Addition of irinotecan to chemoradiotherapy as preoperative treatment for locally advanced rectal cancer (ARISTOTLE): a multicentre, open-label, phase 3, randomised controlled trial
Abstract
Background: Locally advanced rectal cancer is routinely treated with neoadjuvant radiotherapy. Concomitant systemic anticancer therapy with standard fluoropyrimidines has not generally improved outcomes. Small studies reported high pathological complete response rates and acceptable toxicity using irinotecan and fluoropyrimidine chemoradiation. We aimed to explore the effect of the addition of concomitant irinotecan to standard-of-care chemoradiotherapy in patients with locally advanced rectal cancer.
Methods: ARISTOTLE is a multicentre, open-label, parallel-design, phase 3, randomised controlled trial conducted at 75 UK hospital sites treating patients with rectal cancer. Patients were eligible if they were aged at least 18 years with MRI-defined, locally advanced rectal cancer threatening or involving resection margins without metastases. Patients were randomly assigned (1:1) to preoperative radiotherapy 45 Gy in 25 daily fractions, combined with either oral capecitabine 900 mg/m2 alone twice daily on weekdays (standard-of-care group) or oral capecitabine 650 mg/m2 twice daily on weekdays plus intravenous irinotecan 60 mg/m2 once weekly in weeks 1-4 (irinotecan group). Randomisation was done centrally, with allocation concealed to investigators; masking of patients and treating clinicians was not feasible. Stratification was by radiotherapy centre, mesorectal fascia involvement, and presence or absence of equivocal metastatic disease. The primary endpoint was disease-free…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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