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New research · Hematology
The Lancet. Oncology · 4d
Randomized trialThe Lancet. Oncology · 2026

Addition of irinotecan to chemoradiotherapy as preoperative treatment for locally advanced rectal cancer (ARISTOTLE): a multicentre, open-label, phase 3, randomised controlled trial.

David Sebag-Montefiore, Richard Adams, Simon Gollins … ARISTOTLE Trial Management Group and Investigators
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HematologyRandomized trial

Irinotecan plus chemoradiotherapy for rectal cancer led to more severe adverse events.

Addition of irinotecan to chemoradiotherapy as preoperative treatment for locally advanced rectal cancer (ARISTOTLE): a multicentre, open-label, phase 3, randomised controlled trial.

David Sebag-Montefiore … ARISTOTLE Trial Management Group and Investigators
The Lancet. Oncology · 2026
Background

Locally advanced rectal cancer is routinely treated with neoadjuvant radiotherapy.

Purpose

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

Were randomly assigned (1:1) to preoperative radiotherapy 45 Gy in 25 daily fractions, combined with either oral capecitabine 900 mg/m 2 alone twice daily on weekdays (standard-of-care group) or oral capecitabine 650 mg/m 2 twice daily on weekdays plus intravenous irinotecan 60 mg/m 2 once weekly in weeks 1-4 (irinotecan group).

n = 589 patients
78%
Results
78%
78% of patients on irinotecan had more severe side effects
n = 589 patients
More results

370 (66%) patients were male, 194 (34%) were female, and median age was 61 years (IQR 54-68); ethnicity data were not collected.

Staging in both groups was similar: 223 (79%) patients in the standard-of-care group and 212 (76%) in the irinotecan group had mrT3 tumours; 44 (15%) and 45 (16%) had mrT4 tumours, respectively.

More results

Patients in the irinotecan group were less likely to receive 45 Gy radiotherapy than in the standard-of-care group (208 [75%] of 276 vs 251 [89%] of 283) or at least 90% of the planned capecitabine dose (187 [68%] of 276 vs 253 [89%] of 283).

“
Conclusion

For MRI-defined, high-risk, locally advanced rectal cancer, the addition of irinotecan to standard of care did not improve outcomes and should not be used in combination with radiotherapy plus capecitabine.

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