Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study
Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study
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DOI：
10.1016/s0140-6736(07)61866-2
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发表时间：
2007-12-15
期刊：
影响因子：
168.9
通讯作者：
Kerr, David J.
中科院分区：
文献类型：
--
作者：
Gray, Richard;Barnwell, Jennifer;Kerr, David J.
QUASAR试验的目的是确定辅助化疗对低复发风险的结直肠癌患者的生存获益的大小和持续时间，这些患者的适应症尚不清楚。方法1994年5月至2003年12月，来自19个国家150个中心的3239例结肠癌或直肠癌切除后明显治愈的患者（II期[淋巴结阴性]2963例[91%]，结肠癌2291例[71%]，中位年龄63 [IQR 56-68]岁），随机分为氟尿嘧啶和亚叶酸化疗组（n=1622）和观察组（考虑化疗是否复发，n=1617）。化疗分为6个疗程，每4周5天，或30个疗程，每周1次，静脉注射氟尿嘧啶（370 mg/m(2)），高剂量（175 mg） l -亚叶酸或低剂量（25 mg） l -亚叶酸。直到1997年，左旋咪唑（每2周重复一次，每次450毫克，3天，12个疗程）或安慰剂被添加。1997年以后，指定接受化疗的患者只给予氟尿嘧啶和低剂量亚叶酸。主要结局为全因死亡率。分析是按照意向进行的。该试验已在国际临床试验注册中心注册，编号为ISRCTN82375386。分析时，化疗组61例（3.8%）患者和观察组50例（3.1%）患者未随访。中位随访5.5年（0 ~ 10.6年）后，化疗组311例死亡，观察组370例死亡；化疗与单独观察相比，任何原因死亡的相对风险为0.82 （95% CI 0.70-0.95; p=0.008）。化疗组复发293例，观察组复发359例；化疗与单独观察的相对复发风险为0.78 （0.67-0.91;p=0.001）。治疗效果没有因肿瘤部位、分期、性别、年龄或化疗方案而有显著差异。化疗组8例（0.5%）患者和观察组4例（0.25%）患者在随机分组的30周内死于非结直肠癌；这些死亡中只有一人被认为可能与化疗有关。氟尿嘧啶和亚叶酸联合化疗可以改善II期结直肠癌患者的生存，尽管绝对改善很小：假设无化疗的5年死亡率为20%，此处所见的相对死亡风险转化为生存的绝对改善为3.6% （95% Cl 1.0-6.0）。
Background The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant Chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear.Methods After apparently curative resections of colon or rectal cancer, 3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m(2)) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386.Findings At the time of analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the observation group had missing follow-up. After a median follow-up of 5.5 (range 0-10.6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy schedule. Eight (0.5%) patients in the chemotherapy group and four (0.25%) in the observation group died from non-colorectal cancer causes within 30 weeks of randomisation; only one of these deaths was deemed to be possibly chemotherapy related.Interpretation Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer, although the absolute improvements are small: assuming 5-year mortality without chemotherapy is 20%, the relative risk of death seen here translates into an absolute improvement in survival of 3.6% (95% Cl 1.0-6.0).