Fanucchi M, Glaspy J, Crawford J, Garst J, Figlin R, Sheridan W, Menchaca D, Tomita D, Ozer H, Harker L
Department of Medicine, and the Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
N Engl J Med. 1997 Feb 6;336(6):404-9. doi: 10.1056/NEJM199702063360603.
Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy.
We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given.
In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base-line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis.
MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.
聚乙二醇（PEG）偶联的重组人巨核细胞生长和发育因子（MGDF，也称为PEG-rHuMGDF），一种与血小板生成素相关的重组分子，可特异性刺激巨核细胞生成和血小板产生，并降低接受骨髓抑制性化疗动物的血小板减少症严重程度。
我们对53例接受卡铂和紫杉醇治疗的肺癌患者进行了一项关于MGDF的随机、双盲、安慰剂对照剂量递增研究。患者按4人一组以1:3的比例随机分配，接受皮下注射安慰剂或MGDF（每天每千克体重0.03、0.1、0.3、1.0、3.0或5.0微克）。未给予其他骨髓活性细胞因子。
在化疗后接受MGDF的38例患者中，血小板计数最低点的中位数为每立方毫米188,000（范围为68,000至373,000），而接受安慰剂的12例患者中为每立方毫米111,000（范围为21,000至307,000）（P = 0.013）。治疗患者的血小板计数在14天内恢复至基线水平，而接受安慰剂的患者则超过21天（P<0.001）。在所有40例接受MGDF治疗的患者中，1例发生深静脉血栓形成和肺栓塞，另1例发生浅表血栓性静脉炎。
MGDF对化疗诱导的血小板减少症患者的血小板生成具有强大的刺激作用。
