Objective. Our objective was to review oprelvekin, which is a new thrombopoietic cytokine approved in the United States to prevent severe thrombocytopenia and reduce the number of platelet transfusions after myelosuppressive chemotherapy. This article focuses on oprelvekin’s pharmacology, pharmacokinetics, and place in therapy.
Data Sources. A search of the National Cancer Institute-sponsored Cancerlit database from 1963 to 1999 was completed. Subject mesh headings that were searched included interleukin-11, oprelvekin, breast cancer, chemotherapy dose intensity, and cancer pharmacoeconomics. Data were also collected from the package insert and from Genetics Institute (Cambridge, MA) publications.
Study Selection. Searches were limited to studies with humans, which included clinical trials, news articles, and review articles. After reading all of the human clinical trials, additional pertinent citations were obtained and read.
Data Synthesis. Oprelvekin has been studied in both adults and children, with the bulk of the data coming from the treatment of women with breast cancer. A phase I study in adults evaluated doses of 10, 25, 50, 75, and 100 mg/kg/day and determined the maximum tolerated dose to be 50 mg/kg/day. The toxicity seen with the 75 and 100 mg/kg/day doses includes constitutional symptoms (arthralgias, myalgias, fatigue, nausea, and headache) and a cerebral vascular accident. Phase II and III trials showed that 25-50 mg/kg/day effectively reduced the number of patients requiring platelet transfusions and decreased the number of platelet transfusions after chemotherapy.
Pharmacokinetics performed with the 50 mg/kg/day subcutaneous (s.c.) dose resulted in a maximum sera concentration of 17.4 6 5.4 ng/mL, which occurred at 3.2 6 2.4 hours. The terminal half-life was 6.9 6 1.7 hours. Clearance decreases with increasing age, and pediatric patients have a 1.2- to 1.6-fold higher clearance than adults. These pharmacokinetic parameters led to a dosing recommendation of 75- 100 mg/kg/day in pediatric patients.
Due to the high cost of oprelvekin and the lack of data demonstrating that it affects mortality, its role in current therapies is unclear. It is currently being promoted to maintain dose intensity in patients with breast cancer, testicular cancer, and lymphoma. Depending upon institutional platelet and oprelvekin costs, it may also be useful in patients receiving a large number of platelet transfusions. Thus far, it has not demonstrated efficacy in bone marrow transplant patients.
Conclusion. Oprelvekin can effectively prevent the need for platelet transfusion in nontransplant patients receiving myelosuppressive chemotherapy. Due to its high cost, it will most likely be used to maintain chemotherapy dose intensity, which may translate into a survival advantage.
