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Erschienen in: Current Colorectal Cancer Reports 6/2016

29.09.2016 | Adjuvant Therapy for Colon Cancers (AB Benson III and A de Gramont, Section Editors)

Ongoing Adjuvant/Neoadjuvant Trials in Resectable Metastatic Colorectal Cancer

verfasst von: Daniel Krell, Rob Glynne-Jones

Erschienen in: Current Colorectal Cancer Reports | Ausgabe 6/2016

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Abstract

The treatment of patients with colorectal cancer with colorectal liver metastases remains an exciting challenge for the multidisciplinary team. The role and choice of induction chemotherapy, the timing of surgery in resectable disease and the prioritisation of resection of the primary or the metastases are all still controversial. A true multidisciplinary approach and individualisation of treatment strategies are recommended.
Literatur
1.
Zurück zum Zitat Leporrier J, Maurel J, Chiche L, et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93:465–74.CrossRefPubMed Leporrier J, Maurel J, Chiche L, et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93:465–74.CrossRefPubMed
2.
Zurück zum Zitat Huiskens J, van Gulik TM, van Lienden KP, et al. Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2015;15:365.CrossRefPubMedPubMedCentral Huiskens J, van Gulik TM, van Lienden KP, et al. Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2015;15:365.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818–25.CrossRefPubMedPubMedCentral Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818–25.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Shah SA, Bromberg R, Coates A, Rempel E, Simunovic M, Gallinger S. Survival after liver resection for metastatic colorectal carcinoma in a large population. J Am Coll Surg. 2007;205:676–83.CrossRefPubMed Shah SA, Bromberg R, Coates A, Rempel E, Simunovic M, Gallinger S. Survival after liver resection for metastatic colorectal carcinoma in a large population. J Am Coll Surg. 2007;205:676–83.CrossRefPubMed
5.
Zurück zum Zitat Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996;77(7):1254–62.CrossRefPubMed Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996;77(7):1254–62.CrossRefPubMed
6.
Zurück zum Zitat Sharma S, Camci C, Jabbour N. Management of hepatic metastasis from colorectal cancers: an update. J Hepatobiliary Pancreat Surg. 2008;15:570–80.CrossRefPubMed Sharma S, Camci C, Jabbour N. Management of hepatic metastasis from colorectal cancers: an update. J Hepatobiliary Pancreat Surg. 2008;15:570–80.CrossRefPubMed
7.
Zurück zum Zitat Lygidakis N, Ziras N, Parissis J. Resection versus resection combined with adjuvant pre- and post-operative chemotherapy—immunotherapy for metastatic colorectal liver cancer. A new look at an old problem. Hepatogastroenterology. 1995;42:155–61.PubMed Lygidakis N, Ziras N, Parissis J. Resection versus resection combined with adjuvant pre- and post-operative chemotherapy—immunotherapy for metastatic colorectal liver cancer. A new look at an old problem. Hepatogastroenterology. 1995;42:155–61.PubMed
8.
Zurück zum Zitat Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy—an intergroup study. J Clin Oncol. 2002;20:1499–505.CrossRefPubMed Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy—an intergroup study. J Clin Oncol. 2002;20:1499–505.CrossRefPubMed
9.
Zurück zum Zitat Parks R, Gonen M, Kemeny N, Jarnagin W, D’Angelica M, DeMatteo R, et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. J Am Coll Surg. 2007;204:753–61.CrossRefPubMed Parks R, Gonen M, Kemeny N, Jarnagin W, D’Angelica M, DeMatteo R, et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. J Am Coll Surg. 2007;204:753–61.CrossRefPubMed
10.•
Zurück zum Zitat Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 resection for advanced colorectal liver metastases in the era of modern effective chemotherapy. World J Surg. 2016;40(5):1191–9. This retrospective study of 466 patients treated between 1999 and 2010 in a major centre of expertise suggests that with modern combination chemotherapy, R1 resection is less crucial in responders to neoadjuvant chemotherapy. Additional postoperative chemotherapy may also protect from recurrences whatever the margin resection status.CrossRefPubMed Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 resection for advanced colorectal liver metastases in the era of modern effective chemotherapy. World J Surg. 2016;40(5):1191–9. This retrospective study of 466 patients treated between 1999 and 2010 in a major centre of expertise suggests that with modern combination chemotherapy, R1 resection is less crucial in responders to neoadjuvant chemotherapy. Additional postoperative chemotherapy may also protect from recurrences whatever the margin resection status.CrossRefPubMed
11.
Zurück zum Zitat Sanoff HK, Sargent DJ, Campbell ME, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26:5721–7.CrossRefPubMedPubMedCentral Sanoff HK, Sargent DJ, Campbell ME, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26:5721–7.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307(13):1383–93.CrossRefPubMedPubMedCentral Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307(13):1383–93.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Adam R, De Gramont A, Figueras J, et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist. 2012;17:1225–39.CrossRefPubMedPubMedCentral Adam R, De Gramont A, Figueras J, et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist. 2012;17:1225–39.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422.CrossRefPubMed Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422.CrossRefPubMed
15.
Zurück zum Zitat Bismuth H, Adam R, Lévi F, Farabos C, Waechter F, Castaing D, et al. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224:509–20.CrossRefPubMedPubMedCentral Bismuth H, Adam R, Lévi F, Farabos C, Waechter F, Castaing D, et al. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224:509–20.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Nordlinger B, Sorbye H, Glimelius B, EORTC Gastro-Intestinal Tract Cancer Group, Cancer Research UK, Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO), et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16.CrossRefPubMedPubMedCentral Nordlinger B, Sorbye H, Glimelius B, EORTC Gastro-Intestinal Tract Cancer Group, Cancer Research UK, Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO), et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16.CrossRefPubMedPubMedCentral
17.••
Zurück zum Zitat Primrose J, Falk S, Finch-Jones M, Valle J, Sherlock D, Hornbuckle J, et al. A randomized clinical trial of chemotherapy compared to chemotherapy in combination with cetuximab in k-RAS wild-type patients with operable metastases from colorectal cancer: the new EPOC study. Lancet Oncol. 2014;15(6):601–11. This randomised phase III trial has caused huge controversy (see J Clin Oncol correspondence Nordlinger et al 2015).The study suggests that the addition of cetuximab to chemotherapy in resectable (but multiple) CRLM is associated with a worse outcome. Criticisms have focussed on the changing eligibility criteria, multiple options for chemotherapy and poor quality of the surgery.CrossRefPubMed Primrose J, Falk S, Finch-Jones M, Valle J, Sherlock D, Hornbuckle J, et al. A randomized clinical trial of chemotherapy compared to chemotherapy in combination with cetuximab in k-RAS wild-type patients with operable metastases from colorectal cancer: the new EPOC study. Lancet Oncol. 2014;15(6):601–11. This randomised phase III trial has caused huge controversy (see J Clin Oncol correspondence Nordlinger et al 2015).The study suggests that the addition of cetuximab to chemotherapy in resectable (but multiple) CRLM is associated with a worse outcome. Criticisms have focussed on the changing eligibility criteria, multiple options for chemotherapy and poor quality of the surgery.CrossRefPubMed
18.
Zurück zum Zitat National Clinical Practice Guidelines in Oncology (NCCN Guidelines): Rectal Cancer Version 2.2016 www.ncrn.org. (last accessed 15/06/2016) National Clinical Practice Guidelines in Oncology (NCCN Guidelines): Rectal Cancer Version 2.2016 www.​ncrn.​org. (last accessed 15/06/2016)
20.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefPubMed Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefPubMed
21.
Zurück zum Zitat Folprecht G, Grothey A, Alberts S, et al. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol. 2005;16:1311–9.CrossRefPubMed Folprecht G, Grothey A, Alberts S, et al. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol. 2005;16:1311–9.CrossRefPubMed
22.
Zurück zum Zitat Folprecht G, Gruenberger T, Bechstein W, et al. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol. 2014;25:1018–25.CrossRefPubMed Folprecht G, Gruenberger T, Bechstein W, et al. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol. 2014;25:1018–25.CrossRefPubMed
23.
Zurück zum Zitat Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.CrossRefPubMed Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.CrossRefPubMed
24.
Zurück zum Zitat Jang KU, Kim CW, Kim KH, Lim SB, Yu CS, Kim TW, et al. Prognostic factors in terms of the number of metastatic nodules in patients with colorectal cancer liver metastases. Ann Coloproctol. 2016;32:92–100.CrossRefPubMedPubMedCentral Jang KU, Kim CW, Kim KH, Lim SB, Yu CS, Kim TW, et al. Prognostic factors in terms of the number of metastatic nodules in patients with colorectal cancer liver metastases. Ann Coloproctol. 2016;32:92–100.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Margonis GA, Sasaki K, Kim Y, Samaha M, Buettner S, Amini N, et al. Tumor biology rather than surgical technique dictates prognosis in colorectal cancer liver metastases. J Gastrointest Surg. 2016;6 [Epub ahead of print]. Margonis GA, Sasaki K, Kim Y, Samaha M, Buettner S, Amini N, et al. Tumor biology rather than surgical technique dictates prognosis in colorectal cancer liver metastases. J Gastrointest Surg. 2016;6 [Epub ahead of print].
26.
Zurück zum Zitat de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938–47.PubMed de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938–47.PubMed
27.
Zurück zum Zitat Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000;343(13):905–14.CrossRefPubMed Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000;343(13):905–14.CrossRefPubMed
28.
Zurück zum Zitat Douillard J, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28:4697–705.CrossRefPubMed Douillard J, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28:4697–705.CrossRefPubMed
29.
Zurück zum Zitat Van Cutsem E, Kohne C, Lang I, Folprecht G, Nowacki M, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29:2011–9.CrossRefPubMed Van Cutsem E, Kohne C, Lang I, Folprecht G, Nowacki M, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29:2011–9.CrossRefPubMed
30.
Zurück zum Zitat Okines A, Puerto O, Cunningham D, Chau I, Van Cutsem E, Saltz L, et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer. 2009;101:1033–8.CrossRefPubMedPubMedCentral Okines A, Puerto O, Cunningham D, Chau I, Van Cutsem E, Saltz L, et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer. 2009;101:1033–8.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Ribero D, Wang H, Donadon M, et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110(12):2761–7.CrossRefPubMed Ribero D, Wang H, Donadon M, et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110(12):2761–7.CrossRefPubMed
32.
Zurück zum Zitat Gruenberger B, Tamandl D, Schueller J, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26(11):1830–5.CrossRefPubMed Gruenberger B, Tamandl D, Schueller J, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26(11):1830–5.CrossRefPubMed
33.
Zurück zum Zitat Bertolini F, Malavasi N, Scarabelli L, et al. FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer. Br J Cancer. 2011;104(7):1079–84.CrossRefPubMedPubMedCentral Bertolini F, Malavasi N, Scarabelli L, et al. FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer. Br J Cancer. 2011;104(7):1079–84.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Wong R, Cunningham D, Barbachano Y, et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011;22(9):2042–8.CrossRefPubMed Wong R, Cunningham D, Barbachano Y, et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011;22(9):2042–8.CrossRefPubMed
35.
Zurück zum Zitat Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology. Br J Cancer. 2006;94:798–805.CrossRefPubMedPubMedCentral Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology. Br J Cancer. 2006;94:798–805.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6.CrossRefPubMed Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6.CrossRefPubMed
37.
Zurück zum Zitat Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst. 2011;103:21–30.CrossRefPubMed Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst. 2011;103:21–30.CrossRefPubMed
38.•
Zurück zum Zitat Ychou M, Rivoire M, Thezenas S, Quenet F, Delpero JR, Rebischung C, et al. A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. The METHEP trial. Ann Surg Oncol. 2013;20(13):4289–97. In this phase II study in patients with initially unresectable or not optimally resectable CRLM, FOLFOXIRI showed a conversion rate to resectability of 67 %, and was much more effective than the standard conventional chemotherapy (FOLFIRI/FOLFOX4).On this basis the randomised phase II METHEP-2 confirmed triplet chemotherapy, in association with a targeted therapy, showed a higher rate of R0/R1 resections than standard (FOLFIRI or FOLFOX4) combined with the same targeted therapy, but with a statistically significant difference in terms of OS.CrossRefPubMed Ychou M, Rivoire M, Thezenas S, Quenet F, Delpero JR, Rebischung C, et al. A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. The METHEP trial. Ann Surg Oncol. 2013;20(13):4289–97. In this phase II study in patients with initially unresectable or not optimally resectable CRLM, FOLFOXIRI showed a conversion rate to resectability of 67 %, and was much more effective than the standard conventional chemotherapy (FOLFIRI/FOLFOX4).On this basis the randomised phase II METHEP-2 confirmed triplet chemotherapy, in association with a targeted therapy, showed a higher rate of R0/R1 resections than standard (FOLFIRI or FOLFOX4) combined with the same targeted therapy, but with a statistically significant difference in terms of OS.CrossRefPubMed
40.
Zurück zum Zitat Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306–15.CrossRefPubMed Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306–15.CrossRefPubMed
41.
Zurück zum Zitat Hecht J, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009;27:672–80.CrossRefPubMed Hecht J, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009;27:672–80.CrossRefPubMed
42.
Zurück zum Zitat Tol J, Koopman M, Cats A, Rodenburg C, Creemers G, Schrama J, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360:563–72.CrossRefPubMed Tol J, Koopman M, Cats A, Rodenburg C, Creemers G, Schrama J, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360:563–72.CrossRefPubMed
43.
Zurück zum Zitat Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll H, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer. 2015;14(1):1–10.CrossRefPubMed Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll H, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer. 2015;14(1):1–10.CrossRefPubMed
44.
Zurück zum Zitat Fakih M. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33:1809–24.CrossRefPubMed Fakih M. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33:1809–24.CrossRefPubMed
45.
Zurück zum Zitat Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W, et al. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst. 2015;107(3). doi:10.1093/jnci/dju427. Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W, et al. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst. 2015;107(3). doi:10.​1093/​jnci/​dju427.
46.
Zurück zum Zitat Wang F, Bai L, Liu TS, Yu YY, He MM, Liu KY, et al. Right-sided colon cancer and left-sided colorectal cancers respond differently to cetuximab. Chin J Cancer. 2015;34(9):384–93.PubMed Wang F, Bai L, Liu TS, Yu YY, He MM, Liu KY, et al. Right-sided colon cancer and left-sided colorectal cancers respond differently to cetuximab. Chin J Cancer. 2015;34(9):384–93.PubMed
47.
Zurück zum Zitat Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol. 2014;32:5s (suppl; abstract LBA3). Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol. 2014;32:5s (suppl; abstract LBA3).
48.
Zurück zum Zitat Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75.CrossRefPubMed Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75.CrossRefPubMed
49.
Zurück zum Zitat Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7.CrossRefPubMed Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7.CrossRefPubMed
50.
Zurück zum Zitat Venook AP, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O’Neil BH, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2016;34:suppl; abstract 3504. Venook AP, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O’Neil BH, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2016;34:suppl; abstract 3504.
51.
Zurück zum Zitat Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94:982–99.CrossRefPubMedPubMedCentral Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94:982–99.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMed de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMed
53.
Zurück zum Zitat Spelt L, Andersson B, Nilsson J, Andersson R. Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. Eur J Surg Oncol. 2012;38:16–24.CrossRefPubMed Spelt L, Andersson B, Nilsson J, Andersson R. Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. Eur J Surg Oncol. 2012;38:16–24.CrossRefPubMed
54.
Zurück zum Zitat Nigri G, Petrucciani N, Ferla F, et al. Neoadjuvant chemotherapy for resectable colorectal liver metastases: what is the evidence? Results of a systematic review of comparative studies. Surg – J R Coll Surg Edinb Irel. 2015;13:83–90. Nigri G, Petrucciani N, Ferla F, et al. Neoadjuvant chemotherapy for resectable colorectal liver metastases: what is the evidence? Results of a systematic review of comparative studies. Surg – J R Coll Surg Edinb Irel. 2015;13:83–90.
55.
Zurück zum Zitat Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240(6):1052–61.CrossRefPubMedPubMedCentral Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240(6):1052–61.CrossRefPubMedPubMedCentral
56.
Zurück zum Zitat Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243(1):1–7.CrossRefPubMedPubMedCentral Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243(1):1–7.CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Reddy SK, Barbas AS, Turley RS, et al. A standard definition of major hepatectomy: resection of four or more liver segments. HPB (Oxford). 2011;13:494–502.CrossRef Reddy SK, Barbas AS, Turley RS, et al. A standard definition of major hepatectomy: resection of four or more liver segments. HPB (Oxford). 2011;13:494–502.CrossRef
58.
Zurück zum Zitat Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–72.CrossRefPubMed Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–72.CrossRefPubMed
59.
Zurück zum Zitat Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94:274–86.CrossRefPubMed Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94:274–86.CrossRefPubMed
60.
Zurück zum Zitat Grat M, Hoówko W, Lewandowski Z, et al. Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases. HPB (Oxford). 2013;15:352–8.CrossRef Grat M, Hoówko W, Lewandowski Z, et al. Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases. HPB (Oxford). 2013;15:352–8.CrossRef
61.
Zurück zum Zitat Choti MA, Thomas M, Wong SL, et al. Surgical resection preferences and perceptions among medical oncologists treating liver metastases from colorectal cancer. Ann Surg Oncol. 2016;23(2):375–81.CrossRefPubMed Choti MA, Thomas M, Wong SL, et al. Surgical resection preferences and perceptions among medical oncologists treating liver metastases from colorectal cancer. Ann Surg Oncol. 2016;23(2):375–81.CrossRefPubMed
62.
Zurück zum Zitat Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198–204.CrossRefPubMed Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198–204.CrossRefPubMed
63.
Zurück zum Zitat André T, Boni C, Navarro M, et al. 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;27:3109–16.CrossRefPubMed André T, Boni C, Navarro M, et al. 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;27:3109–16.CrossRefPubMed
64.
Zurück zum Zitat Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465–71.CrossRefPubMed Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465–71.CrossRefPubMed
65.
Zurück zum Zitat Adams RA, Meade AM, Seymour MT, MRC COIN Trial Investigators, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642–53.CrossRefPubMedPubMedCentral Adams RA, Meade AM, Seymour MT, MRC COIN Trial Investigators, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642–53.CrossRefPubMedPubMedCentral
66.
Zurück zum Zitat Hegewisch-Becker S, Graeven U, Lerchenmüller CA, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015;16:1355–69.CrossRefPubMed Hegewisch-Becker S, Graeven U, Lerchenmüller CA, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015;16:1355–69.CrossRefPubMed
67.
Zurück zum Zitat Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015;385:1843–52.CrossRefPubMed Simkens LHJ, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015;385:1843–52.CrossRefPubMed
68.
Zurück zum Zitat Finlay IG, Meek D, Brunton F, McCardle CS. Growth rate of hepatic metastases in colorectal cancer. Br J Surg. 1989;76:652.CrossRefPubMed Finlay IG, Meek D, Brunton F, McCardle CS. Growth rate of hepatic metastases in colorectal cancer. Br J Surg. 1989;76:652.CrossRefPubMed
69.
Zurück zum Zitat Kito A, Tanaka K, Fujimaki H, Nakazawa M, Togo S, Minami M. Tumor doubling time and local immune response to hepatic metastases from colorectal cancer. J Surg Oncol. 2007;96:525–33.CrossRefPubMed Kito A, Tanaka K, Fujimaki H, Nakazawa M, Togo S, Minami M. Tumor doubling time and local immune response to hepatic metastases from colorectal cancer. J Surg Oncol. 2007;96:525–33.CrossRefPubMed
70.
Zurück zum Zitat Lim E, Wiggans MG, Shahtahmassebi G, et al. Rebound growth of hepatic colorectal metastases after neo-adjuvant chemotherapy: effect on survival after resection. HPB (Oxford). 2016;18(7):586–92.CrossRef Lim E, Wiggans MG, Shahtahmassebi G, et al. Rebound growth of hepatic colorectal metastases after neo-adjuvant chemotherapy: effect on survival after resection. HPB (Oxford). 2016;18(7):586–92.CrossRef
71.
Zurück zum Zitat Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18. discussion 318-21.CrossRefPubMedPubMedCentral Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18. discussion 318-21.CrossRefPubMedPubMedCentral
72.
Zurück zum Zitat Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252(5):774–87.CrossRefPubMed Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252(5):774–87.CrossRefPubMed
73.
Zurück zum Zitat Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.CrossRefPubMed Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.CrossRefPubMed
74.
Zurück zum Zitat Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255(2):237–47.CrossRefPubMed Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA. Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg. 2012;255(2):237–47.CrossRefPubMed
75.
Zurück zum Zitat Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.CrossRefPubMed Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.CrossRefPubMed
76.
Zurück zum Zitat Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.CrossRefPubMed Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.CrossRefPubMed
77.
Zurück zum Zitat Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009;20(12):1964–70.CrossRefPubMed Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009;20(12):1964–70.CrossRefPubMed
Metadaten
Titel
Ongoing Adjuvant/Neoadjuvant Trials in Resectable Metastatic Colorectal Cancer
verfasst von
Daniel Krell
Rob Glynne-Jones
Publikationsdatum
29.09.2016
Verlag
Springer US
Erschienen in
Current Colorectal Cancer Reports / Ausgabe 6/2016
Print ISSN: 1556-3790
Elektronische ISSN: 1556-3804
DOI
https://doi.org/10.1007/s11888-016-0342-5

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