, therefore, would be to activate these megakaryocytes directly, and a drug with this action, eltrombopag, is being developed by GlaxoSmithKline and Ligand Pharmaceuticals.
In a Phase I clinical trial, 73 healthy male volunteers were given eltrombopag in escalating daily oral doses of 5-75mg or placebo for 10 days.1,2 Its pharmacokinetics were linear, and the drug gave a dose-dependent increase in platelet count. It was well tolerated, with no serious adverse events being experienced, and there were no changes in cardiovascular safety parameters. There was no relationship between the dose and the mostly mild adverse events observed.
A Phase II study has also been carried out, in adult patients with chronic idiopathic thrombocytopenic purpura.3 A total of 104 patients who had been diagnosed at least six months earlier, whose platelet counts were below 30,000/µl and had failed at least one therapy, were given daily oral doses of 30, 50 or 75mg eltrombopag or placebo for six weeks. The primary endpoint was an elevation of platelet count to more than 50,000/µl. While 16% of those given placebo achieved the endpoint, 28%, 67% and 86% of those given the increasing doses did, with the mean platelet count of the 75mg group exceeding 200,000/µl. The most common adverse effect was headache.
It has also been given to patients with hepatitis C related thrombocytopoenia.4 In the Phase II study, subjects were given 30, 50 or 75mg of the drug or placebo for four weeks. Again, no serious adverse events were seen, and 90% of those given the highest dose having their platelet count elevated to above 100,000µl.