Pre-operative bevacizumab, capecitabine and radiation among patients with locally advanced rectal cancer

doi:10.3969/j.issn.1009-976X.2015.03.004

Abstract

Abstract: 【Abstract】〓Objective〓To evaluate the safety and efficacy of pre-operative chemoradiation, using capecitabine and bevacizumab with standard doses of radiation, in patients with locally advanced rectal cancer. Methods〓Patients with locally advanced cancer were treated with capecitabine 825 mg/m2 twice daily on days 1-14 and bevacizumab 5 mg/kg on days 14, 1, 15 and 29, and radiation 50.4 Gy in 28 fractions including boost.Total mesorectal excision was performed 7-9 weeks after chemoradiation. Results〓Forty-two evaluable patients were enrolled, and 38 proceeded to definitive surgery. Eighteen patients (43%) had clinical T4 tumours and/or N2 tumours. Mean relative dose intensity was >90% for all systemic agents, and 97% for radiation. Grade 3/4 diarrhoea occurred in 10 patients (24%) and pain in 4 patients (10%) pre-operatively, while grade 3/4 pain, fatigue and infection were each reported among 5 patients (13%) post-operatively. Re-operation due to complications occurred in 4 patients (11%). Complete tumour regression (ypT0) was seen in 9 patients (23.7%) of which 2 had N1 disease (5.3%) and the pathological complete response (pCR) rate (ypT0N0) was 18.4%. Conclusion〓In this study, pre-operative bevacizumab added to capecitabine and radiation was safe and resulted in a promising tumour regression rate.

Key words: Bevacizumab, Capecitabine, Radiotherapy, Locally advanced rectal cancer

摘要： 【摘要】〓目的〓评价局部进展期直肠癌患者术前应用贝伐单抗联合卡培他滨化疗以及标准剂量放疗的效果和安全性。方法〓选择局部进展直肠癌患者应用卡培他滨825 mg/m2、2次/d,第1~14 d和22~35天;贝伐单抗5 mg/kg,放疗前第14 d,放疗后1、15、29 d;放疗50.4Gy分28次。放化疗7~9周后实施TME手术。结果〓纳入42例可评估患者,其中38例手术,18例(43%)临床T4和/或N2,平均相对强度>90%,97%照射。术前组10例(24%)发生3/4级腹泻,4例(10%)出现疼痛,而术后组的5例(13%)患者均出现3/4级疼痛、乏力和感染,4例(11%)因出现并发症再次手术。术后38例中肿瘤完全消退达T0 的有9例(9/38,23.7%);其中达T0N0 7例(7/38,18.4%)、T0N1 2例(5.3%)。结论〓本研究提示术前贝伐单抗联合卡培他滨和放疗在期望肿瘤衰退率方面是安全和有效的。

关键词: 贝伐单抗, 卡培他滨, 放射治疗, 局部进展期直肠癌

CLC Number:

R657.1

Wang Dongxia, Li Yuechun, Sun Yanqiu, Zhao Zhengjun, Zhao Yanhai, Li Xianming. Pre-operative bevacizumab, capecitabine and radiation among patients with locally advanced rectal cancer[J]. Lingnan Modern Clinics in Surgery, 2015, 15(03): 256-260.

王东霞李月春孙彦秋赵正军赵艳海李先明. 术前贝伐单抗联合卡培他滨及放疗在局部进展期直肠癌中的应用研究[J]. 岭南现代临床外科, 2015, 15(03): 256-260.

References

[1]Ferlay J, Shin HR, Bray F, et al.Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008[J].Int J Cancer, 2010, 127(12):2893-2917 [2] Tepper JE, O’Connell M, Niedzwiecki D, et al.Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control–final report of intergroup 0114[J].J Clin Oncol, 2002, 20(7):1744-1750 [3] Smalley SR, Benedetti JK, Williamson SK, et al.Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144[J].J Clin Oncol, 2006, 24(22):3542-3547 [4] R?del C, Liersch T, Hermann RM, et al.Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer [J].J Clin Oncol, 2007, 25(1):110-117 [5] Ryan DP, Niedzwiecki D, Hollis D, et al.Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: cancer and leukemia group B 89901[J].J Clin Oncol, 2006, 24(16):2557-2562 [6] Hurwitz H, Fehrenbacher L, Novotny W, et al.Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer[J].N Engl J Med, 2004, 350(23):2335-2342 [7] Dworak O, Keilholz L, Hoffmann A.Pathological features of rectal cancer after preoperative radiochemotherapy[J].Int J Colorectal Dis, 1997, 12(1):19-23 [8] Bujko K, Nowacki MP, Kepka L, et al.Postoperative complications in patients irradiated pre-operatively for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs chemoradiation[J].Colorectal Dis, 2005, 7(4):410-416 [9] Gérard 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].Clin Oncol, 2010, 28(10):1638-1644 [10] Fernández-Martos C, Pericay C, Aparicio J, et al.Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study[J].J Clin Oncol, 2010, 28(5):859-865 [11] Bosset JF, Collette L, Calais G, et al.Chemotherapy with preoperative radiotherapy in rectal cancer[J].N Engl J Med, 2006, 355(7):1114-1123 [12] Bosset JF, Calais G, Mineur L, et al.Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results–EORTC 22921[J]. . 2005，23(24)5620–5627.[J].J Clin Oncol, 2005, 23(24):5620-5627 [13] McCahill LE, Yothers G, Sharif S, et al.Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically unresectable metastatic colon cancer and an intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10[J].J Clin Oncol, 2012, 30(26):3223-3228 [14] Willett CG, Boucher Y, di Tomaso E, et al.Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer[J].Nat Med, 2004, 10(2):145-147