O'Shaughnessy J A, Tolcher A, Riseberg D, Venzon D, Zujewski J, Noone M, Gossard M, Danforth D, Jacobson J, Chang V, Goldspiel B, Keegan P, Giusti R, Cowan K H
Medicine Branch, Biostatistics and Data Management Section, National Cancer Institute and Clinical Center, National Institutes of Health, Bethesda, MD USA.
Blood. 1996 Mar 15;87(6):2205-11.
We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAC) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 microg/m2 twice a day subcutaneously, or GM-CSF, 250 microg/m2 daily subcutaneously after FLAC chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/muL for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAC chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAC chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAC chemotherapy and was less well tolerated.
我们进行了一项前瞻性随机试验，以评估白细胞介素-3/粒细胞-巨噬细胞集落刺激因子（GM-CSF）融合蛋白PIXY321与GM-CSF相比，在晚期乳腺癌患者多周期5-氟尿嘧啶、亚叶酸钙、阿霉素、环磷酰胺（FLAC）化疗后改善累积血小板减少症的能力。53例患者被随机分为接受PIXY321，375μg/m²，每日两次皮下注射，或GM-CSF，250μg/m²，在FLAC化疗后每日皮下注射。PIXY321的耐受性不如GM-CSF，有更多患者出现寒战和局部皮肤反应，且更多患者因不耐受而停用PIXY321。虽然两种细胞因子在中性粒细胞最低点方面没有差异，但PIXY321治疗的所有周期中，绝对中性粒细胞计数低于1000/μL的持续时间明显长于GM-CSF。两个研究组中接受多周期FLAC化疗的患者有50%发生了剂量限制性血小板减少症。PIXY321与GM-CSF相比，在血小板最低点、血小板减少持续时间或血小板输注需求方面没有差异。GM-CSF研究组中FLAC化疗的平均给药剂量略高。在改善FLAC化疗多周期观察到的累积血小板减少症方面，PIXY321并不优于GM-CSF，且耐受性较差。
