Safety and Efficacy of SOX Therapy After Preoperative Chemoradiotherapy for Advanced Lower Rectal Cancer - A Phase I Study

Sep 23, 2026

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Phase I study evaluated S-1 plus oxaliplatin (SOX) as consolidation chemotherapy after chemoradiotherapy (CRT) within total neoadjuvant therapy (TNT) for locally advanced lower rectal cancer. Patients with stage II/III lower rectal adenocarcinoma received long-course CRT followed by two SOX cycles using a 3+3 dose-escalation design. Dose-limiting toxicity in cycle 1 identified the recommended oxaliplatin 130 mg/m² and S-1 40–60 mg/time; grade ≥3 leukopenia and neutropenia occurred at dose level 2 only. Surgery was performed as planned; pathological complete response was 8.3%.

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CategoryHealthcare

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Abstract

Background/Aim

Patients and Methods

Results

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Introduction

Patients and Methods

doi: 10.21873/invivo.14307 Safety and Efficacy of SOX Therapy After Preoperative Chemoradiotherapy for Advanced Lower Rectal Cancer: A Phase I Study MANABU YAMAMOTO, KEI URAKAMI, KOTAROOSAKI, CHIHARU YASUI, TAKUKIYAGYU, YUSUKE KONO, KYOICHI KIHARA, TOMOYUKI MATSUNAGA, NARUO TOKUYASU, SHUICHI TAKANO, TERUHISA SAKAMOTO and YOSHIYUKI FUJIWARA Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago, Japan Abstract Background/Aim: This phase 1 study aimed to evaluate the safety and tolerability of S-1 plus oxaliplatin (SOX) as consolidation chemotherapy following chemoradiotherapy (CRT) in total neoadjuvant therapy (TNT) for locally advanced lower rectal cancer. Patients and Methods: Patients with stage II/III lower rectal adenocarcinoma received long-course CRT followed by two cycles of SOX therapy. A standard 3+3 dose-escalation design was used to determine the recommended dose. The primary endpoint was the incidence of dose-limiting toxicity (DLT) during the first chemotherapy cycle. Secondary endpoints comprised pathological complete response, adverse events, treatment completion, and surgical outcomes. Results: The DLT was evaluated in 12 patients. One DLT was observed at dose level 1, while no DLTs were observed at dose level 2. This established the recommended dose as 130 mg/m² of oxaliplatin and 40-60 mg/time ofS-1 (based on body surface area) . Grade 3 hematologic toxicities (leukopenia, neutropenia) occurred in three patients at dose level 2; there were no non-hematologic adverse events with a grade ≥3 . Twelve patients underwent surgery within the planned timeframe. Among these 12 patients, one achieved a pathological complete response (8.3%) and one experienced a postoperative complication of Clavien-Dindo grade ≥2 . Conclusion: SOX therapy as consolidation chemotherapy after CRT was safe and well tolerated as part of the TNT for lower rectal cancer. To our knowledge, this is the first study to report the use of SOX in TNT. Further trials are warranted to evaluate the efficacy of SOX as consolidation therapy after CRT in larger populations. Keywords: Rectal cancer, SOX, total neoadjuvant therapy. Manabu Yamamoto, Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School Univamorosi@ttyoFttaocrui-ltyuoacfjMpedicine, 36-1 Nishi-cho, Yonago 683-8504, Japan. Tel: +81 859386567, Fax: +81 Received January 10, 2026 | Revised March 7, 2026 | Accepted March 10, 2026 of Medicine, Tottori 859386569, e-mail: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ©2026 The Author(s) . Anticancer Research is published by the International Institute of Anticancer Research. Introduction Colorectal cancer (CRC) remains one of the most common cancers worldwide. Despite advancesin surgical techniques and the development of molecularly targeted therapies and immune checkpoint inhibitors, CRC continues to be the second leading cause of cancer-related death globally (1). Due to its anatomical location within the narrow pelvis, rectal cancer presents unique surgical challenges and has a significantly higher rate of local recurrence compared with colon cancer (2, 3). In particular, lower rectal cancer is associated with a greater incidence of distant metastases and poorer overall survival (OS) and disease-free survival (DFS) compared with tumors located in the upper or middle rectum (4, 5). Therefore, it is critical to control both local recurrence and distant metastases in the management of advanced lower rectal cancer. In Western countries, preoperative chemoradiotherapy (CRT) followed by total mesorectal excision has been established asthe standard treatment for locally advanced rectal cancer, primarily owing to its efficacy in reducing local recurr

FAQs

What treatment strategy did the phase 1 study evaluate for locally advanced lower rectal cancer?

It evaluated SOX (S-1 plus oxaliplatin) as consolidation chemotherapy after preoperative chemoradiotherapy, as part of total neoadjuvant therapy (TNT).

What was the primary endpoint of the study?

The primary endpoint was the incidence of dose-limiting toxicity (DLT) during the first chemotherapy cycle.

What recommended dose was established for SOX therapy?

The recommended dose was oxaliplatin 130 mg/m² plus S-1 40–60 mg/time based on body surface area.

Sep 23, 2026

Uploaded by Stanley