Gray Richard, Barnwell Jennifer, McConkey Christopher, Hills Robert K, Williams Norman S, Kerr David J
Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.
Lancet. 2007 Dec 15;370(9604):2020-9. doi: 10.1016/S0140-6736(07)61866-2.
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/m2) 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% CI 1.0-6.0).
背景：QUASAR试验的目的是确定辅助化疗对复发风险低的结直肠癌患者的生存获益大小及持续时间，此类患者的化疗指征尚不清楚。 方法：1994年5月至2003年12月期间，来自19个国家150个中心的3239例患者（2963例[91%]为II期[无淋巴结转移]疾病，2291例[71%]为结肠癌，中位年龄63岁[四分位间距56 - 68岁]）在接受了看似根治性的结肠癌或直肠癌切除术后，被随机分配接受氟尿嘧啶和亚叶酸钙化疗（n = 1622）或观察（复发时考虑化疗；n = 1617）。化疗方案为每4周进行6个为期5天的疗程，或30个每周一次的静脉注射氟尿嘧啶（370mg/m²）加用高剂量（175mg）L - 亚叶酸钙或低剂量（25mg）L - 亚叶酸钙的疗程。1997年前，加用左旋咪唑（每3天450mg，共12个疗程，每2周重复）或安慰剂。1997年后，分配接受化疗的患者仅给予氟尿嘧啶和低剂量亚叶酸钙。主要结局为全因死亡率。分析采用意向性治疗。本试验已在国际临床试验注册中心注册，注册号为ISRCTN82375386。 结果：分析时，化疗组有61例（3.8%）患者、观察组有50例（3.1%）患者失访。中位随访5.5年（范围0 - 10.6年）后，化疗组有311例死亡，观察组有370例死亡；化疗组与单纯观察组相比，任何原因导致的死亡相对风险为0.82（95%CI 0.70 - 0.95；p = 0.008）。化疗组有293例复发，观察组有359例复发；化疗组与单纯观察组相比，复发相对风险为0.78（0.67 - 0.91；p = 0.001）。治疗疗效在肿瘤部位、分期、性别、年龄或化疗方案方面无显著差异。化疗组有8例（0.5%）患者、观察组有4例（0.25%）患者在随机分组后30周内死于非结直肠癌原因；其中仅1例死亡被认为可能与化疗有关。 解读：氟尿嘧啶和亚叶酸钙化疗可改善II期结直肠癌患者的生存，尽管绝对改善幅度较小：假设无化疗时5年死亡率为20%，此处观察到的死亡相对风险转化为生存绝对改善率为3.6%（95%CI 1.0 - 6.0）。
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