Scinto A F, Ferraresi V, Campioni N, Tonachella R, Piarulli L, Sacchi I, Giannarelli D, Cognetti F
Servizio di Oncologia Medica, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy.
Ann Oncol. 1995 Sep;6(7):665-71. doi: 10.1093/oxfordjournals.annonc.a059282.
This study evaluated the toxicity of high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeks and compared the dose-intensity achieved with this schedule with that obtained in a previous study we conducted in which the same regimen was given every 3 weeks without G-SCF (EC 21). The secondary objective was to explore the activity of this regimen.
Between December 1991 and March 1994, 41 patients (pts), 19 with locally advanced breast cancer (LABC) and 22 with metastatic breast cancer (MBC), were given high-dose epirubicin (Hd-Epi) (120 mg/m2) and cyclophosphamide (CTX) (600 mg/m2) on day 1 every 14 days (EC 14) plus granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/d s.c. on days 2-12). A total of 8 cycles in LABC pts (4 pre- and post-surgery), and 6-8 cycles in MCB pts were administered. The results were compared with those obtained in the previous study.
The incidence of WHO grade 3-4 neutropenia was significantly reduced in the EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214 and 250 evaluable cycles, respectively, p<0.0001), as well as the incidence of neutropenic fever (7% vs. 3%, p=0.05). Grade 3-4 anemia (36.6% vs. 8% pts, p=0.001) and grade 3-4 thrombocytopenia (17.1% vs. 0 pts, p=0.002), were significantly more frequent in EC 14 + G-CSF. No significant differences in the other side effects were found. A total of 17 of 207 of the cycles (8.2%) were delayed in the EC 14 + G-CSF vs. 58/271 (21.4%) in the EC 21 (p<0.0001). The main reasons for these treatment delays were neutropenia (1% vs. 15%), anemia (3% vs. 0) and thrombocytopenia (1% vs. 0). As a result of treatment acceleration and differences in dose delays, the patients on EC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m2/wk vs. 36.8 mg/m2/wk; CTX 292.52 mg/m2/wk vs. 182.9 mg/m2/wk). A complete response at surgery was obtained in 9/19 (47.4%) LABC pts. An objective CR was obtained in 11/22 MBC pts (50%) and a partial response in 8/22 (36.4%), yielding an overall response rate of 86.4%.
Hd-Epi + CTX is very active against both LABC and MBC. The administration of G-CSF allows dose intensification of both drugs (a 59.5% increase of the actual dose intensity) with acceptable clinical tolerance (a lower incidence of neutropenia but a higher incidence of anemia and thrombocytopenia). Only a specifically designed phase III trial will lead to definitive conclusions regarding the greater antitumor activity of accelerated CSF-including regimens as compared to standard chemotherapy for advanced breast cancer.
本研究评估了每2周给予高剂量表柔比星、环磷酰胺加r-met-HUG-CSF（G-CSF）的毒性，并将该方案的剂量强度与我们之前进行的一项研究（每3周给予相同方案但不加G-SCF，即EC 21）所获得的剂量强度进行比较。次要目的是探索该方案的活性。
1991年12月至1994年3月，41例患者，19例局部晚期乳腺癌（LABC）患者和22例转移性乳腺癌（MBC）患者，每14天（EC 14）的第1天给予高剂量表柔比星（Hd-Epi）（120 mg/m²）和环磷酰胺（CTX）（600 mg/m²），加粒细胞集落刺激因子（G-CSF）（第2 - 12天皮下注射5 mcg/kg/d）。LABC患者共给予8个周期（手术前后各4个周期），MBC患者给予6 - 8个周期。将结果与之前研究所得结果进行比较。
EC 14 + G-CSF方案中WHO 3 - 4级中性粒细胞减少的发生率显著降低（在214个和250个可评估周期中分别为25.2%和46.8%，p<0.0001），中性粒细胞减少性发热的发生率也降低（7%对3%，p = 0.05）。EC 14 + G-CSF方案中3 - 4级贫血（36.6%对8%患者，p = 0.001）和3 - 4级血小板减少（17.1%对0例患者，p = 0.002）显著更常见。在其他副作用方面未发现显著差异。EC 14 + G-CSF方案中207个周期中有17个（8.2%）延迟，而EC 21方案中271个周期中有58个（21.4%）延迟（p<0.0001）。这些治疗延迟的主要原因是中性粒细胞减少（1%对15%）、贫血（
