Rectal cancer - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main rectal cancer page for regimens that include active anticancer treatment.
=Neoadjuvant therapy=
==No neoadjuvant therapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Oates et al. 1996 	1981-1989 	Phase 3 (C)	RT 	Seems to have shorter DFS
Cedermark et al. 1997 (Swedish Rectal Cancer Trial)	1987-1990 	Phase 3 (C)	RT 	Shorter OS
Kapiteijn et al. 2001 	1996-1999 	Phase 3 (C)	RT 	Lower local recurrence rate
No neoadjuvant therapy.
===References===
# Oates GD, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet. 1996 Dec 14;348(9042):1605-10. link to original article EuroPMC
# Swedish Rectal Cancer Trial: Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N; Swedish Rectal Cancer Trial investigators. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. link to original article EuroPMC
## Update: Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. link to original article EuroPMC
# Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. link to original article EuroPMC
# UNICANCER-PRODIGE 23: Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. Epub 2021 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01804790
##Update: Conroy T, Castan F, Etienne PL, Rio E, Mesgouez-Nebout N, Evesque L, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Boilève A, Delaye M, Gourgou S, Pezzella V, Borg C. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial. Ann Oncol. 2024 Oct;35(10):873-881. Epub 2024 Jul 8. link to original article EuroPMC
=Adjuvant therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mittelman et al. 1985 	1975-1980 	Phase 3 (C)	1. 5-FU & Semustine 	Not reported
Mittelman et al. 1985 	1975-1980 	Phase 3 (C)	2. 5-FU, Semustine, RT	Shorter RFS
Mittelman et al. 1985 	1975-1980 	Phase 3 (C)	3. RT 	Not reported
Fisher et al. 1988 (NSABP R-01) 	1977-1986 	Phase 3 (C)	1. MOF 	Not reported
Fisher et al. 1988 (NSABP R-01) 	1977-1986 	Phase 3 (C)	2. RT 	Did not meet efficacy endpoints of DFS/OS
Amott et al. 1996 	1984-1989 	Phase 3 (C)	RT 	Lower local recurrence rate
Sainato et al. 2014 (I-CNR-RT) 	1992-2001 	Phase 3 (C)	FULV 	Did not meet primary endpoint of OS
Hamaguchi et al. 2010 (NSAS-CC) 	1996-2001 	Phase 3 (C)	UFT 	Seems to have shorter OS
Breugom et al. 2014 (PROCTOR) 	2000-2013 	Phase 3 (C)	FULV 	Did not meet primary endpoint of OS
Breugom et al. 2014 (SCRIPT) 	2000-2013 	Phase 3 (C)	Capecitabine 	Did not meet primary endpoint of OS
Glynne-Jones et al. 2014 (Chronicle)	2004-2008 	Phase 3 (C)	XELOX 	Did not meet primary endpoint of DFS
Okuno et al. 2017 (JFMC38) 	2011-2013 	Phase 3 (C)	UFT & PSK 	Did not meet primary endpoint of DFS
No further treatment after (neoadjuvant therapy) and surgery.
====Preceding treatment====
*Mittelman et al. 1985 & JFMC38: Surgery
*Chronicle: Neoadjuvant 5-FU-based chemoradiotherapy, then surgery
*I-CNR-RT: Neoadjuvant FULV & RT, then surgery
*PROCTOR & SCRIPT: Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
===References===
# Mittelman A, Holyoke ED, Stablein DM, Novak JW, Thomas PRM, Moertel CG, Weiland LH, Livstone EM, Bruckner HW, Knowlton AH; Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. 1985 Jun 6;312(23):1465-72. link to original article EuroPMC
# NSABP R-01: Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. link to original article EuroPMC
# Amott SJ, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet. 1996 Dec 14;348(9042):1610-4. link to original article EuroPMC
# NSAS-CC: Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011 Mar;67(3):587-96. Epub 2010 May 19. link to original article EuroPMC NCT00152230
# Chronicle: Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, Ledermann J, Sebag-Montefiore D. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014 Jul;25(7):1356-62. Epub 2014 Apr 8. link to original article EuroPMC NCT00427713
# I-CNR-RT: Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, Aristei C, Vidali C, Conti M, Galardi A, Ponticelli P, Friso ML, Iannone T, Osti FM, Manfredi B, Coppola M, Orlandini C, Cionini L. No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014 Nov;113(2):223-9. Epub 2014 Nov 14. link to original article EuroPMC
# PROCTOR/SCRIPT: Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. link to original article EuroPMC ISRCTN36266738
# JFMC38: Okuno K, Aoyama T, Oba K, Yokoyama N, Matsuhashi N, Kunieda K, Nishimura Y, Akamatsu H, Kobatake T, Morita S, Yoshikawa T, Sakamoto J, Saji S. Randomized phase III trial comparing surgery alone to UFT + PSK for stage II rectal cancer (JFMC38 trial). Cancer Chemother Pharmacol. 2018 Jan;81(1):65-71. Epub 2017 Nov 1. link to original article link to PMC article EuroPMC
Category:Rectal cancer regimens
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Category:Colorectal cancers
Category:Null regimens