QUASAR: A randomized study of adjuvant chemotherapy (CT) vs observation including 3238 colorectal cancer patients.
Gray RG., Barnwell J., Hills R., McConkey C., Williams N., Kerr D., QUASAR Collaborative Group None.
3501 Background: The size of survival benefit from adjuvant fluorouracil/folinic acid (FUFA) CT for colorectal cancer is unclear. METHODS: Patients with apparently curative resections of colon or rectal cancer were randomized following surgery between FUFA and observation (with CT considered on recurrence). CT consisted of either six 5-day, four-weekly or 30 once-weekly courses of intravenous fluorouracil (370mg/m(2)) with either high-dose (175mg) or low-dose (25mg) L-folinic acid, and with either levamisole or placebo. Primary outcome was all cause mortality. RESULTS: Between June 1994 and December 2003, 3238 patients (91% Dukes B, 71% colon cancer, median age 63) from 150 centres in 17 countries were randomised. Direct randomised comparisons found no benefit for high-dose FA or levamisole (Lancet 2000;355:1588-1596). A non-randomised comparison suggested equal efficacy but less toxicity with the once-weekly schedule (Annals of Oncology 2000;11:947-955). With a median follow-up of 4.2 years, risk of death with CT vs control was 0.88 (95%CI 0.75-1.05; p=0.15) and recurrence 0.82 (0.70-0-97; p=0.02). Treatment efficacy did not differ significantly by stage, site or age but efficacy of the 4-weekly schedule was significantly (p=0.04) greater than once-weekly -a prior hypothesis. CONCLUSIONS: Chemotherapy produces a small (1% - 5%) survival benefit for stage B patients, sufficient to outweigh the inconvenience and cost for high-risk and younger patients. Longer follow-up and meta-analysis of all trials is needed to clarify the balance of benefits and disbenefits for older patients. No significant financial relationships to disclose.