Aglietta M, Monzeglio C, Pasquino P, Carnino F, Stern A C, Gavosto F
Clinica Medica dell'Università, Novara, Italy.
Cancer. 1993 Nov 15;72(10):2970-3. doi: 10.1002/1097-0142(19931115)72:10<2970::aid-cncr2820721018>3.0.co;2-0.
Administration of granulocyte-macrophage colony stimulating factor (GM-CSF) is followed by a rapid increase in the proliferative activity of the hematopoietic precursors. Within 72 hours after its suspension, however, establishment of a negative feedback results in a reduction of the proliferative activity of the hyperplastic marrow to values below the baseline, suggesting refractoriness of hematopoietic progenitors to the action of cell-cycle-specific cytostatic agents.
The hypothesis that short treatment with GM-CSF before chemotherapy could reduce the hematopoietic toxicity of cytostatics was investigated by administering GM-CSF glycosylate (Sandoz, Basel, Switzerland/Schering-Plough, Kenilworth, NJ) subcutaneously with a 5.5 micrograms/kg protein dosage per day from day-6-day-4 before each course of adjuvant chemotherapy (cyclophosphamide, epirubicin, 5-fluorouracil/cyclophosphamide, methotrexate, 5-fluorouracil alternate) in patients with node-positive breast cancer. Twelve patients were randomized to receive GM-CSF before chemotherapy or only at chemotherapy. The hematologic picture and dose intensity of chemotherapy were compared in the two groups of patients.
In the group of patients receiving chemotherapy only, 22% of the cycles had to be postponed because of leukopenia, with a consequent reduction of the dose intensity, whereas in the GM-CSF group, the neutrophil counts remained at significantly (P < 0.001) higher levels, and there were no delays in chemotherapy administration. No substantial systemic toxicity was associated with this brief GM-CSF schedule. Moreover, GM-CSF treatment did not result in delayed depletion of the hematopoietic pool.
Short treatment with GM-CSF can enable the dose intensity of conventional protocols of proven efficacy to be increased.
给予粒细胞-巨噬细胞集落刺激因子（GM-CSF）后，造血前体细胞的增殖活性迅速增加。然而，在其停用后72小时内，负反馈机制的建立导致增生骨髓的增殖活性降至基线以下，提示造血祖细胞对细胞周期特异性细胞抑制剂的作用产生了耐药性。
通过在辅助化疗（环磷酰胺、表柔比星、5-氟尿嘧啶/环磷酰胺、甲氨蝶呤、5-氟尿嘧啶交替使用）的每个疗程前6天至4天，以每天5.5微克/千克蛋白质的剂量皮下注射糖基化GM-CSF（瑞士巴塞尔山德士公司/美国新泽西州肯尼沃思先灵葆雅公司），研究GM-CSF在化疗前短期治疗能否降低细胞抑制剂的造血毒性这一假设。12例淋巴结阳性乳腺癌患者被随机分为化疗前接受GM-CSF组或仅在化疗时接受GM-CSF组。比较两组患者的血液学情况和化疗的剂量强度。
仅接受化疗的患者组中，22%的化疗周期因白细胞减少而不得不推迟，导致剂量强度降低；而在GM-CSF组中，中性粒细胞计数显著（P<0.001）维持在较高水平，化疗给药未出现延迟。这种短期GM-CSF给药方案未伴有明显的全身毒性。此外，GM-CSF治疗未导致造血池的延迟耗竭。
GM-CSF短期治疗可提高已证实有效的传统方案的剂量强度。
