Gennari Alessandra, Conte PierFranco, Rosso Riccardo, Orlandini Cinzia, Bruzzi Paolo
Department of Oncology, Division of Medical Oncology, Santa Chiara University Hospital, Pisa, Italy.
Cancer. 2005 Oct 15;104(8):1742-50. doi: 10.1002/cncr.21359.
The expectation of improvement in patient survival with administration of new chemotherapy agents for metastatic breast carcinoma (MBC) is not consistently supported by data from clinical trials, which are often underpowered and have not detected moderate survival advantage. The aim of this study was to evaluate the impact of new agents on prognosis of MBC patients enrolled in clinical trials of first-line chemotherapy.
Between 1983 and 2001, 640 MBC patients were entered into 6 consecutive trials; the present analysis was limited to patients. The date of diagnosis of metastatic breast disease was used to define 5 arbitrarily chosen 3-year time cohorts, 1983-1986, 1987-1989, 1992-1994, 1995-1997, and 1998-2001. Multivariate proportion of hazard (PH) models were used to evaluate changes in overall survival (OS) and progression-free survival (PFS) over time and to detect changes associated with the use of taxanes, while adjusting for differences in baseline factors among 5 cohorts.
Patient characteristics were evenly distributed across the 5 cohorts. Median OS was 18 months, 17.2 months, 19.2 months, 26.1 months, and 23.6 months, respectively, in cohorts 1983-1986, 1987-1989, 1992-1994, 1995-1997, 1998-2001 (P < 0.0001). Age, performance status, relapse-free survival, type of adjuvant treatment, metastatic site, and taxane first-line chemotherapy were all associated with survival. These data failed to provide an indication of temporal trend and suggested a reduction in hazard of death in two cohorts (1995-1997 and 1998-2001) where taxane was added to first-line chemotherapy.
The analysis provided evidence of improvement in prognosis of MBC patients that was associated with use of modern chemotherapeutic agents independent of time.
对于转移性乳腺癌(MBC)患者,使用新型化疗药物有望提高生存率,但临床试验数据并未始终支持这一点,这些试验往往样本量不足,未检测到中等程度的生存优势。本研究的目的是评估新型药物对参加一线化疗临床试验的MBC患者预后的影响。
1983年至2001年间,640例MBC患者参加了6项连续试验;目前的分析仅限于这些患者。转移性乳腺癌的诊断日期用于定义5个任意选择的3年时间队列,即1983 - 1986年、1987 - 1989年、1992 - 1994年、1995 - 1997年和1998 - 2001年。多变量风险比例(PH)模型用于评估总生存期(OS)和无进展生存期(PFS)随时间的变化,并检测与紫杉烷使用相关的变化,同时调整5个队列之间基线因素的差异。
患者特征在5个队列中均匀分布。1983 - 1986年、1987 - 1989年、1992 - 1994年、1995 - 1997年、1998 - 2001年队列的中位OS分别为18个月、17.2个月、19.2个月、26.1个月和23.6个月(P < 0.0001)。年龄、体能状态、无复发生存期、辅助治疗类型、转移部位和紫杉烷一线化疗均与生存相关。这些数据未能显示出时间趋势,提示在一线化疗中添加紫杉烷的两个队列(1995 - 1997年和1998 - 2001年)死亡风险降低。
该分析提供了证据,表明MBC患者的预后改善与使用现代化疗药物相关,且与时间无关。