PROSPECTIVE, RANDOMIZED TRIAL OF 5-FLUOROURACIL, LEUCOVORIN, DOXORUBICIN, AND CYCLOPHOSPHAMIDE CHEMOTHERAPY IN COMBINATION WITH THE INTERLEUKIN-3 GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) FUSION PROTEIN (PIXY321) VERSUS GM-CSF IN PATIENTS WITH ADVANCED BREAST-CANCER/

We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (G M-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytope nia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAG) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to r eceive either PIXY321. 375 mu g/m(2) twice a day subcutaneously, or GM -CSF, 250 mu g/m(2) daily subcutaneously after FLAG chemotherapy. PIXY 321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 du e to intolerance. While no difference in the neutrophil nadirs was see n with the two cytokines, the duration of the absolute neutrophil coun t less than 1,000/mu L for all cycles was significantly longer with PI XY321 than with GM-CSF. Fifty percent of patients treated with multipl e cycles of FLAG chemotherapy on both study arms developed dose-limiti ng thrombocytopenia. No differences in platelet nadirs, duration of th rombocytopenia, or need for platelet transfusions were observed with P IXY321 versus GM-CSF. The average delivered doses of FLAG chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superio r to GM-CSF in ameliorating the cumulative thrombocytopenia observed w ith multiple cycles of FLAG chemotherapy and was less well tolerated.