Lalisang R I, Wils J A, Nortier H W, Burghouts J T, Hupperets P S, Erdkamp F L, Schouten H C, Blijham G H
Department of Internal Medicine, Maastricht University Hospital, The Netherlands.
J Clin Oncol. 1997 Apr;15(4):1367-76. doi: 10.1200/JCO.1997.15.4.1367.
A potential application of hematopoietic growth factors is to obtain an increased dose-intensity. This can be achieved by either higher doses of chemotherapy with standard intervals, or by standard doses with shorter intervals. The potential of these approaches has not been investigated systematically.
In a randomized, multicenter study, 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor (G-CSF) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals (arm one) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide (arm two). A cohort of at least six patients was studied at each interval/dose. A more intensified interval/dose was given if less than 50% of patients encountered a dose-intensity limiting criterium (DILC) in the first three courses.
In arm one, epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic. Subsequently, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC. All initial DILCs consisted of febrile neutropenia. In arm two, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals. In the 10-day interval, eight of 12 patients completed the first three cycles without a DILC. In the 8-day interval, seven of eight patients encountered a DILC. Incomplete neutrophil recovery, and to a lesser extent stomatitis, were dose-limiting.
In combination with G-CSF, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible (projected dose-intensity, 40 mg/m2/wk and 233 mg/m2/wk, respectively). Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days, allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk, respectively.
造血生长因子的一个潜在应用是提高剂量强度。这可以通过以标准间隔给予更高剂量的化疗，或者以更短间隔给予标准剂量来实现。尚未对这些方法的潜力进行系统研究。
在一项随机、多中心研究中，49例晚期乳腺癌患者接受了粒细胞集落刺激因子（G-CSF）治疗，一组患者接受固定间隔增加剂量的表柔比星和环磷酰胺（第一组），另一组患者接受固定剂量的表柔比星和环磷酰胺但间隔逐渐缩短（第二组）。每个间隔/剂量组至少研究6例患者。如果在前三个疗程中少于50%的患者出现剂量强度限制标准（DILC），则给予更高强度的间隔/剂量。
在第一组中，每21天给予表柔比星140mg/m²和环磷酰胺800mg/m²毒性过大。随后，对表柔比星120mg/m²和环磷酰胺700mg/m²进行了测试，10例患者中有2例出现DILC。所有初始DILC均为发热性中性粒细胞减少。在第二组中，表柔比星75mg/m²和环磷酰胺500mg/m²分别以14天和12天的间隔可以安全给药。在10天间隔组中，12例患者中有8例在没有出现DILC的情况下完成了前三个周期。在8天间隔组中，8例患者中有7例出现DILC。中性粒细胞恢复不完全以及程度较轻的口腔炎是剂量限制因素。
与G-CSF联合使用时，每21天给予表柔比星120mg/m²和环磷酰胺700mg/m²是可行的（预计剂量强度分别为40mg/m²/周和233mg/m²/周）。表柔比星75mg/m²和环磷酰胺500mg/m²每10天可以安全给药，预计剂量强度分别为52.5mg/m²/周和350mg/m²/周。
