Maureen J. Aarts and Vivianne C.G. Tjan-Heijnen, Maastricht University Medical Center, Maastricht; Frank P. Peters, Orbis Medical Center, Sittard-Geleen; Caroline M. Mandigers, Canisius Wilhelmina Hospital; Hanneke W. van Laarhoven and George F. Borm, Radboud University Nijmegen Medical Center; Saskia M. van Gastel; Comprehensive Cancer Centre East; George F. Borm, Nijmegen I, Nijmegen; M. Wouter Dercksen, Maxima Medical Center, Veldhoven; Laurence J. van Warmerdam, Catharina Hospital, Eindhoven; Jacqueline M. Stouthard, Maasstad Medical Center; Carin C. van der Rijt, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam; Hans J. Nortier, Leiden University Medical Center; Erdogan Batman, Diaconessenhuis Leiden, Leiden; Agnes J. van de Wouw, VieCuri Medical Center, Venlo; Esther M. Jacobs, Elkerliek Hospital, Helmond; Vera Mattijssen, Rijnstate Hospital, Arnhem; Tineke J. Smilde, Jeroen Bosch Hospital, 's-Hertogenbosch; Annette W. van der Velden, Martini Hospital, Groningen; Mehmet Temizkan, Hospital St Jansdal, Harderwijk; and Erik W. Muller, Slingeland Hospital, Doetinchem, the Netherlands.
J Clin Oncol. 2013 Dec 1;31(34):4290-6. doi: 10.1200/JCO.2012.44.6229. Epub 2013 Apr 29.
Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy.
In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm.
After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis).
In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.
早期乳腺癌通常采用蒽环类药物和紫杉类药物联合治疗。然而，联合使用这些药物会增加骨髓毒性的风险，可能需要粒细胞集落刺激因子（G-CSF）支持。化疗前两个周期中FN 的发病率最高，G-CSF 的获益最大，这引发了关于在后续化疗周期中继续使用 G-CSF 是否有效的问题。
在一项多中心研究中，选择适合接受三周一次化疗但 FN 风险>20%的乳腺癌患者，随机分配至仅在前两个化疗周期中接受 G-CSF 初级预防（实验组）或所有化疗周期中均接受 G-CSF 初级预防（标准组）。非劣效性假设是，实验组 FN 的发生率将比标准组最多高 7.5%。
纳入 167 例符合条件的患者后，独立数据监测委员会建议提前终止研究。在接受所有化疗周期 G-CSF 治疗的 84 例患者中，有 8 例（10%）发生 FN 事件。相比之下，在仅接受前两个周期 G-CSF 治疗的 83 例患者中，有 30 例（36%）发生 FN 事件（95%CI，0.13 至 0.54），第三个周期（即第一个无 G-CSF 预防周期）的发生率最高，为 24%。
对于 FN 风险高的早期乳腺癌患者，在所有化疗周期中继续使用 G-CSF 初级预防具有临床相关性，因此不能放弃。
