Results of a phase II trial of short-course radiation and TASOX [trifluridine/tipiracil (TAS-102) plus oxaliplatin] chemotherapy in operable rectal cancer

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Background Trifluridine/tipiracil (FTD/TPI) is approved for metastatic colorectal cancer as monotherapy or in combination with bevacizumab, though dosing in combination with oxaliplatin has not yet been established. The objective of the phase II SHORT trial (NCT04417699) was to determine the efficacy of short-course radiation (SC RT) followed by 3 months of FTD/TPI + oxaliplatin (TASOX) as a condensed total neoadjuvant therapy (TNT) regimen for intermediate-risk rectal cancer. Methods Eligible patients with clinical T3N0 or T1-3N1 nonlow rectal tumors and negative radial tumor margins (>1 mm) were enrolled. The primary endpoint was reduction in neoadjuvant response (NAR) score compared with historic controls. Patients received 25 Gy in five 5 Gy fractions of conformal pelvic radiation followed by six planned 14-day cycles of TASOX: FTD/TPI (35 mg/m 2 /dose) orally b.i.d. day 1-5, oxaliplatin 85 mg/m 2 i.v. day 1. Surgery was recommended within 4 weeks after cycle 6 of TASOX. Results Between 2020 and 2023, 13 patients with stage II ( n = 5) and III ( n = 8) rectal adenocarcinoma were enrolled at three institutions. Dose delivered was 100% of planned radiation, 99% of planned FTD/TPI and 95% oxaliplatin. Diarrhea was documented with a frequency of 11%, and was grade 1 only. Only 9% (8/87) of adverse events were grade 3/4, predominantly related to neutropenia. Among 10 patients who proceeded to total mesorectal excision surgery, 2 experienced a pathological complete response and 2 had a complete clinical response, of which 1 had no evidence of regrowth on continued watch and wait. Conclusions SC RT and 3 months of TASOX can be safely delivered to patients with intermediate-risk rectal cancer, offering a convenient regimen that should be further explored for rectal cancer treatment. The TASOX regimen may be of particular relevance for patients with suspected dihydropyrimidine dehydrogenase deficiency who require oxaliplatin-based therapy.

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