Impact of neoadjuvant chemotherapy following chemoradiation on tumor response, adverse events, and surgical complications in patients with advanced rectal cancer treated with TME.

Abstract

3514 Background: A pathologic complete response (pCR) to pre-operative chemoradiation (CRT) is associated with improved prognosis in rectal cancer patients treated with total mesorectal excision (TME), but the proportion of patients who achieve a pCR is relatively small. We investigated the effect of adding increasing cycles of pre-operative neoadjuvant chemotherapy after CRT followed by surgery on pCR rate, adverse events (AEs) and surgical complications. Methods: Three sequential phase II trials or study groups (SGs) were conducted in patients with endorectal ultrasound or MRI Stage II and III rectal cancer. All patients were treated with neoadjuvant 5-FU-based CRT, followed by 0, 2 or 4 cycles of mFOLFOX-6 followed by TME. Tumor response was assessed by pathology according to RECIST criteria. AEs and surgical complications were reported according to CTCAE 3.0. Results: Demographics were similar between SGs. Clinical characteristics, treatment compliance, pathological tumor response, AEs and surgical complications are shown below (Table). Conclusions: Advanced rectal cancer patients who receive pre-operative CRT and increasing cycles of chemotherapy before surgery have a higher pCR rate without increasing AEs or surgical complications. Studies assessing delivering all chemotherapy before rather than after TME are underway. SG1 n=60 SG2 n=67 SG3τ n=48 Clinical stage II 19 (32%) 12 (18%) 13 (27%) III 41 (68%) 55 (82%) 35 (73%) Treatment compliance CRT 44 (73%) 53 (79%) 42 (88%) mFOLFOX-6 --- 58 (87%) 41 (85%) Median CRT-to-surgery timeÔ 40 77 106 R0 resection 58 (97%) 64 (96%) 32 (97%)* Sphincter saving surgery 46 (77%) 50 (75%) 38 (79%) Temporary ileostomy 38 (63%) 43 (64%) 38 (79%) Nodes examined 13±7 15±7 14±7 Pelvic fibrosis† 2.4±1.7 4.0±2.6 4.1±2.4 Surgical difficultyψ 4.5±2.7 5.1±2.7 4.9±2.6 Tumor response pCR 11 (18%) 17 (25%) 15 (31%) pPR 43 (72%) 50 (75%) 32 (67%) Stable disease 6 (10%) 0 (0%) 1 (2%) Grade 3+ AEs 26 (43%) 23 (34%) 19 (40%) Grade 3+ surgical complications 9 (15%) 4 (6%) 5 (12%)** Based on 33* and 42** patients; ÔDays; †1=none-10=max; ψ1=easy-10=difficult; τ60 patients accrued, 48-surgery; pPR: pathologic partial response.