Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin

Purpose: Thrombocytopenia may compromise cancer treatment, causing chemotherapy dose reductions, schedule alterations, or the need for platelet transfusions. We evaluated the efficacy and safety of recombinant human interleukin-11 (rhlL-11; Neumega, Genetics Institute, Inc, Cambridge, MA), a novel thrombopoietic growth factor, in reducing the need for platelet transfusions in patients who undergo dose-intensive chemotherapy. Patients and Methods: Women with advanced breast cancer received cyclophosphamide (3,200 mg/m²) and doxorubicin (75 mg/m²) plus granulocyte colony- stimulating factor (G-CSF; 5 μg/kg/d). Patients were randomized to blinded treatment with placebo or 50μg/kg/d rhlL-11 subcutaneously for 10 or 17 days after the first two chemotherapy cycles. Results: Seventy-seven patients were randomized and constitute the intent-to-treat (ITT) population. Sixty-seven patients (the assessable subgroup) either completed both cycles without a major protocol violation (n = 62) or received a platelet transfusion before treatment was discontinued after the first cycle. In the ITT population, rhlL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhlL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P = .04). Treatment with rhlL-11 significantly reduced the total number of platelet transfusions required in the assessable subgroup (P = .03) and the time to platelet recovery to more than 50,000/ μL in the second cycle (P = .01). Most adverse events associated with rhlL-11 were reversible, mild to moderate in severity, and likely related to fluid retention. Conclusion: rhlL-11 is safe and effective in reducing treatment-associated thrombocytopenia and the need for platelet transfusions in patients who undergo dose-intensive chemotherapy, and thus may permit chemotherapy to be administered as planned at intended doses and thereby maximize the potential for a successful outcome.