Addition of irinotecan to chemoradiotherapy as preoperative treatment for locally advanced rectal cancer…

Randomized trialThe Lancet. Oncology· Aug 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

HematologyRandomized trialTreatmentQ1IF 9.4

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 · Aug 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.

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

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

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