Jones S E, Schottstaedt M W, Duncan L A, Kirby R L, Good R H, Mennel R G, George T K, Snyder D A, Watkins D L, Denham C A, Hoyes F A, Rubin A S
Texas Oncology, PA, Dallas 75246, USA.
J Clin Oncol. 1996 Nov;14(11):2976-83. doi: 10.1200/JCO.1996.14.11.2976.
To determine the effects of sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the incidence, duration, and complications of myelosuppression after moderate-dose fluorouracil, doxorubicin, cyclophosphamide (FAC) adjuvant chemotherapy in patients with node-positive breast cancer.
In this randomized, double-blind, placebo-controlled study, 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously (IV), doxorubicin 60 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on day 1, followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously (SC) on days 3 through 15. All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count (ANC) was less than 1,000/microL.
Eighty-six percent of GM-CSF patients (n = 62) and 96% of placebo patients (n = 69) completed four assessable cycles of treatment on study. Overall, the median duration of severe neutropenia (ANC < 500/microL) was 2.8 days with GM-CSF and 6.8 days with placebo (P < .001); the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days, respectively (P < .001). Hospitalizations for febrile neutropenia were uncommon in either group: GM-CSF, six; placebo, eight. The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles (P < .001). GM-CSF was generally well tolerated and associated with more injection-site reactions, but less mucositis than placebo. There were no deaths on study.
GM-CSF significantly enhanced ANC recovery after FAC chemotherapy; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined.
确定沙格司亭（重组人粒细胞巨噬细胞集落刺激因子[rhu GM-CSF]）对淋巴结阳性乳腺癌患者在接受中等剂量氟尿嘧啶、多柔比星、环磷酰胺（FAC）辅助化疗后骨髓抑制的发生率、持续时间及并发症的影响。
在这项随机、双盲、安慰剂对照研究中，142例II期和III期乳腺癌女性患者接受4个为期21天的化疗周期，化疗方案为第1天静脉注射氟尿嘧啶600 mg/m²、多柔比星60 mg/m²及环磷酰胺750 mg/m²，随后在第3至15天，安慰剂组患者皮下注射安慰剂，GM-CSF组患者皮下注射GM-CSF 250微克/m²/天。当绝对中性粒细胞计数（ANC）低于1000/微升时，所有患者口服预防性环丙沙星。
GM-CSF组86%（n = 62）的患者和安慰剂组96%（n = 69）的患者完成了研究中的4个可评估治疗周期。总体而言，GM-CSF组严重中性粒细胞减少（ANC < 500/微升）的中位持续时间为2.8天，安慰剂组为6.8天（P < .001）；ANC低于1000/微升的持续时间分别为6.0天和9.1天（P < .001）。两组因发热性中性粒细胞减少住院的情况均不常见：GM-CSF组6例，安慰剂组8例。血液学毒性方面的唯一其他差异是，在第3和第4周期中，GM-CSF组患者3/4级血小板减少的发生率高于安慰剂组。GM-CSF提高了完成两个或更多周期治疗患者的FAC平均剂量强度（P < .001）。GM-CSF总体耐受性良好，注射部位反应较多，但黏膜炎比安慰剂组少。研究期间无死亡病例。
GM-CSF显著促进了FAC化疗后ANC的恢复；降低了相关中性粒细胞减少症的发生率和持续时间，并适度提高了辅助化疗的剂量强度。这些效果最终是否会转化为长期预后的改善仍有待确定。
