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/m(2) of oxaliplatin and 40-60 mg/time of S-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.