Wenyang Liu¹, Yu Tang¹, Jing Jin¹, Haizeng Zhang², Lin Yang³, Hua Ren¹,  Hui Fang¹, Weihu Wang¹, Yongwen Song¹, Yueping Liu¹, Shulian Wang¹, Yexiong Li¹

¹Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Science, Beijing, China, ²Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Science, Beijing, China, ³Medical Oncology, Cancer Hospital, Chinese Academy of Medical Science, Beijing, China

Objective:To evaluate the maximum tolerated dose (MTD) of concurrent capecitabine with preoperative radiation (RT) in elderly patients with rectal cancer, as well as safety and efficacy. Method: Surgical candidates aged ≥ 75 years with stage II/III (AJCC 7th) rectal adenocarcinoma were enrolled to receive preoperative concurrent chemoradiation (CRT) with capecitabine. Capecitabine was administered for two cycles of 14 days separated by a 7-day rest, with the dose escalating from 1,000 mg/m²/day as far as no more than 1/3 of patients in a level developing dose limiting toxicities (DLT), to the upper limit at 1,650 mg/m²/d. The academic multidisciplinary team (MDT) then re-evaluated the patients and decided the following treatment within 6-8 weeks after the completion of RT. Result: In the 24 patients enrolled, 17 (70.8%) patients developed grade 2 acute toxicities, while 3 (12.5%) developed grade 3. Radiation dermatitis, gastrointestinal side effects, leukopenia and fatigue were the most common observed acute toxicities. DLTs were seen in one of six patients at each dose level of 1200 mg/m²/d, 1350 mg/m²/d and 1650 mg/m²/d. The MTD was not reached. Only 11 patients underwent surgery, three (27.3%) had pathologic complete response (pCR), and the remaining eight (72.7%) were overall downstaged. No treatment-related death occurred. Three patients (27.3%) had grade 2 or 3 postoperative complications. With a median follow-up of 23 months, the 2-year overall survival rate and 2-year cancer-specific survival rate was 67.4% and 74.9%, respectively. No significant differences were found between the outcomes of patients with or without surgery. Conclusion: In selected elderly patients aged ≥ 75 years with locally advanced rectal cancer, preoperative CRT with capecitabine at the dose of 1650 mg/m²/d was acceptable. Although the pathologic results appeared encouraging, only half of patients received the subsequent surgery, individualized strategy is needed for this fairly old group of patients. (ClinicalTrials.gov number, NCT01584544.).

Key Words: rectal cancer  preoperative concurrent chemoradiotherapy