Oprelvekin: a review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia.
Oprelvekin is a recombinant human interleukin-11. Its predominant haemopoietic activity is stimulation of megakaryocytopoiesis. Oprelvekin is indicated for the prevention of severe thrombocytopenia and the reduction of platelet transfusion requirements following myelosuppressive chemotherapy in patients with nonmyeloid malignancies at high risk of severe thrombocytopenia. It is the first available pharmacological alternative to platelet transfusions for these patients. Oprelvekin stimulates platelet progenitor cells (megakaryoblasts and colony-forming unit megakaryocytes). The drug also increases megakaryocyte size and ploidy. The recommended adult dosage of subcutaneous oprelvekin is 50 microg/kg once daily, administered until the platelet count is >or=50 000/microl after the expected nadir, but for not more than 21 days per chemotherapy cycle. Three placebo-controlled trials involving patients with cancer (mostly breast cancer) undergoing dose-intensive cancer chemotherapy, with or without autologous bone marrow transplantation (n = 75 to 82), have been conducted. Compared with placebo, oprelvekin 50 microg/kg/day was associated with significantly fewer patients requiring platelet transfusions and a trend towards a lower median number of platelet transfusions. There was also at least a trend towards reduced time to platelet recovery in oprelvekin recipients. The efficacy of oprelvekin is unaffected by previous platelet transfusion requirements and/or chemotherapy. To date the drug has not been shown to ameliorate chemotherapy-induced leucopenia or neutropenia or to have effects on time to neutrophil engraftment or red blood cell transfusion requirements in clinical trials. The most common adverse events with this agent (oedema and dyspnoea) are considered attributable to drug-induced fluid retention and increased plasma volume; these events are usually mild to moderate, reversible on drug discontinuation and dose related. Cardiovascular events including atrial arrhythmias are also considered attributable to increased plasma volume.


CONCLUSIONS
Evidence suggests that oprelvekin reduces severe thrombocytopenia, accelerates platelet recovery and reduces the need for platelet transfusions in patients with nonmyeloid malignancies receiving chemotherapy regimens associated with severe thrombocytopenia. If further studies confirm these findings, oprelvekin is likely to be a valuable means of allowing patients to receive their full planned chemotherapy course.
Wilde
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Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Faulds
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