Low-dose Capecitabine Adjuvant Chemotherapy for Elderly Patients With Stage II/III Colorectal Cancer

Summary

Approximately half of colorectal cancer (CRC) patients were first diagnosed after 70 years old. However, compared with younger patients, elderly patients were often undertreated in chemotherapy due to their impaired tolerance. Recently, there have been great controversy on adjuvant chemotherapy strategy for stage II/III CRC patients. As an oral fluoropyrimidine, capecitabine has been demonstrated to be equivalent to i.v. 5-Fu/leucovorin regimen in stage III CRC patients. In light of fewer adverse effects and better flexibility, capecitabine was regarded as an ideal alternative for elderly CRC patients, but the optimal dosage for stage II/III elderly CRC patients still remains inconclusive. Our trial expected to prospectively randomized 710 postoperative stage II/III elderly CRC patients (between 70 and 90 years of age) to adjuvant mono-chemotherapy with a standard dose of capecitabine (2500 mg/m2/day) or a reduced dose (2000 mg/m2/day). This is a non-inferiority phase 3 trial with a primary endpoint of 3-year disease free survival (DFS), and other outcomes include 3-year overall survival(OS), completion rate, toxic and adverse effects and quality of life(Qol). By this trial, we aimed to achieve more precise evidence on the individualized adjuvant chemotherapy strategy for stage II/III elderly CRC patients.

Timeline

Start

2014-11

Primary completion

2017-12

Completion

2018-05

Publications

• Background Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
• Background Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, Brouwers M, Charette M, Haller DG. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004 Aug 15;22(16):3408-19. doi: 10.1200/JCO.2004.05.063. Epub 2004 Jun 15.
• Background Quasar Collaborative Group; Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9. doi: 10.1016/S0140-6736(07)61866-2.
• Background Folprecht G, Cunningham D, Ross P, Glimelius B, Di Costanzo F, Wils J, Scheithauer W, Rougier P, Aranda E, Hecker H, Kohne CH. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004 Sep;15(9):1330-8. doi: 10.1093/annonc/mdh344.
• Background McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E, O'Connell M, Twelves CJ, Saltz LB, Haller DG, Sargent DJ. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013 Jul 10;31(20):2600-6. doi: 10.1200/JCO.2013.49.6638. Epub 2013 Jun 3.
• Background Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001 Jun 6;93(11):850-7. doi: 10.1093/jnci/93.11.850.
• Background Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, Shepherd LE, Seitz JF, Francini G. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001 Oct 11;345(15):1091-7. doi: 10.1056/NEJMoa010957.
• Background Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. doi: 10.1200/JCO.2008.20.6771. Epub 2009 May 18.
• Background Papamichael D, Audisio R, Horiot JC, Glimelius B, Sastre J, Mitry E, Van Cutsem E, Gosney M, Kohne CH, Aapro M; SIOG. Treatment of the elderly colorectal cancer patient: SIOG expert recommendations. Ann Oncol. 2009 Jan;20(1):5-16. doi: 10.1093/annonc/mdn532. Epub 2008 Oct 15.
• Background Van Cutsem E, Hoff PM, Harper P, Bukowski RM, Cunningham D, Dufour P, Graeven U, Lokich J, Madajewicz S, Maroun JA, Marshall JL, Mitchell EP, Perez-Manga G, Rougier P, Schmiegel W, Schoelmerich J, Sobrero A, Schilsky RL. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer. 2004 Mar 22;90(6):1190-7. doi: 10.1038/sj.bjc.6601676.
• Background Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Muller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. doi: 10.1016/S1470-2045(12)70116-X. Epub 2012 Apr 13.
• Background Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. doi: 10.1056/NEJMoa043116.
• Background Chang HJ, Lee KW, Kim JH, Bang SM, Kim YJ, Kim DW, Kang SB, Lee JS. Adjuvant capecitabine chemotherapy using a tailored-dose strategy in elderly patients with colon cancer. Ann Oncol. 2012 Apr;23(4):911-8. doi: 10.1093/annonc/mdr329. Epub 2011 Aug 4.
• He Y, Liu P, Zhang Y, Deng X, Meng W, Wei M, Yang T, Wang Z, Qiu M. Low-dose capecitabine adjuvant chemotherapy in elderly stage II/III colorectal cancer patients (LC-ACEC): study protocol for a randomized controlled trial. Trials. 2015 May 29;16:238. doi: 10.1186/s13063-015-0753-7.

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