Abstract：Objective To explore the effectiveness, toxicity and treatment failure patterns for patients with locally advanced rectal adenocarcinoma after pre-operative radiation and concurrent oxaliplatin plus capecitabine. Methods Patients with histopathologically proven rectal adenocarcinoma and clinical stage Ⅱ/Ⅲ were enrolled in a prospective phase Ⅱ clinical trial at 2006—2012 years.One hundred and eighty-six patients received pre-operative chemoradiation,whichconsisted of 44.0—50.4 Gy in 22—28 fractions with concurrent chemotherapy of oral capecitabine 1650 mg/(m2·d) in bid from d1-35 and oxaliplatin 50 mg/m2 per week for 5 times. Radical surgery was performed 4—8 weeks after chemoradiotherapy. Survival rates and multivariate prognostic factors were estimated by Kaplan-Meier method, comparisons were completed by the Log-rank test. Results One hundred and thirty-sevenpatients with clinical stage Ⅱ(n=34) and Ⅲ disease (n=103) underwent radical resection. The lower (the anal distance ≤5 cm) and middle (the anal distance 5—10 cm) located lesions were 102(74.5%) and 35(25.5%), respectively. Diarrhea was the most frequent acute Grade 3 toxicity (n= 29, 21.2%). Sixty-nine patients (50.4%) were downstaged, and21 patients (15.3%) achieved completeregression of primary lesion, 20 patients were pathological comlete response (yp T0N0).With a median follow-up of 22.2 months, the 2-year overall survival, locoregional recurrence free survival and disease free survival for all patients were 92.4%, 93.1% and 71.0%, respectively. In multivariate analysis, pathological stage of yp0—Ⅱ was identified as independent factor related to OS and DFS. Conclusions When delivering oxalipatin plus capecitabine in combination with radiation for locally advanced lower or middle rectal carcinoma, the 2-year locol control was excellent,pathological stage of yp0—Ⅱ was correlated to the favorable survival.
. The effect of oxaliplatin plus capecitabine in combination with radiation for locally advanced lower or middle sited rectal carcinoma[J]. Chinese Journal of Radiation Oncology, 2014, 23(2): 99-103.
[1] NCCN Clinical Practice Guideline in Oncology (NCCN Guidelines) Rectal Cancer Version 4.2013[DB/OL][2014-01-25].http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. [2] Park JH, Yoon SM, Yu CS, et al. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer[J]. Cancer,2011,117:3703-3712. [3] Roh MS, Colangelo LH, O′Connell MJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum:NSABP R-03[J]. J Clin Oncol,2009,27:5124-5130. [4] Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med,2004,351:1731-1740. [5] Gerard JP, Azria D, Gourgou-Bourgade S, et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer:results of the phase Ⅲ trial ACCORD 12/0405-Prodige 2[J]. J Clin Oncol,2010,28:1638-1644. [6] Aschele C, Cionini L, Lonardi S, et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer:pathologic results of the STAR-01 randomized phase Ⅲ trial[J]. J Clin Oncol,2011,29:2773-2780. [7] Rodel C, Liersch T, Becker H, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer:initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial[J]. Lancet Oncol,2012,13:679-687. [8] Gerard JP, Azria D, Gourgou-Bourgade S, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer[J]. J Clin Oncol,2012,30:4558-4565. [9] Roh MS, Yothers GA, O′Connell MJ, et al. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum:NSABP R-04[J]. J Clin Oncol,2011,29 Suppl:abstr 3503. [10] Hans JS, Kim TH, Timothy JP,et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer:first results of the PETACC-6 randomized phase Ⅲ trial[J]. J Clin Oncol,2013,31 Suppl:abstr 3531. [11] Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations[J]. Cancer,1994,73:2680-2686. [12] Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer[J]. N Engl J Med,2006,355:1114-1123. [13] Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer[J]. Br J Surg,2006,93:1215-1223. [14] Gerard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers:results of FFCD 9203[J]. J Clin Oncol,2006,24:4620-4625. [15] Hofheinz RD, Wenz F, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer:a randomised, multicentre, non-inferiority, phase 3 trial[J]. Lancet Oncol,2012,13:579-588. [16] Ngan SY, Burmeister B, Fisher RJ, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer:trans-Tasman Radiation Oncology Group trial 01.04[J]. J Clin Oncol,2012,30:3827-3833. [17] de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer[J]. J Clin Oncol,2000,18:2938-2947. [18] Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage Ⅱ or Ⅲ colon cancer in the MOSAIC trial[J]. J Clin Oncol,2009,27:3109-3116. [19] Collette L, Bosset JF, den Dulk M, et al. Patients with curative resection of cT3—4 rectal cancer after preoperative radiotherapy or radiochemotherapy:does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group[J]. J Clin Oncol,2007,25:4379-4386. [20] Yeo SG, Kim DY, Kim TH, et al. Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer:long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01)[J]. Ann Surg,2010,252:998-1004. [21] Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer:long-term analysis of 566 ypCR patients[J]. Int J Radiat Oncol Biol Phys,2008,72:99-107. [22] Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer[J]. Br J Surg,2012,99:918-928. [23] Lu JY, Xiao Y, Qiu HZ, et al. Clinical outcome of neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine or 5-fluorouracil for locally advanced rectal cancer[J]. J Surg Oncol,2013,108:213-219. [24] Bujko K, Michalski W, Kepka L, et al. Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer:An analysis of outcomes in a randomized trial[J]. Int J Radiat Oncol Biol Phys,2007,67:369-377. [25] Kuo LJ, Liu MC, Jian JJ, et al. Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy[J]? Ann Surg Oncol,2007,14:2766-2772. [26] Quah HM, Chou JF, Gonen M, et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation[J]. Cancer,2008,113:57-64. [27] Seery TE, Ziogas A, Lin BS, et al. Mortality risk after preoperative versus postoperative chemotherapy and radiotherapy in lymph node-positive rectal cancer[J]. J Gastrointest Surg,2013,17:374-381. [28] Bonadeo FA, Vaccaro CA, Benati ML, et al. Rectal cancer:local recurrence after surgery without radiotherapy[J]. Dis Colon Rectum,2001,44:374-379. [29] Holm T, Johansson H, Rutqvist LE, et al. Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer[J]. Br J Surg,2001,88:839-843. [30] Peeters KC, Marijnen CA, Nagtegaal ID, et al. The TME trial after a median follow-up of 6 years:increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma[J]. Ann Surg,2007,246:693-701. [31] Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer[J]. N Engl J Med,2001,345:638-646.
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