The phase I trial of preoperative short-course chemoradiotherapy with S-1/irinotecan and short-course radiation in locally advanced lower rectal cancer (SHOWTIME study)

Sep 22, 2026

A phase I clinical study evaluated irinotecan dosing within short-course chemoradiotherapy using S-1/irinotecan and short-course radiotherapy for locally advanced lower rectal cancer. The trial determined maximum tolerated dose and recommended dose based on dose-limiting toxicity assessed over 14 days. Fifteen patients completed the protocol; diarrhea was the most common Grade ≥3 adverse event. At 60 mg/m² DLT occurred in all, while 50 mg/m² established the recommended dose, with high R0 resection and favorable downstaging.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Background

Trial rationale and TNT context

Methods

Dosing schedule and radiotherapy regimen

Results

DLT, adverse events, and surgical outcomes

Conclusion

Kojo etal. Radiation Oncology (2026) 21:109 Radiation Oncology [https://doi.org/10.1186/s13014-026-02872-3](https://doi.org/10.1186/s13014-026-02872-3) RESEARCH Open Access The phase I trial of preoperative short-course chemoradiotherapy with S-1/irinotecan and short-course radiation in locally advanced lower rectal cancer (SHOWTIME study) Ken Kojo 1*, Toshimichi Tanaka1, Takahiro Yamanashi1, Hirohisa Miura1, Keigo Yokoi1, Keita Kojima 1, Kazuko Yokota1, Shogo Kawakami2, Hiromichi Ishiyama2, Keishi Yamashita3, Yusuke Kumamoto4, Naoki Hiki5, Takeo Sato6 and Takeshi Naitoh 1 Abstract Background A phase I study was conducted to determine the optimal dose of irinotecan in short-course chemoradiotherapy (SCCRT) using S-1/irinotecan and short-course radiotherapy (SCRT) for the development of anew total neoadjuvant therapy (TNT) regimen that is safe, effective, and has a low patient burden for locally advanced rectal cancer (LARC) . Methods The objective of this study was to ascertain the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan in SCCRT for locally advanced rectal cancer. The assessment of dose-limiting toxicity (DLT) was conducted over a 14-day period following treatment administration. The patient received a 14-day course of chemotherapy, with S-1 administered from the first to the fifth day and from the eighth to the twelfth day. Irinotecan was administered on the first and eighth days of treatment. The radiotherapy regimen was initiated with a total dose of 25 Gy, administered in five fractions from the eighth to twelfth day. Results Fifteen patients received SCRT in conjunction with S-1 and escalating doses of irinotecan (40–60 mg/m²) . All patients completed the SCCRT protocol. At a dose of 60 mg/m², DLT occurred in all patients, thereby establishing this dosage as the MTD. At a dose of 50 mg/m², DLT was observed in two of six patients, thereby establishing this dose asthe RD. The most prevalent Grade ≥3 adverse event was diarrhea. All patients received CapeOX-based consolidation chemotherapy. Among the 11 surgical cases, the R0 resection rate was 100%, with a pathological complete response in 27 . 3% and downstaging in 90. 9% . Three patients demonstrated a complete clinical response and underwent nonoperative management. Conclusion The safety and feasibility of administering SCCRT with S-1/irinotecan at a 50 mg/m² irinotecan dose have been demonstrated. These findings support further investigation of this regimen in a TNT setting for rectal cancer. *Correspondence: Ken Kojo[kkojo@kitasato-u.ac.jp](kkojo@kitasato-u.ac.jp) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Kojo et al. Radiation Oncology (2026) 21:109 Page 2 of 9 Trial registration The present study was duly registered with the Japan Clinical Trials Registry (jRCT s031210461) . URL: [https://jrct.mhlw.go.jp/re](https://jrct.mhlw.go.jp/re). Keywords Advanced rectal cancer, Chemoradiotherapy, Total neoadjuvant therapy Background

FAQs

What was the primary goal of the phase I SHOWTIME study?

To determine the maximum tolerated dose and the recommended dose of irinotecan in short-course chemoradiotherapy (SCCRT) for locally advanced lower rectal cancer.

How was dose-limiting toxicity assessed in the trial?

Dose-limiting toxicity was evaluated during a 14-day period after treatment administration.

Which dose level was selected as the recommended dose, and why?

The recommended dose was 50 mg/m² because DLT occurred in 2 of 6 patients at this level, while 60 mg/m² caused DLT in all patients and was the MTD.

Sep 22, 2026

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