Venturini Marco, Del Mastro Lucia, Aitini Enrico, Baldini Editta, Caroti Cinzia, Contu Antonio, Testore Franco, Brema Fulvio, Pronzato Paolo, Cavazzini Giovanna, Sertoli Mario Roberto, Canavese Giuseppe, Rosso Riccardo, Bruzzi Paolo
Institution of Oncologia Medica, Sperimentazioni Cliniche Controllate Istituto Nazionale per la Ricerca sul Cancro, Genova (PB), Italy.
J Natl Cancer Inst. 2005 Dec 7;97(23):1724-33. doi: 10.1093/jnci/dji398.
To determine whether a dose-dense regimen improves outcome in early breast cancer patients, we compared outcomes with the same fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapeutic regimen administered every 3 weeks (FEC21) or administered every 2 weeks (FEC14 including support with filgrastim, a granulocyte colony-stimulating factor) in a multicenter phase III randomized trial.
A total of 1214 patients with early-stage breast cancer were randomly assigned to receive six cycles of FEC14 (604 patients) or of FEC21 (610 patients). Study endpoints were overall survival and event-free survival. Associations were assessed by multivariable analysis with adjustment for age; tumor size; grade; proliferative rate; and menopausal, lymph node, estrogen receptor, and progesterone receptor status. All statistical tests were two-sided.
Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation (26%) than those in the FEC21 arm (33%) (difference = 7%, 95% confidence interval [CI] = 2% to 12%; P = .008). FEC14 therapy, compared with FEC21 therapy, was associated with more asthenia (36% versus 29%, difference = 7%, 95% CI = 2% to 12%; P = .01), bone pain (33% versus 4%, difference = 29%, 95% CI = 25% to 33%; P < .001), anemia (38% versus 19%, difference = 19%, 95% CI = 14% to 24%; P < .001), and thrombocytopenia (8% versus 2%, difference = 6%, 95% CI = 4% to 9%; P < .001), but with less leukopenia (12% versus 45%, difference = 33%, 95% CI = 28% to 37%; P < .001). No acute myelogenous leukemia or myelodysplastic syndrome was observed. At a median follow-up of 10.4 years, no statistically significant difference in the hazard of death (hazard ratio [HR] = 0.87, 95% CI = 0.67 to 1.13) or recurrence (HR = 0.88, 95% CI = 0.71 to 1.08) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis. Although the study was underpowered for subset analysis, we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors.
Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer. However, this therapy was not associated with improved outcome, but because of the limited statistical power of our study, we cannot rule out a modest improvement in outcome associated with FEC14 therapy.
为了确定剂量密集方案是否能改善早期乳腺癌患者的预后，我们在一项多中心III期随机试验中，比较了每3周（FEC21）或每2周（FEC14，包括使用粒细胞集落刺激因子非格司亭支持）给予相同氟尿嘧啶、表柔比星和环磷酰胺（FEC）化疗方案的预后情况。
总共1214例早期乳腺癌患者被随机分配接受6个周期的FEC14（604例患者）或FEC21（610例患者）治疗。研究终点为总生存期和无事件生存期。通过多变量分析评估相关性，并对年龄、肿瘤大小、分级、增殖率以及绝经、淋巴结、雌激素受体和孕激素受体状态进行校正。所有统计检验均为双侧检验。
FEC14组患者出现剂量减少、治疗延迟或中断的情况（26%）少于FEC21组（33%）（差异=7%，95%置信区间[CI]=2%至12%；P=0.008）。与FEC21治疗相比，FEC14治疗与更多的乏力（36%对29%，差异=7%，95%CI=2%至12%；P=0.01）、骨痛（33%对4%，差异=29%，95%CI=25%至33%；P<0.001）、贫血（38%对19%，差异=19%，95%CI=14%至24%；P<0.001）和血小板减少（8%对2%，差异=6%，95%CI=4%至9%；P<0.001）相关，但白细胞减少较少（12%对45%，差异=33%，95%CI=28%至37%；P<0.001）。未观察到急性髓系白血病或骨髓增生异常综合征。中位随访10.4年，多变量分析校正后，FEC14组和FEC21组在死亡风险（风险比[HR]=0.87，95%CI=0.67至1.13）或复发风险（HR=0.88，95%CI=0.71至1.08）方面未发现统计学显著差异。尽管该研究进行亚组分析的效能不足，但我们未发现证据表明治疗类型的效果与任何潜在预后因素相关。
我们的结果支持FEC14化疗作为乳腺癌辅助治疗的长期安全性。然而，这种治疗并未带来预后改善，但由于我们研究的统计效能有限，我们不能排除FEC14治疗与预后有适度改善相关的可能性。
