Shandong First Medical University and Shandong Academy of Medical Sciences Taian, Shandong
X. Dou1, L. Wei2, X. Jiang3, Y. Ding4, S. Sun5, R. Feng1, K. Zhu1, S. Jiang1, F. Shi1, K. Liu6, Y. Sun6, M. Li1, L. N. Zhao7, and J. Yue1; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xian, China, 3Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China, 4Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China, 5Department of Radiation Oncology, Jining Cancer Hospital, Jining, China, 6Department of Colorectal Cancer Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 7Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xian, China
Purpose/Objective(s): Neoadjuvant fluoropyrimidine-based chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard care for locally advanced rectal cancer (LARC). However, this treatment strategy has several limitations, including only 15-20% pathological complete response (pCR) rate, high metastasis rate, and highly inconsistent compliance with adjuvant chemotherapy. Trifluridine/tipiracil (FTD/TPI, TAS-102) is a new oral anti-tumor agent indicated for patients with mCRC who are refractory to standard therapies. The purpose of this study was to investigate the efficacy and safety of TAS-102 concurrent with long-course radiotherapy for patients with LARC. Materials/
Methods: A single-arm, multicenter, phase?trial will recruit 50 LARC patients and all the patients will receive radiotherapy of 50 Gy/25Fx concurrently with TAS-102. TAS-102 will be taken orally twice a day at the 1st, 3rd and 5th week of radiotherapy with dose of 35 mg/m2. After radiotherapy, 2 cycles of consolidation chemotherapy (Oxaliplatin 85 mg/m2 d1+TAS-102 35 mg/m2 bid d1-5, q2w) will be given and the total mesorectal excision (TME) performed within 7-11 weeks. Four cycles of CapeOX (Oxaliplatin 130 mg/m2 d1+ capecitabine 1000 mg/m2 bid d1-14, q3w) after the completion of surgery are optional at the discretion of the treating physicians according to the pathological TNM staging. Results: From September 1, 2022 through January 11, 2024, fifty patients of LARC were enrolled. Up to now, surgery was performed in 39 patients and 11 ones achieved pCR, the pCR rate was 28.2%. Among the patients who did not received surgery, five patients are waiting surgery, one patient achieved cCR and then underwent the watch-and-wait strategy, one patient was confirmed to be MSI-H and dropped out of the study, four patients refused surgery for personal reasons. Grade 3 and 4 toxicities were recorded in 13 (13/50=26%) and 1 (1/50=2%) patients respectively. The commonest grade 3-4 toxicities were leukopenia, neutropenia, and diarrhea, but have no more than grade 3 on hemoglobin and platelet counts. Most patients have no significant gastrointestinal discomfort. Two patients received the reduced dose of TAS-102 due to leukopenia and nausea. Conclusion: Initial results from our study show that TAS-102 concurrent with preoperatively radiotherapy results in a high rate of pCR (28.2%) with acceptable toxicities among patients with stage ?/? rectal cancer. Prospective randomized controlled trial between fluoropyrimidine based and TAS-102 based neoadjuvant chemoradiotherapy are warranted.
