Skip to main content
Top
Published in: Current Colorectal Cancer Reports 1/2021

01-02-2021 | Rectal Cancer | Systemic Therapies in Colorectal Cancer (SM Kazmi, Section Editor)

Review and Updates on Approaches to Neoadjuvant Chemotherapy in Rectal Cancer

Authors: Thomas Holden, Namrata Vijayvergia

Published in: Current Colorectal Cancer Reports | Issue 1/2021

Login to get access

Abstract

Purpose of Review

The currently established standard of care treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant fluorouracil and oxaliplatin. The body of evidence that supports this treatment has grown over the last 20 years. However, recent advances and ongoing studies seek to further evaluate the role of neoadjuvant chemotherapy with and without radiation and total neoadjuvant therapy (TNT). In this article, we review the current literature as well as investigate the emerging role of TNT for patients with LARC and comment on updates utilizing combination neoadjuvant chemotherapy in early-stage rectal cancer.

Recent Findings

Evidence for the current standard of neoadjuvant CRT comes from well-established randomized phase III trials as well as emerging evidence on merits of TNT. There is a growing body of literature including retrospective analysis and ongoing clinical trials that look at upfront induction chemotherapy in addition to CRT prior to surgical resection leading to more effective delivery of systemic therapy and increases in response to treatment. Neoadjuvant combination chemotherapy is also being investigated in early-stage low rectal tumors to see if rates of local excision will increase compared to radical excision.

Summary

Current evidence continues to support neoadjuvant CRT as the standard treatment for LARC. There is an increasing body of evidence to support TNT in LARC as an effective treatment strategy that better ensures delivery of systemic therapy leading to higher rates of complete response (CR) and is encouraging for the development of non-operative protocols. There is ongoing evaluation looking at the benefit of novel sensitizers added to neoadjuvant therapy and ongoing investigation into upfront combination chemotherapy with selective use of radiation in upper rectal cancers.
Literature
2.
go back to reference Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19:2822–32.PubMedCrossRef Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19:2822–32.PubMedCrossRef
3.
go back to reference Benson AB, Al-Hawary MM, Arain MA, et al. 2020. NCCN Guidelines Version 2.2020 Rectal Cancer Continue NCCN Guidelines Panel Disclosures. Accessed 3 Mar 2020. Benson AB, Al-Hawary MM, Arain MA, et al. 2020. NCCN Guidelines Version 2.2020 Rectal Cancer Continue NCCN Guidelines Panel Disclosures. Accessed 3 Mar 2020.
4.•
go back to reference Cercek A, Roxburgh CSD, Strombom P, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4:e180071 A retrospective cohort analysis revealing higher rates of completion of planned treatment in patients undergoing TNT versus traditional adjuvant chemotherapy.PubMedCrossRefPubMedCentral Cercek A, Roxburgh CSD, Strombom P, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4:e180071 A retrospective cohort analysis revealing higher rates of completion of planned treatment in patients undergoing TNT versus traditional adjuvant chemotherapy.PubMedCrossRefPubMedCentral
5.
go back to reference Peeters KCMJ, Marijnen CAM, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, 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. Ann Surg. 2007;246:693–701.PubMedCrossRef Peeters KCMJ, Marijnen CAM, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, 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. Ann Surg. 2007;246:693–701.PubMedCrossRef
6.
go back to reference Tekkis PP, Heriot AG, Smith J, Thompson MR, Finan P, Stamatakis JD. Comparison of circumferential margin involvement between restrorative and nonrestorative resections for rectal cancer. Color Dis. 2005;7:369–74.CrossRef Tekkis PP, Heriot AG, Smith J, Thompson MR, Finan P, Stamatakis JD. Comparison of circumferential margin involvement between restrorative and nonrestorative resections for rectal cancer. Color Dis. 2005;7:369–74.CrossRef
7.
go back to reference Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.PubMedCrossRefPubMedCentral Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.PubMedCrossRefPubMedCentral
8.•
go back to reference Leichman CG, McDonough SL, Smalley SR, et al. Cetuximab combined with induction oxaliplatin and capecitabine, followed by neoadjuvant chemoradiation for locally advanced rectal cancer: SWOG 0713. Clin Colorectal Cancer. 2018;17:e121–5 Phase II study showing the addition of EGFR-targeted antibody cetuximab to neoadjuvant CRT in KRAS wild-type patients does not improve pCR.PubMedCrossRef Leichman CG, McDonough SL, Smalley SR, et al. Cetuximab combined with induction oxaliplatin and capecitabine, followed by neoadjuvant chemoradiation for locally advanced rectal cancer: SWOG 0713. Clin Colorectal Cancer. 2018;17:e121–5 Phase II study showing the addition of EGFR-targeted antibody cetuximab to neoadjuvant CRT in KRAS wild-type patients does not improve pCR.PubMedCrossRef
9.
go back to reference Dewdney A, Cunningham D, Tabernero J, et al. Multicenter randomized phase ii clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). 2012. https://doi.org/10.1200/JCO.2011.39.6036. Dewdney A, Cunningham D, Tabernero J, et al. Multicenter randomized phase ii clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). 2012. https://​doi.​org/​10.​1200/​JCO.​2011.​39.​6036.
10.
go back to reference Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.PubMedCrossRef Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.PubMedCrossRef
11.
go back to reference Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1926–33.PubMedCrossRef Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1926–33.PubMedCrossRef
12.
go back to reference Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–88.PubMedCrossRef Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–88.PubMedCrossRef
13.
go back to reference Schrag D, Weiser MR, Goodman KA, Gon̈en M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32:513–8.PubMedCrossRefPubMedCentral Schrag D, Weiser MR, Goodman KA, Gon̈en M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32:513–8.PubMedCrossRefPubMedCentral
14.
go back to reference Sainato A, Cernusco Luna Nunzia V, Valentini V, de Paoli A, Maurizi ER, Lupattelli M, et al. 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;113:223–9.PubMedCrossRef Sainato A, Cernusco Luna Nunzia V, Valentini V, de Paoli A, Maurizi ER, Lupattelli M, et al. 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;113:223–9.PubMedCrossRef
15.
go back to reference Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CBM, Fokstuen T, et al. 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;26:696–701.PubMedCrossRef Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CBM, Fokstuen T, et al. 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;26:696–701.PubMedCrossRef
16.
go back to reference Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, et al. 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;25:1356–62.PubMedCrossRef Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, et al. 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;25:1356–62.PubMedCrossRef
17.
go back to reference Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.PubMedCrossRef Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.PubMedCrossRef
18.
go back to reference Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99:918–28.PubMedCrossRef Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99:918–28.PubMedCrossRef
19.
go back to reference George TJ, Allegra CJ, Yothers G. Neoadjuvant rectal (NAR) score: a new surrogate endpoint in rectal cancer clinical trials. Curr Colorectal Cancer Rep. 2015;11:275–80.PubMedCrossRefPubMedCentral George TJ, Allegra CJ, Yothers G. Neoadjuvant rectal (NAR) score: a new surrogate endpoint in rectal cancer clinical trials. Curr Colorectal Cancer Rep. 2015;11:275–80.PubMedCrossRefPubMedCentral
20.
go back to reference Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, 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 Clin Oncol. 2011;29:2773–80.PubMedCrossRef Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, 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 Clin Oncol. 2011;29:2773–80.PubMedCrossRef
21.
go back to reference Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30:4558–65.PubMedCrossRef Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30:4558–65.PubMedCrossRef
22.
go back to reference Schmoll H-J, Haustermans K, Price TJ, Nordlinger B, Hofheinz R, Daisne JF, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. J Clin Oncol. 2014;32:3501–3501.CrossRef Schmoll H-J, Haustermans K, Price TJ, Nordlinger B, Hofheinz R, Daisne JF, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. J Clin Oncol. 2014;32:3501–3501.CrossRef
24.
go back to reference Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, et al. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016;34:3300–7.PubMedCrossRef Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, et al. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016;34:3300–7.PubMedCrossRef
25.
go back to reference O’Connell MJ, Colangelo LH, Beart RW, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from national surgical adjuvant breast and bowel project trial R-04. J Clin Oncol. 2014;32:1927–34.PubMedCrossRefPubMedCentral O’Connell MJ, Colangelo LH, Beart RW, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from national surgical adjuvant breast and bowel project trial R-04. J Clin Oncol. 2014;32:1927–34.PubMedCrossRefPubMedCentral
26.
go back to reference Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:979–89.PubMedCrossRef Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:979–89.PubMedCrossRef
27.
go back to reference Gollins S, Sun Myint A, Haylock B, Wise M, Saunders M, Neupane R, et al. Preoperative chemoradiotherapy using concurrent capecitabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes. J Clin Oncol. 2011;29:1042–9.PubMedCrossRef Gollins S, Sun Myint A, Haylock B, Wise M, Saunders M, Neupane R, et al. Preoperative chemoradiotherapy using concurrent capecitabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes. J Clin Oncol. 2011;29:1042–9.PubMedCrossRef
28.
go back to reference Navarro M, Dotor E, Rivera F, Sánchez-Rovira P, Vega-Villegas ME, Cervantes A, et al. A phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66:201–5.PubMedCrossRef Navarro M, Dotor E, Rivera F, Sánchez-Rovira P, Vega-Villegas ME, Cervantes A, et al. A phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66:201–5.PubMedCrossRef
29.
go back to reference Mohiuddin M, Paulus R, Mitchell E, Hanna N, Yuen A, Nichols R, et al. Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer. Int J Radiat Oncol Biol Phys. 2013;86:523–8.PubMedCrossRefPubMedCentral Mohiuddin M, Paulus R, Mitchell E, Hanna N, Yuen A, Nichols R, et al. Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer. Int J Radiat Oncol Biol Phys. 2013;86:523–8.PubMedCrossRefPubMedCentral
31.
go back to reference Mengual-Ballester M, García-Marín JA, Pellicer-Franco E, Guillén-Paredes MP, García-García ML, Cases-Baldó MJ, et al. Ileostomías de protección: complicaciones y mortalidad asociadas a su cierre. Rev Esp Enferm Dig. 2012;104:350–4.PubMedCrossRef Mengual-Ballester M, García-Marín JA, Pellicer-Franco E, Guillén-Paredes MP, García-García ML, Cases-Baldó MJ, et al. Ileostomías de protección: complicaciones y mortalidad asociadas a su cierre. Rev Esp Enferm Dig. 2012;104:350–4.PubMedCrossRef
32.
go back to reference Chau I, Brown G, Cunningham D, Tait D, Wotherspoon A, Norman AR, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.PubMedCrossRef Chau I, Brown G, Cunningham D, Tait D, Wotherspoon A, Norman AR, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.PubMedCrossRef
33.
go back to reference 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 Cáncer de Recto 3 study. J Clin Oncol. 2010;28:859–65.PubMedCrossRef 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 Cáncer de Recto 3 study. J Clin Oncol. 2010;28:859–65.PubMedCrossRef
34.
go back to reference Sclafani F, Peckitt C, Cunningham D, Evans J, Brown G, Tabernero J, et al. Panex: a pooled analysis of EXPERT and EXPERT-C, two trials of neoadjuvant chemotherapy (NACT) and chemoradiotherapy (CRT) in high-risk locally advanced rectal cancer (LARC). J Clin Oncol. 2014;32:3575–3575. Sclafani F, Peckitt C, Cunningham D, Evans J, Brown G, Tabernero J, et al. Panex: a pooled analysis of EXPERT and EXPERT-C, two trials of neoadjuvant chemotherapy (NACT) and chemoradiotherapy (CRT) in high-risk locally advanced rectal cancer (LARC). J Clin Oncol. 2014;32:3575–3575.
35.•
go back to reference Conroy T, Lamfichekh N, Etienne P-L, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: final results of PRODIGE 23 phase III trial, a UNICANCER GI trial. J Clin Oncol. 2020;38:4007–4007 Investigated and found compliance to CRT was not negatively impacted by neoadjuvant chemotherapy and that TNT significantly increased ypCR rate as well as 3-year DFS compared to traditional CRT and adjuvant chemotherapy.CrossRef Conroy T, Lamfichekh N, Etienne P-L, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: final results of PRODIGE 23 phase III trial, a UNICANCER GI trial. J Clin Oncol. 2020;38:4007–4007 Investigated and found compliance to CRT was not negatively impacted by neoadjuvant chemotherapy and that TNT significantly increased ypCR rate as well as 3-year DFS compared to traditional CRT and adjuvant chemotherapy.CrossRef
36.
go back to reference van Dijk TH, Tamas K, Beukema JC, Beets GL, Gelderblom AJ, de Jong KP, et al. Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol. 2013;24:1762–9.PubMedCrossRef van Dijk TH, Tamas K, Beukema JC, Beets GL, Gelderblom AJ, de Jong KP, et al. Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol. 2013;24:1762–9.PubMedCrossRef
37.•
go back to reference Hospers G, Bahadoer RR, Dijkstra EA, et al. Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: the randomized RAPIDO trial. J Clin Oncol. 2020;38:4006–4006 An investigation of short-course radiotherapy followed by chemotherapy prior to TME compared to standard CRT. Results with significantly lower disease-related treatment failure rate in high-risk LARC patients.CrossRef Hospers G, Bahadoer RR, Dijkstra EA, et al. Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: the randomized RAPIDO trial. J Clin Oncol. 2020;38:4006–4006 An investigation of short-course radiotherapy followed by chemotherapy prior to TME compared to standard CRT. Results with significantly lower disease-related treatment failure rate in high-risk LARC patients.CrossRef
38.
go back to reference Feeney G, Sehgal R, Sheehan M, Hogan A, Regan M, Joyce M, et al. Neoadjuvant radiotherapy for rectal cancer management. World J Gastroenterol. 2019;25:4850–69.PubMedCrossRefPubMedCentral Feeney G, Sehgal R, Sheehan M, Hogan A, Regan M, Joyce M, et al. Neoadjuvant radiotherapy for rectal cancer management. World J Gastroenterol. 2019;25:4850–69.PubMedCrossRefPubMedCentral
39.•
go back to reference Deng Y, Chi P, Lan P, et al. Neoadjuvant modified folfox6 with or without radiation versus fluorouracil plus radiation for locally advanced rectal cancer: final results of the Chinese FOWARC trial. J Clin Oncol. 2019;37:3223–33 A phase III prospective study showing no difference in 3-year DFS and OS and less treatment-related toxicity with neoadjuvant chemotherapy alone compared to CRT.PubMedCrossRefPubMedCentral Deng Y, Chi P, Lan P, et al. Neoadjuvant modified folfox6 with or without radiation versus fluorouracil plus radiation for locally advanced rectal cancer: final results of the Chinese FOWARC trial. J Clin Oncol. 2019;37:3223–33 A phase III prospective study showing no difference in 3-year DFS and OS and less treatment-related toxicity with neoadjuvant chemotherapy alone compared to CRT.PubMedCrossRefPubMedCentral
40.
go back to reference Havenga K, Enker WE, Norstein J, Moriya Y, Heald RJ, van Houwelingen HC, et al. Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients. Eur J Surg Oncol. 1999;25:368–74.PubMedCrossRef Havenga K, Enker WE, Norstein J, Moriya Y, Heald RJ, van Houwelingen HC, et al. Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients. Eur J Surg Oncol. 1999;25:368–74.PubMedCrossRef
41.
go back to reference Bosset J-F, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.PubMedCrossRef Bosset J-F, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.PubMedCrossRef
42.
go back to reference Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.PubMedCrossRef Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.PubMedCrossRef
43.
go back to reference van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018;391:2537–45.PubMedCrossRef van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018;391:2537–45.PubMedCrossRef
44.•
go back to reference Garcia-Aguilar J, Patil S, Kim JK, Yuval JB, Thompson H, Verheij F, et al. Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial. J Clin Oncol. 2020;38:4008–4008 Prospective study that showed comparable DFS between induction and consolidation chemotherapy + CRT in addition to high organ preservation rate in the consolidation arm allowing adoption of a watch and wait approach in patients who achieve clinical complete response with TNT.CrossRef Garcia-Aguilar J, Patil S, Kim JK, Yuval JB, Thompson H, Verheij F, et al. Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial. J Clin Oncol. 2020;38:4008–4008 Prospective study that showed comparable DFS between induction and consolidation chemotherapy + CRT in addition to high organ preservation rate in the consolidation arm allowing adoption of a watch and wait approach in patients who achieve clinical complete response with TNT.CrossRef
45.
go back to reference Marijnen CAM, Kapiteijn E, van de Velde CJH, Martijn H, Steup WH, Wiggers T, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20:817–25.PubMedCrossRef Marijnen CAM, Kapiteijn E, van de Velde CJH, Martijn H, Steup WH, Wiggers T, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20:817–25.PubMedCrossRef
46.
go back to reference Hendren SK, O’Connor BI, Liu M, Asano T, Cohen Z, Swallow CJ, et al. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg. 2005;242:212–23.PubMedCrossRefPubMedCentral Hendren SK, O’Connor BI, Liu M, Asano T, Cohen Z, Swallow CJ, et al. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg. 2005;242:212–23.PubMedCrossRefPubMedCentral
47.
go back to reference Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, et al. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. JNCCN J Natl Compr Cancer Netw. 2014;12:513–9.CrossRef Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, et al. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. JNCCN J Natl Compr Cancer Netw. 2014;12:513–9.CrossRef
48.
go back to reference Verseveld M, de Graaf EJR, Verhoef C, van Meerten E, Punt CJA, de Hingh IHJT, et al. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg. 2015;102:853–60.PubMedCrossRef Verseveld M, de Graaf EJR, Verhoef C, van Meerten E, Punt CJA, de Hingh IHJT, et al. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg. 2015;102:853–60.PubMedCrossRef
49.
go back to reference Garcia-Aguilar J, Shi Q, Thomas CR, Chan E, Cataldo P, Marcet J, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19:384–91.PubMedCrossRef Garcia-Aguilar J, Shi Q, Thomas CR, Chan E, Cataldo P, Marcet J, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19:384–91.PubMedCrossRef
50.
go back to reference Pucciarelli S, de Paoli A, Guerrieri M, la Torre G, Maretto I, de Marchi F, et al. Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum. 2013;56:1349–56.PubMedCrossRef Pucciarelli S, de Paoli A, Guerrieri M, la Torre G, Maretto I, de Marchi F, et al. Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum. 2013;56:1349–56.PubMedCrossRef
Metadata
Title
Review and Updates on Approaches to Neoadjuvant Chemotherapy in Rectal Cancer
Authors
Thomas Holden
Namrata Vijayvergia
Publication date
01-02-2021
Publisher
Springer US
Published in
Current Colorectal Cancer Reports / Issue 1/2021
Print ISSN: 1556-3790
Electronic ISSN: 1556-3804
DOI
https://doi.org/10.1007/s11888-020-00462-3
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine