Safety and Tolerability of Different Total Neoadjuvant Therapies in Patients With Locally Advanced Rectal Cancer.

BACKGROUND

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer (LARC). Few studies have focused on the toxicity of TNT. Moreover, the differences in safety and tolerability between radiotherapy-first and chemotherapy-first strategies remain unclear. This study aimed to evaluate the differences in treatment-related toxicities between radiotherapy-first and chemotherapy-first strategies for TNT in patients with LARC.

METHODS

Patients with LARC who were treated with TNT at a single cancer center between June 2020 and July 2023 were retrospectively included. TNT consisted of induction chemotherapy followed by long-course chemoradiotherapy (INCT-LC-CRT) or long-course chemoradiotherapy/short-course radiotherapy followed by consolidation chemotherapy (LC-CRT-CNCT/SC-RT-CNCT). Adverse events (AEs) and treatment exposure were compared between the groups.

RESULTS

Overall, 93 patients were included. Patients in the INCT-LC-CRT and LC-CRT-CNCT/SC-RT-CNCT groups were 28 (30.1%) and 45 (48.4%) / 20 (21.5%), respectively. Chemotherapy-related grade 3 or 4 AEs were significantly more frequent in the LC-CRT-CNCT/SC-RT-CNCT group than in the INCT-LC-CRT group (50.8% vs. 17.9%, p < 0.01) but were not significantly different between the LC-CRT-CNCT and SC-RT-CNCT groups (53.3% vs. 40.0%, p = 0.42). The proportion of patients who received a full dose of chemotherapy was higher in the INCT-LC-CRT group than in the LC-CRT-CNCT/SC-RT-CNCT group (53.6% vs. 24.6%; p < 0.01). One (3.6%) and six (9.2%) patients discontinued chemotherapy owing to AEs in the INCT-LC-CRT and LC-CRT-CNCT/SC-RT-CNCT groups, respectively.

CONCLUSIONS

Grade 3 or 4 AEs during chemotherapy were more frequent and required dose modification in the LC-CRT-CNCT/SC-RT-CNCT group than in the INCT-LC-CRT group.