EFFECT OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ON CHEMOTHERAPY-INDUCED MYELOSUPPRESSION
EFFECT OF RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ON CHEMOTHERAPY-INDUCED MYELOSUPPRESSION
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DOI：
10.1056/nejm198809083191001
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发表时间：
1988-09-08
影响因子：
158.5
通讯作者：
SCHNIPPER, LE
中科院分区：
文献类型：
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作者：
ANTMAN, KS;GRIFFIN, JD;SCHNIPPER, LE
化疗剂量的增加增强了许多实验和临床癌症的反应，但剂量增加的程度往往受到骨髓抑制的限制。在初步试验中，重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)可以增加白细胞数量和功能，但最佳剂量尚未确定。我们对16例无法手术或转移肉瘤的成年人进行治疗，在第一周期化疗(周期1)之前和之后立即递增剂量的重组人粒细胞集落刺激因子，以评估血液学反应和毒性。第二周期化疗(周期2)不含重组人粒细胞集落刺激因子。在每天每公斤体重4-32微克剂量下，重组人粒细胞集落刺激因子耐受性良好。在每天每公斤体重的剂量下，四名患者中有两名出现中心静脉导管周围的水肿和血栓。在输注重组人GM-CSF的过程中，白细胞和粒细胞计数显著升高。周期1后中性粒细胞减少的严重程度和持续时间明显低于周期2(P<；0.01)。平均白细胞总数和血小板最低值分别为1.0倍和101倍。第一周期为每升109次，0.45和44次。化疗第1天至中性粒细胞恢复的中位时间间隔(>；0.500倍)。每升109天)分别为15天和19天(P<；0.01)。第1周期中性粒细胞减少时间为3.5d，第2周期为7.4d(P<；0.01)。我们的结论是，在每天每公斤32微克的剂量下，重组人粒细胞集落刺激因子耐受性良好，并且在白细胞减少患者中具有生物学活性。在预防化疗并发症方面值得进一步评价。
An increase in the dose of chemotherapy enhances the response of many experimental and clinical cancers, but the extent of dose escalation is often limited by myelosuppression. In preliminary trials, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has augmented leukocyte numbers and function, but the optimal dose is not established. We treated 16 adults who had inoperable or metastatic sarcomas with escalating doses of rhGM-CSF before and immediately after a first cycle of chemotherapy (cycle 1) to assess hematologic response and toxicity. A second cycle of chemotherapy (cycle 2) was given without rhGM-CSF. RhGM-CSF was tolerated well at doses of 4 to 32 .mu.g per kilogram of body weight per day. At 64 .mu.g per kilogram per day, edema and thrombi around a central venous catheter developed in two of four patients. Leukocyte and granulocyte counts increased significantly during the rhGM-CSF infusion. Neutropenia after cycle 1 was significantly less severe and shorter in duration than after cycle 2 (P < 0.01). Mean total leukocyte and platelet nadirs were 1.0 and 101 .times. 109 per liter for cycle 1 and 0.45 and 44 .times. 109 per liter for cycle 2 (P < 0.01), and the median intervals from day 1 of chemotherapy to neutrophil recovery (> 0.500 .times. 109 per liter) were 15 and 19 days, respectively (P < 0.01). The duration of neutropenia was 3.5 days with cycle 1 and 7.4 days with cycle 2 (P < 0.01). We conclude that rhGM-CSF is tolerated well at doses up to 32 .mu.g per kilogram per day and is biologically active in leukopenic patients. It merits further evaluation for the prevention of morbidity from chemotherapy.