The clinical development of recombinant human interleukin 11 (NEUMEGA rhIL-11 growth factor)

Completed phase I and II studies of recombinant human interleukin 11 (rhIL-11) demonstrate its potential as a treatment for chemotherapy-induced thrombocytopenia. In a phase I study, 16 women with breast cancer received rhIL-11 (10, 25, 50, 75 or 100 microg/kg s.c. once daily) before and during cycles of moderately dose-intensive chemotherapy. Platelet counts increased in all patients before chemotherapy. During chemotherapy, the mean platelet count nadirs were 67,000 cells/microl (rhIL-11 10 microg/kg) and greater than 150,000 cells/microl (25, 50 and 75 microg/kg). Thus, doses of 25 microg/kg and higher appeared to prevent chemotherapy-induced thrombocytopenia in this study. In a randomized, placebo-controlled study, rhIL-11 (50 microg/kg) prevented the need for platelet transfusions during a subsequent chemotherapy cycle in patients who had already experienced severe chemotherapy-induced thrombocytopenia. Among 82 evaluable patients, 8 (30%) of 27 patients administered rhIL-11 50 microg/kg avoided platelet transfusions versus one (4%) of 28 who received placebo (p < 0.05). rhIL-11-treated patients received approximately two-thirds the number of platelet transfusions that placebo-treated patients received. The median duration of thrombocytopenia (<50,000 cells/microl) was seven days in rhIL-11-treated patients compared to 10 days among patients given placebo. This is the first study in which patients with a history of severe chemotherapy-induced thrombocytopenia who were receiving a variety of chemotherapy regimens have been shown to avoid platelet transfusions following the administration of a thrombopoietic growth factor. This activity of rhIL-11, and the demonstration in preclinical models that it ameliorates chemotherapy-induced mucositis, have promoted its further clinical development as a supportive therapy in patients receiving chemotherapy.