Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study
- PMID: 18083404
- DOI: 10.1016/S0140-6736(07)61866-2
Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study
Abstract
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).
Comment in
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Adjuvant chemotherapy of colorectal cancer.Lancet. 2007 Dec 15;370(9604):1980-1. doi: 10.1016/S0140-6736(07)61841-8. Lancet. 2007. PMID: 18083386 No abstract available.
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Adjuvant chemotherapy for rectal cancer.Lancet. 2008 May 3;371(9623):1502-3; author reply 1503. doi: 10.1016/S0140-6736(08)60650-9. Lancet. 2008. PMID: 18456096 No abstract available.
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Adjuvant chemotherapy increased survival in colorectal cancer patients with low recurrence risk.ACP J Club. 2008 May 20;148(3):6. ACP J Club. 2008. PMID: 18489069 No abstract available.
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Is adjuvant therapy for stage II colon cancer worthwhile, and for whom?Nat Clin Pract Gastroenterol Hepatol. 2008 Aug;5(8):422-3. doi: 10.1038/ncpgasthep1181. Epub 2008 Jul 1. Nat Clin Pract Gastroenterol Hepatol. 2008. PMID: 18594496 No abstract available.
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