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

Purposes: 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-ll (rhIL-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/m(2)) and doxorubicin (75 mg/m(2)) plus granulocyte colony-stimulating factor (G-CSF; 5 mu g/kg/d). patients were randomized to blinded treatment with placebo or 50 mu g/kg/d rhIL-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, rhIL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhIL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P=.04). Treatment with rhIL-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/mu L in the second cycle (P =.01), Most adverse events associated with rhIL-11 were reversible, mild to moderate in severity, and likely related to fluid retention. Conclusions: rhIL-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. (C) 1997 by American Society of Clinical Oncology.