Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, Levy E
J Clin Oncol. 1998 Jan;16(1):301-8. doi: 10.1200/JCO.1998.16.1.301.
The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU.
Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators.
Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)).
5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.
对于晚期结直肠癌患者，持续静脉输注氟尿嘧啶（5-FU）是5-FU推注给药的一种替代方法。尽管已有1200多名患者参加了比较这两种治疗方式的随机试验，但仍没有确凿证据表明5-FU持续静脉输注具有优势，而且这种优势（如果存在的话）的程度也存在争议。进行了一项荟萃分析，以评估在肿瘤反应和生存方面的这种益处，并比较5-FU这两种给药方式的毒性特征。
六项随机试验中纳入的1219例患者的个体数据作为该荟萃分析的基础，该分析由一个独立秘书处与研究人员密切合作进行。
接受5-FU持续静脉输注治疗的患者的肿瘤反应率显著高于接受5-FU推注治疗的患者（22%对14%；总体反应比值比，0.55；95%置信区间[95%CI]，0.41至0.75；P = 0.0002）。接受5-FU持续静脉输注治疗的患者的总生存率也显著更高（总体风险比[HR]，0.88；95%CI，0.78至0.99；P = 0.04），尽管中位生存时间相近。多因素分析表明，随机治疗和体能状态是肿瘤反应仅有的两个显著预测因素，而这两个因素加上原发肿瘤部位是生存的独立显著预测因素（直肠癌患者的情况稍好）。接受5-FU推注治疗的患者3或4级血液学毒性更常见（31%对4%；P < 10⁻¹⁶），而手足综合征在5-FU持续静脉输注组更常见（34%对13%；P < 10⁻⁷）。
在肿瘤反应方面，5-FU持续静脉输注优于5-FU推注，并使总生存率略有提高。接受5-FU持续静脉输注治疗的患者血液学毒性不那么重要，但该组患者手足综合征很常见。
