Skip to main content
Top
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: A systematic review and meta-analysis of randomized trials

Authors: Martina Wieser, Stefan Sauerland, Dirk Arnold, Wolff Schmiegel, Anke Reinacher-Schick

Published in: BMC Cancer | Issue 1/2010

Login to get access

Abstract

Background

The role of peri-operative chemotherapy in patients with resected stage IV colorectal cancer (CRC) remains to be defined. This study was aimed at evaluating the effectiveness of peri-operative chemotherapy in patients with resected stage IV CRC by performing a meta-analysis of relevant trials.

Methods

We performed a literature search to identify trials comparing patients with stage IV CRC receiving peri-operative chemotherapy and surgery with patients undergoing surgery alone. The hazard ratio (HR) was estimated to assess any survival advantage of peri-operative chemotherapy.

Results

Eight trials conducted on a total of 1174 patients were identified by a literature search. In these trials, HR estimates suggested that peri-operative chemotherapy yielded no survival advantage over surgery alone (HR, 0.94; 95%CI, 0.8-1.10; p = 0.43). In a subset analysis on intra-arterial chemotherapy alone, no survival benefit was evident (HR, 1.0; 95% CI, 0.84-1.21; p = 0.96; I2 = 30%), whereas in the trials involving systemic chemotherapy, the difference between the groups approached statistical significance (HR, 0.74; 95% CI, 0.53-1.04; p = 0.08; I2 = 0%). Both peri-operative treatment groups had a significant recurrence-free survival benefit (HR, 0.78; 95% CI, 0.65-0.95; P = 0.01 for hepatic arterial infusion; and HR, 0.75; 95% CI, 0.62-0.91; p = 0.003 for systemic therapy). The toxicities of chemotherapy were acceptable in most trials.

Conclusions

This is the first meta-analysis demonstrating the importance of peri-operative chemotherapy in the treatment of resected stage IV CRC. Although the results must be carefully interpreted because of some limitations, critical issues were identified that must be resolved by future studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Boyle P, Ferlay J: Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005, 16 (3): 481-488. 10.1093/annonc/mdi098.CrossRefPubMed Boyle P, Ferlay J: Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005, 16 (3): 481-488. 10.1093/annonc/mdi098.CrossRefPubMed
2.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA: a cancer journal for clinicians. 2009, 59 (4): 225-249. 10.3322/caac.20006. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA: a cancer journal for clinicians. 2009, 59 (4): 225-249. 10.3322/caac.20006.
3.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.
4.
go back to reference Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertino JR, Turnbull AD, Sullivan D, Stockman J, et al: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. The New England journal of medicine. 1999, 341 (27): 2039-2048. 10.1056/NEJM199912303412702.CrossRefPubMed Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertino JR, Turnbull AD, Sullivan D, Stockman J, et al: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. The New England journal of medicine. 1999, 341 (27): 2039-2048. 10.1056/NEJM199912303412702.CrossRefPubMed
5.
go back to reference Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D'Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007, 25 (29): 4575-4580. 10.1200/JCO.2007.11.0833.CrossRefPubMed Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D'Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007, 25 (29): 4575-4580. 10.1200/JCO.2007.11.0833.CrossRefPubMed
6.
go back to reference Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, Marrero AM, Prasad M, Blumgart LH, Brennan MF: Liver resection for colorectal metastases. J Clin Oncol. 1997, 15 (3): 938-946.PubMed Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, Marrero AM, Prasad M, Blumgart LH, Brennan MF: Liver resection for colorectal metastases. J Clin Oncol. 1997, 15 (3): 938-946.PubMed
7.
go back to reference Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, Kunstlinger F, Levi F, Bismuth F: Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Annals of surgical oncology. 2001, 8 (4): 347-353. 10.1007/s10434-001-0347-3.CrossRefPubMed Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, Kunstlinger F, Levi F, Bismuth F: Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Annals of surgical oncology. 2001, 8 (4): 347-353. 10.1007/s10434-001-0347-3.CrossRefPubMed
8.
go back to reference Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D: 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): 1254-1262. 10.1002/(SICI)1097-0142(19960401)77:7<1254::AID-CNCR5>3.0.CO;2-I.CrossRefPubMed Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D: 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): 1254-1262. 10.1002/(SICI)1097-0142(19960401)77:7<1254::AID-CNCR5>3.0.CO;2-I.CrossRefPubMed
9.
go back to reference Kemeny MM, Adak S, Gray B, Macdonald JS, Smith T, Lipsitz S, Sigurdson ER, O'Dwyer PJ, Benson AB: 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 (6): 1499-1505. 10.1200/JCO.20.6.1499.CrossRefPubMed Kemeny MM, Adak S, Gray B, Macdonald JS, Smith T, Lipsitz S, Sigurdson ER, O'Dwyer PJ, Benson AB: 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 (6): 1499-1505. 10.1200/JCO.20.6.1499.CrossRefPubMed
10.
go back to reference Lygidakis NJ, 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. Hepato-gastroenterology. 1995, 42 (2): 155-161.PubMed Lygidakis NJ, 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. Hepato-gastroenterology. 1995, 42 (2): 155-161.PubMed
11.
go back to reference Lorenz M, Muller HH, Schramm H, Gassel HJ, Rau HG, Ridwelski K, Hauss J, Stieger R, Jauch KW, Bechstein WO, et al: Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen). Annals of surgery. 1998, 228 (6): 756-762. 10.1097/00000658-199812000-00006.CrossRefPubMedPubMedCentral Lorenz M, Muller HH, Schramm H, Gassel HJ, Rau HG, Ridwelski K, Hauss J, Stieger R, Jauch KW, Bechstein WO, et al: Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen). Annals of surgery. 1998, 228 (6): 756-762. 10.1097/00000658-199812000-00006.CrossRefPubMedPubMedCentral
12.
go back to reference Rudroff C, Altendorf-Hoffmann A, Stangl R, Scheele J: Prospective randomised trial on adjuvant hepatic-artery infusion chemotherapy after R0 resection of colorectal liver metastases. Langenbeck's archives of surgery/Deutsche Gesellschaft fur Chirurgie. 1999, 384 (3): 243-249.CrossRefPubMed Rudroff C, Altendorf-Hoffmann A, Stangl R, Scheele J: Prospective randomised trial on adjuvant hepatic-artery infusion chemotherapy after R0 resection of colorectal liver metastases. Langenbeck's archives of surgery/Deutsche Gesellschaft fur Chirurgie. 1999, 384 (3): 243-249.CrossRefPubMed
13.
go back to reference Wagman LD, Kemeny MM, Leong L, Terz JJ, Hill LR, Beatty JD, Kokal WA, Riihimaki DU: A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol. 1990, 8 (11): 1885-1893.PubMed Wagman LD, Kemeny MM, Leong L, Terz JJ, Hill LR, Beatty JD, Kokal WA, Riihimaki DU: A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol. 1990, 8 (11): 1885-1893.PubMed
14.
go back to reference Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O'Callaghan C, et al: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008, 26 (30): 4906-4911. 10.1200/JCO.2008.17.3781.CrossRefPubMed Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O'Callaghan C, et al: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008, 26 (30): 4906-4911. 10.1200/JCO.2008.17.3781.CrossRefPubMed
15.
go back to reference Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, 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): 1007-1016. 10.1016/S0140-6736(08)60455-9.CrossRefPubMedPubMedCentral Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, 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): 1007-1016. 10.1016/S0140-6736(08)60455-9.CrossRefPubMedPubMedCentral
16.
go back to reference Sampson M, Barrowman NJ, Moher D, Klassen TP, Pham B, Platt R, St John PD, Viola R, Raina P: Should meta-analysts search Embase in addition to Medline?. Journal of clinical epidemiology. 2003, 56 (10): 943-955. 10.1016/S0895-4356(03)00110-0.CrossRefPubMed Sampson M, Barrowman NJ, Moher D, Klassen TP, Pham B, Platt R, St John PD, Viola R, Raina P: Should meta-analysts search Embase in addition to Medline?. Journal of clinical epidemiology. 2003, 56 (10): 943-955. 10.1016/S0895-4356(03)00110-0.CrossRefPubMed
17.
go back to reference Langer Bernhard HB, Labianca Roberto, Shepherd Lois, Nitti Donato, Marsoni Silvia, Tu Dongsheng, Sargeant Ann-Marie, Fields Anthony, University of Toronto, Toronto, ON, Canada; Institute Jules Bordet, Brussels, Belgium; Ospedali Riuniti, Bergamo, Italy; NCIC CTG, Queens University, Kingston, ON, Canada; University of Padova, Padova, Italy; South Europe New Drugs Organization, Milan, Italy; Cross Cancer Inst, Edmonton, AB, Canada: Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol. 2002, 21: (abstr 592) Langer Bernhard HB, Labianca Roberto, Shepherd Lois, Nitti Donato, Marsoni Silvia, Tu Dongsheng, Sargeant Ann-Marie, Fields Anthony, University of Toronto, Toronto, ON, Canada; Institute Jules Bordet, Brussels, Belgium; Ospedali Riuniti, Bergamo, Italy; NCIC CTG, Queens University, Kingston, ON, Canada; University of Padova, Padova, Italy; South Europe New Drugs Organization, Milan, Italy; Cross Cancer Inst, Edmonton, AB, Canada: Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol. 2002, 21: (abstr 592)
18.
go back to reference Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A: 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): 1964-1970. 10.1093/annonc/mdp236.CrossRefPubMed Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A: 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): 1964-1970. 10.1093/annonc/mdp236.CrossRefPubMed
19.
go back to reference Tono T, Hasuike Y, Ohzato H, Takatsuka Y, Kikkawa N: Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: A randomized study. Cancer. 2000, 88 (7): 1549-1556. 10.1002/(SICI)1097-0142(20000401)88:7<1549::AID-CNCR8>3.0.CO;2-K.CrossRefPubMed Tono T, Hasuike Y, Ohzato H, Takatsuka Y, Kikkawa N: Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: A randomized study. Cancer. 2000, 88 (7): 1549-1556. 10.1002/(SICI)1097-0142(20000401)88:7<1549::AID-CNCR8>3.0.CO;2-K.CrossRefPubMed
20.
go back to reference Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, et al: 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 (31): 4976-4982. 10.1200/JCO.2006.06.8353.CrossRefPubMed Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, et al: 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 (31): 4976-4982. 10.1200/JCO.2006.06.8353.CrossRefPubMed
21.
go back to reference Parmar MK, Torri V, Stewart L: Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in medicine. 1998, 17 (24): 2815-2834. 10.1002/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8.CrossRefPubMed Parmar MK, Torri V, Stewart L: Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in medicine. 1998, 17 (24): 2815-2834. 10.1002/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8.CrossRefPubMed
22.
go back to reference Messori A TS, Vaiani M, et al: Survival meta-analysis of individual patient data and survial meta-analysis of published (aggregate) data: Is ther an intermediate approach between these two opposite options?. Clin Drug Invest. 2000, 20: 309-316. 10.2165/00044011-200020050-00002.CrossRef Messori A TS, Vaiani M, et al: Survival meta-analysis of individual patient data and survial meta-analysis of published (aggregate) data: Is ther an intermediate approach between these two opposite options?. Clin Drug Invest. 2000, 20: 309-316. 10.2165/00044011-200020050-00002.CrossRef
23.
go back to reference Lopez-Ladron AJS, Bernabe R, Bernardos A, Arriola E, Serrano J, Reina JJ, Gomez MA, Barneto I, Moreno-Nogueira JA, Hospital Virgen Rocio, Sevilla, Spain; Hospital JR Jimenez, Huelva, Spain; Hospital Reina Sofia, Cordoba, Spain: Observation versus postoperative chemotherapy after resection of liver metastases in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol. 2003, 22: (abstr 1497) Lopez-Ladron AJS, Bernabe R, Bernardos A, Arriola E, Serrano J, Reina JJ, Gomez MA, Barneto I, Moreno-Nogueira JA, Hospital Virgen Rocio, Sevilla, Spain; Hospital JR Jimenez, Huelva, Spain; Hospital Reina Sofia, Cordoba, Spain: Observation versus postoperative chemotherapy after resection of liver metastases in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol. 2003, 22: (abstr 1497)
24.
go back to reference Asahara T, Kikkawa M, Okajima M, Ojima Y, Toyota K, Nakahara H, Katayama K, Itamoto T, Marubayashi S, One E, et al: Studies of postoperative transarterial infusion chemotherapy for liver metastasis of colorectal carcinoma after hepatectomy. Hepato-gastroenterology. 1998, 45 (21): 805-811.PubMed Asahara T, Kikkawa M, Okajima M, Ojima Y, Toyota K, Nakahara H, Katayama K, Itamoto T, Marubayashi S, One E, et al: Studies of postoperative transarterial infusion chemotherapy for liver metastasis of colorectal carcinoma after hepatectomy. Hepato-gastroenterology. 1998, 45 (21): 805-811.PubMed
25.
go back to reference Kemeny MM, Goldberg D, Beatty JD, Blayney D, Browning S, Doroshow J, Ganteaume L, Hill RL, Kokal WA, Riihimaki DU, et al: Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. Cancer. 1986, 57 (3): 492-498. 10.1002/1097-0142(19860201)57:3<492::AID-CNCR2820570315>3.0.CO;2-M.CrossRefPubMed Kemeny MM, Goldberg D, Beatty JD, Blayney D, Browning S, Doroshow J, Ganteaume L, Hill RL, Kokal WA, Riihimaki DU, et al: Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. Cancer. 1986, 57 (3): 492-498. 10.1002/1097-0142(19860201)57:3<492::AID-CNCR2820570315>3.0.CO;2-M.CrossRefPubMed
26.
go back to reference Kokudo N, Hasegawa K, Makuuchi M: Control arm for surgery alone is needed but difficult to obtain in randomized trials for adjuvant chemotherapy after liver resection for colorectal metastases. J Clin Oncol. 2007, 25 (10): 1299-1300. 10.1200/JCO.2006.09.9069. author reply 1300CrossRefPubMed Kokudo N, Hasegawa K, Makuuchi M: Control arm for surgery alone is needed but difficult to obtain in randomized trials for adjuvant chemotherapy after liver resection for colorectal metastases. J Clin Oncol. 2007, 25 (10): 1299-1300. 10.1200/JCO.2006.09.9069. author reply 1300CrossRefPubMed
27.
go back to reference Nelson R, Freels S: Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver. Cochrane database of systematic reviews (Online). 2006, CD003770-4 Nelson R, Freels S: Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver. Cochrane database of systematic reviews (Online). 2006, CD003770-4
Metadata
Title
Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: A systematic review and meta-analysis of randomized trials
Authors
Martina Wieser
Stefan Sauerland
Dirk Arnold
Wolff Schmiegel
Anke Reinacher-Schick
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-309

Other articles of this Issue 1/2010

BMC Cancer 1/2010 Go to the issue
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