Efficacy and safety of consolidation chemotherapy during the resting period in patients with local advanced rectal cancer

Liang,Huan‑Qing; Dong,Zhong‑Yi; Liu,Zhi‑Jie; Luo,Jiao; Zeng,Qin; Liao,Ping‑Yan; Wu,De‑Hua

doi:10.3892/ol.2018.9804

Efficacy and safety of consolidation chemotherapy during the resting period in patients with local advanced rectal cancer

Authors:
- Huan‑Qing Liang
- Zhong‑Yi Dong
- Zhi‑Jie Liu
- Jiao Luo
- Qin Zeng
- Ping‑Yan Liao
- De‑Hua Wu
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Affiliations: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Radiation Oncology, Cancer Institute of Guangxi Zhuang Autonomous Region, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: December 6, 2018 https://doi.org/10.3892/ol.2018.9804
Pages: 1655-1663
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

It remains controversial as to whether a long interval between neoadjuvant chemoradiotherapy (NCRT) and surgery may provide clinical benefits for patients with local advanced rectal cancer (LARC). The addition of consolidation chemotherapy during the resting period was recently considered as a treatment option. The present study aimed to verify the efficacy and safety of consolidation chemotherapy during the resting period in patients with LARC. A total of 156 patients with local advanced stage T3‑4N0‑2 rectal cancer were enrolled between January 2010 and July 2016. Patients were divided into two groups, those who received consolidation chemotherapy prior to surgery (n=76) and the control group who did not (n=80). Multivariate logistic regression and the Kaplan‑Meier method were used to explore the predictors of pathological complete response (pCR) and survival. The demographic and tumor characteristics were comparable between the two groups. The consolidation group yielded significantly higher pCR and near pCR rates compared with the control group (P=0.015). Patients in the consolidation group who also underwent standard adjuvant chemotherapy displayed improved 3‑year disease‑free survival (DFS) compared with the control group (P=0.036). Notably, the addition of consolidation chemotherapy between NCRT and surgery did not significantly increase the incidence of surgical complications and grade 3 or 4 toxicities when compared with the control group. Consolidation chemotherapy was associated with increased pCR/near pCR rates and improved 3‑year DFS, and displayed a manageable safety profile. The present study provided primary evidence for the efficacy and safety of consolidation chemotherapy in LARC. Further prospective studies are warranted in the future to verify these results.

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1	Bray F, Sankila R, Ferlay J and Parkin DM: Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer. 38:99–166. 2002. View Article : Google Scholar : PubMed/NCBI
2	Heald RJ, Husband EM and Ryall RD: The mesorectum in rectal cancer surgery-the clue to pelvic recurrence? Br J Surg. 69:613–616. 1982. View Article : Google Scholar : PubMed/NCBI
3	Havenga K, Enker WE, Norstein J, Moriya Y, Heald RJ, van Houwelingen HC and van de Velde CJ: Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: An international analysis of 1,411 patients. Eur J Surg Oncol. 25:368–374. 1999. View Article : Google Scholar : PubMed/NCBI
4	Benson AB, Venook AP, Cederquist L, Chan E, Chen YJ, Cooper HS, Deming D, Engstrom PF, Enzinger PC, Fichera A and Grem JL: Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. J Natl Comp Cancer Network. 15:370–398. 2017. View Article : Google Scholar
5	Chua YJ: Pathological complete response: Still a relevant endpoint in rectal cancer? The Lancet Oncology. 11:807–808. 2010. View Article : Google Scholar : PubMed/NCBI
6	Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, et al: Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: A pooled analysis of individual patient data. Lancet Oncol. 11:835–844. 2010. View Article : Google Scholar : PubMed/NCBI
7	Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, Souquet JC, Adeleine P and Gerard JP: Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: The Lyon R90-01 Randomized Trial. J Clin Oncol. 17:23961999. View Article : Google Scholar : PubMed/NCBI
8	Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, et al: Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: A multicentre, phase 2 trial. Lancet Oncol. 16:957–966. 2015. View Article : Google Scholar : PubMed/NCBI
9	Tulchinsky H, Shmueli E, Figer A, Klausner JM and Rabau M: An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol. 15:2661–2667. 2008. View Article : Google Scholar : PubMed/NCBI
10	Swellengrebel HA, Bosch SL, Cats A, Vincent AD, Dewit LG, Verwaal VJ, Nagtegaal ID and Marijnen CA: Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: A near pathologic complete response does not translate into good clinical outcome. Radiother Oncol. 112:44–51. 2014. View Article : Google Scholar : PubMed/NCBI
11	Wolthuis AM, Penninckx F, Haustermans K, De Hertogh G, Fieuws S, Van Cutsem E and D'Hoore A: Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 19:2833–2841. 2012. View Article : Google Scholar : PubMed/NCBI
12	Habr-Gama A, Perez RO, Proscurshim I, Nunes Dos Santos RM, Kiss D, Gama-Rodrigues J and Cecconello I: Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: Does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys. 71:1181–1188. 2008. View Article : Google Scholar : PubMed/NCBI
13	Supiot S, Bennouna J, Rio E, Meurette G, Bardet E, Buecher B, Dravet F, Le Neel JC, Douillard JY, Mahé MA and Lehur PA: Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer. Colorectal Dis. 8:430–435. 2006. View Article : Google Scholar : PubMed/NCBI
14	Edge SB and Compton CC: The american joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
15	Moore HG, Gittleman AE, Minsky BD, Wong D, Paty PB, Weiser M, Temple L, Saltz L, Shia J, Shia J and Guillem JG: Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum. 47:279–286. 2004. View Article : Google Scholar : PubMed/NCBI
16	Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, et al: Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 29:3753–3760. 2011. View Article : Google Scholar : PubMed/NCBI
17	Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, et al: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 351:1731–1740. 2004. View Article : Google Scholar : PubMed/NCBI
18	Cienfuegos JA, Baixauli J, Pastor C, Arredondo J, Sola JJ, Arbea L, Chopitea A and Hernandez-Lizoain JL: Long-term oncologic results in cancer of the rectum treated by preoperative chemoradiotherapy and surgery: An analysis of 500 cases. Rev Esp Enferm Dig. 107:340–346. 2015.PubMed/NCBI
19	Lima IS, Yasui Y, Scarfe A and Winget M: Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada. Cancer. 117:3833–3840. 2011. View Article : Google Scholar : PubMed/NCBI
20	Tevis SE, Kohlnhofer BM, Stringfield S, Foley EF, Harms BA, Heise CP and Kennedy GD: Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum. 56:1339–1348. 2013. View Article : Google Scholar : PubMed/NCBI
21	Chau I, Brown G, Cunningham D, Tait D, Wotherspoon A, Norman AR, Tebbutt N, Hill M, Ross PJ, Massey A and Oates J: Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 24:668–674. 2006. View Article : Google Scholar : PubMed/NCBI
22	Gao YH, Zhang X, An X, Cai MY, Zeng ZF, Chen G, Kong LH, Lin JZ, Wan DS, Pan ZZ and Ding PR: Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer. Strahlenther Onkol. 190:158–164. 2014. View Article : Google Scholar : PubMed/NCBI
23	Gao YH, Lin JZ, An X, Luo JL, Cai MY, Cai PQ, Kong LH, Liu GC, Tang JH, Chen G, et al: Neoadjuvant sandwich treatment with oxaliplatin and capecitabine administered prior to, concurrently with, and following radiation therapy in locally advanced rectal cancer: A prospective phase 2 trial. Int J Radiat Oncol Biol Phys. 90:1153–1160. 2014. View Article : Google Scholar : PubMed/NCBI
24	Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião GP and Gama-Rodrigues J: Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: Results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum. 52:1927–1934. 2009. View Article : Google Scholar : PubMed/NCBI
25	Larsen FO, Markussen A, Jensen BV, Fromm AL, Vistisen KK, Parner VK, Linnemann D, Hansen RH, Johannesen HH and Schou JV: Capecitabine and oxaliplatin before, during, and after radiotherapy for High-Risk rectal cancer. Clin Colorectal Cancer. 16:e7–e14. 2017. View Article : Google Scholar : PubMed/NCBI
26	Wan J, Liu K, Li K, Li G and Zhang Z: Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy? Radiat Oncol. 10:1622015. View Article : Google Scholar : PubMed/NCBI
27	Helbling D, Bodoky G, Gautschi O, Sun H, Bosman F, Gloor B, Burkhard R, Winterhalder R, Madlung A, Rauch D, et al: Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): A randomized, multicenter, phase II trial SAKK 41/07. Ann Oncol. 24:718–725. 2013. View Article : Google Scholar : PubMed/NCBI
28	Engineer R, Ostwal V, Arya S, Gupta P, Chopra S, Patil P, Jatal S and Saklani A: Additional chemotherapy and salvage surgery for poor response to chemoradiotherapy in rectal cancers. Asia Pac J Clin Oncol. 13:322–328. 2017. View Article : Google Scholar : PubMed/NCBI