重组人血小板生成素治疗实体肿瘤患者化疗后血小板减少的多中心临床试验

目的评价国产重组人血小板生成素(rhTPO)治疗实体肿瘤患者化疗后血小板减少的临床疗效和安全性.方法采用随机交叉自身对照研究,154例实体瘤患者随机分为A、B两组,每组77例,接受方案和剂量相同的两周期化疗.A组:第1个周期(用药周期)注射rhTPO,第二个周期(对照周期)不注射rhTPO;B组:第1个周期(对照周期)不注射rhTPO,第2个周期(用药周期)注射rhTPO.两组患者均于用药周期化疗结束后6～24 h皮下注射rhTPO 1.0μg·kg-1·d-1,连续用药最长14 d.监测血尿便常规、肝肾功能、凝血功能、胸片、心电图及血清抗rhTPO抗体.结果A、B两组用药周期与对照周期血小板减少程度和持续时间差异无显著性.154例实体瘤患者用药周期与对照周期比较:(1)化疗后血小板下降的最低值分别为(64.4±45.4)×109/L和(52.4±30.9)×109/L(P=0.000),血小板计数恢复后的最高值分别为(263.9±142.5)×109/L和(148.9±67.7)×109/L(P=0.000);(2)化疗后血小板＜50×109/L的持续时间分别为(2.5±3.9)和(3.7±5.7)d(P=0.04);(3)用药周期化疗后血小板恢复至75×109/L、100×10 9/L以上所需天数为(10.3±8.7)和(14.0±8.9)d,而对照周期为(15.9±10.5)和(21.1±9.5)d(P=0.000);(4)血小板平均输注量两周期比较无差异;(5)化疗后血红蛋白、白细胞、尿常规、便常规、肝肾功能、凝血功能、胸片和心电图的变化无明显差异.1例患者产生低滴度非中和性血清抗rhTPO抗体.不良反应轻,仅个别患者出现发热、头晕或寒战.结论实体肿瘤患者化疗后给予国产rhTPO可减少血小板降低程度和持续时间,并能促进血小板恢复,且无严重不良反应.

A multi-center clinical trial of recombinant human thrombopoietin in the treatment of chemotherapy-induced thrombocytopenia in patients with solid tumor

OBJECTIVE: To assess the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in patients with solid tumor. METHODS: In this randomized crossover self-controlled multi-center clinical trial, 154 patients with solid tumor were randomly divided into two groups (group A 77 cases and group B 77 cases). All patients were given the same two cycles of chemotherapy. In group A, the first cycle was treated cycle, in which patients were given rhTPO, while the second cycle was non-treated cycle as a control. In group B, the first cycle was non-treated cycle as a control, while the second cycle was treated cycle. RhTPO 1.0 microg/(kg x d) was administered subcutaneously 6-24 hours after chemotherapy for the longest 14 days. Laboratory tests included complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiogram. Serum samples were screened for anti-rhTPO antibodies. RESULTS: In both group A and group B, platelet decrease and duration had no significant difference between the treated cycle and non-treated cycle. Platelet count was higher in the treated cycle, than in the non-treated cycle: minimal mean platelet count (64.4 +/- 45.4) x 10(9) cells/L and (52.4 +/- 30.9) x 10(9) cells/L (P=0.000), maximal mean platelet count (263.9 +/- 142.5) x 10(9) cells/L and (148.9 +/- 67.7) x 10(9) cells/L (P=0.000)]. Duration of thrombocytopenia was shorter in the treated cycle than in the non-treated cycle days with platelet count < 50 x 10(9) cells/L, (2.5 +/- 3.9) and (3.7 +/- 5.7) (P=0.04); days with platelet count recovered > or = 75 x 10(9) cells/L, (10.3 +/- 8.7) and (14.0 +/- 8.9) (P=0.000), and days with platelet count recovered > or = 100 x 10(9) cells/L, (15.9 +/- 10.5) and (21.1 +/- 9.5) (P=0.000)]. The need for platelet transfusion was not significantly reduced in treated cycle. The effects of rhTPO on WBC, Hb, hepatic function, renal function, and coagulant function were not found. Transient low-titer non-neutralizing antibody was developed in one patient. Therapy with rhTPO was tolerated by all patients. Mild side effects were observed in individual patients, including fever, dizziness, and chill. Conclusion Administration of rhTPO after chemotherapy can significantly reduce the degree and duration of thrombocytopenia and promote platelet recovery. Therapy with rhTPO seems to be safe.