{"id":9500,"date":"2025-12-02T10:10:50","date_gmt":"2025-12-02T10:10:50","guid":{"rendered":"https:\/\/www.library.sath.nhs.uk\/research\/?p=9500"},"modified":"2025-12-02T10:10:51","modified_gmt":"2025-12-02T10:10:51","slug":"aristotle-mature-results-of-a-phase-3-trial-evaluating-the-addition-of-irinotecan-to-capecitabine-chemoradiation-in-locally-advanced-rectal-cancer-2025","status":"publish","type":"post","link":"https:\/\/www.library.sath.nhs.uk\/research\/2025\/12\/02\/aristotle-mature-results-of-a-phase-3-trial-evaluating-the-addition-of-irinotecan-to-capecitabine-chemoradiation-in-locally-advanced-rectal-cancer-2025\/","title":{"rendered":"ARISTOTLE: Mature results of a phase 3 trial evaluating the addition of irinotecan to capecitabine chemoradiation in locally advanced rectal cancer (2025)"},"content":{"rendered":"\n<p><strong>Type of publication:<\/strong><\/p>\n\n\n\n<p>Conference abstract<\/p>\n\n\n\n<p><strong>Author(s):<\/strong><\/p>\n\n\n\n<p>Sebag-Montefiore D.; Samuel L.; *Gollins S.; Glynne-Jones R.; Harte R.; West N.; Quirke P.; Myint A.S.; Bach S.; Falk S.; Parsons P.; Dhadda A.; Misra V.; Brown G.; Harrison M.; White L.; Duggan M.; Begum R.; Chang E.; Musleh R.; Lopes A.; Adams R.<\/p>\n\n\n\n<p><strong>Citation:<\/strong><\/p>\n\n\n\n<p>Radiotherapy and Oncology. Conference: ESTRO 2025. Vienna Austria. 206(Supplement 1) (pp S1192-S1194), 2025. Date of Publication: 01 May 2025<\/p>\n\n\n\n<p><strong>Abstract:<\/strong><\/p>\n\n\n\n<p>Purpose\/Objective: To determine if the addition of irinotecan to capecitabine chemoradiation (CRT) improves disease-free survival in MRI-defined locally advanced rectal cancer (LARC). Material\/Methods: ARISTOTLE (ISRCTN:09351447) is a phase III, multi-centre, open-label trial that randomly assigned (1:1) patients with MRI-defined LARC threatening or involving resection margins without metastases to pre-operative radiotherapy:45Gy\/25 fractions combined with either capecitabine 900mg\/m<sup>2<\/sup> (CRT) or 650 mg\/m<sup>2<\/sup> bd weekdays with Irinotecan iv once-weekly 60mg\/m<sup>2<\/sup> (IrCRT) weeks 1-4. The primary endpoint is disease-free survival (DFS). Result(s): 75 UK sites randomised 564 eligible patients from 10\/2011 to 07\/2018; 284 to CRT and 280 to IrCRT. 66% male; median age 61 years (range:24-83). Radiological staging in both arms was similar:mrT3(77%), mrT4(16%); mrCRM involved(49%);resection margin threatened &lt;=1mm(38%). Median follow-up is 62.1 months.Compared with CRT, IrCRT patients were less likely to receive 45Gy RT: 208(75%) vs 251(89%), p &lt; 0.001; or receive >=90% capecitabine dose:187(68%) in IrCRT vs 253(89%) CRT, p &lt; 0.001. 205(74%) IrCRT patients received >=90% irinotecan dose. >=Gd 3 non-haematological adverse events included fatigue 17(6%) vs 8(3%) p=0.06; diarrhoea:14% vs 4% p&lt;0.001; abdominal pain 5% vs &lt;1% p=0.001 for IrCRT and CRT respectively. >=Gd 3 haematological adverse events included leucopaenia: 9% vs 2%, p&lt;0.001; neutropaenia: 10% vs 1%,p&lt;0.001; and febrile neutropaenia: 1% vs &lt;1% for IrCRT and CRT respectively. 5 patients had a grade 5 adverse event (3 lrCRT,2 CRT). The median time from the end of RT to surgery was 10.6 weeks. 238(85%) and 243(86%) patients underwent surgery in the IrCRT and CRT arms. The R0 resection rate was 90% vs 89% p=0.75 for IrCRT and CRT respectively. The pCR rate was 20% for IrCRT vs 18% for CRT p = 0.52. The rate of any post-surgical complications was similar in both arms:94(39%) for IrCRT and 91(37%) for CRT p=0.65). There is no evidence of a difference in loco-regional failure free (HR 0.94 [0.46-1.90]p=0.86, distant metastasis free (HR 0.89 [0.63-1.25] p=0.51), disease free HR 0.87 [0.64-1.18] p=0.37) or overall survival (HR 0.91[0.63-1.30],p=0.59) when IrCRT is compared with CRT. Conclusion(s): For patients with MRI-defined high risk LARC, low rates of CRM involvement and 36 month loco-regional failure were observed.The addition of irinotecan to CRT was associated with decreased radiotherapy and chemotherapy compliance and a higher rate of adverse events.There is no evidence of a difference in the pCR rate,36 month locoregional recurrence free or disease-free survival.<\/p>\n\n\n\n<p><strong>DOI:&nbsp;<\/strong>10.1016\/S0167-8140%2825%2900901-6<\/p>\n\n\n\n<p>Link to full-text<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Type of publication: Conference abstract Author(s): Sebag-Montefiore D.; Samuel L.; *Gollins S.; Glynne-Jones R.; Harte R.; West N.; Quirke P.; Myint A.S.; Bach S.; Falk S.; Parsons P.; Dhadda A.; Misra V.; Brown G.; Harrison M.; White L.; Duggan M.;<span class=\"ellipsis\">&hellip;<\/span><\/p>\n<div class=\"read-more\"><a href=\"https:\/\/www.library.sath.nhs.uk\/research\/2025\/12\/02\/aristotle-mature-results-of-a-phase-3-trial-evaluating-the-addition-of-irinotecan-to-capecitabine-chemoradiation-in-locally-advanced-rectal-cancer-2025\/\">Read more <span class=\"screen-reader-text\">ARISTOTLE: Mature results of a phase 3 trial evaluating the addition of irinotecan to capecitabine chemoradiation in locally advanced rectal cancer (2025)<\/span><span class=\"meta-nav\"> &#8250;<\/span><\/a><\/div>\n<p><!-- end of .read-more --><\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"content-type":"","footnotes":""},"categories":[200],"tags":[1085,758,353],"class_list":["post-9500","post","type-post","status-publish","format-standard","hentry","category-staff-publication","tag-1085","tag-chemoradiotherapy","tag-oncology"],"_links":{"self":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/9500","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/comments?post=9500"}],"version-history":[{"count":1,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/9500\/revisions"}],"predecessor-version":[{"id":9501,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/posts\/9500\/revisions\/9501"}],"wp:attachment":[{"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/media?parent=9500"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/categories?post=9500"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.library.sath.nhs.uk\/research\/wp-json\/wp\/v2\/tags?post=9500"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}