Skip to main content
Top
Published in: Clinical and Translational Oncology 11/2015

01-11-2015 | Research Article

Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases

Authors: W.-G. Qiang, L.-R. Shi, X.-D. Li, Q.-Q. Wu, J.-M. Zhao, L.-J. Chen, Y. Yang, J. Wu, M. Ji, C.-P. Wu

Published in: Clinical and Translational Oncology | Issue 11/2015

Login to get access

Abstract

Backgrounds

The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting.

Methods

This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B).

Results

The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2.

Conclusions

HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.
Literature
2.
go back to reference Sperling J, Schafer T, Ziemann C, Benz-Weiber A, Kollmar O, Schilling MK, et al. Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases. Clin Exp Metastasis. 2012;29(2):91–9. doi:10.1007/s10585-011-9432-6.CrossRefPubMed Sperling J, Schafer T, Ziemann C, Benz-Weiber A, Kollmar O, Schilling MK, et al. Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases. Clin Exp Metastasis. 2012;29(2):91–9. doi:10.​1007/​s10585-011-9432-6.CrossRefPubMed
3.
go back to reference Teker F, Demirag G, Erdem D, Kemal Y, Yucel I. Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies. J BUON. 2015;20(2):443–51.PubMed Teker F, Demirag G, Erdem D, Kemal Y, Yucel I. Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies. J BUON. 2015;20(2):443–51.PubMed
4.
go back to reference Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, et al. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer. 2015;15(1):428. doi:10.1186/s12885-015-1430-7.PubMedCentralCrossRefPubMed Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, et al. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer. 2015;15(1):428. doi:10.​1186/​s12885-015-1430-7.PubMedCentralCrossRefPubMed
5.
go back to reference Landry JC, Feng Y, Prabhu RS, Cohen SJ, Staley CA, Whittington R, et al. Phase II trial of preoperative radiation with concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes ECOG-ACRIN cancer research group E3204. Oncologist. 2015. doi:10.1634/theoncologist.2015-0106.PubMedCentralPubMed Landry JC, Feng Y, Prabhu RS, Cohen SJ, Staley CA, Whittington R, et al. Phase II trial of preoperative radiation with concurrent Capecitabine, Oxaliplatin, and Bevacizumab followed by surgery and postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes ECOG-ACRIN cancer research group E3204. Oncologist. 2015. doi:10.​1634/​theoncologist.​2015-0106.PubMedCentralPubMed
6.
go back to reference Ogata Y, Matono K, Tsuda H, Ushijima M, Uchida S, Akagi Y, et al. Randomized phase II study of 5-fluorouracil hepatic arterial infusion with or without antineoplastons as an adjuvant therapy after hepatectomy for liver metastases from colorectal cancer. PLoS One. 2015;10(3):e0120064. doi:10.1371/journal.pone.0120064.PubMedCentralCrossRefPubMed Ogata Y, Matono K, Tsuda H, Ushijima M, Uchida S, Akagi Y, et al. Randomized phase II study of 5-fluorouracil hepatic arterial infusion with or without antineoplastons as an adjuvant therapy after hepatectomy for liver metastases from colorectal cancer. PLoS One. 2015;10(3):e0120064. doi:10.​1371/​journal.​pone.​0120064.PubMedCentralCrossRefPubMed
7.
go back to reference Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658–64. doi:10.1200/JCO.2006.08.1620.CrossRefPubMed Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658–64. doi:10.​1200/​JCO.​2006.​08.​1620.CrossRefPubMed
8.
go back to reference Liu W, Song QK, Xing BC. A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases. Int J Colorectal Dis. 2015. doi:10.1007/s00384-015-2246-2. Liu W, Song QK, Xing BC. A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases. Int J Colorectal Dis. 2015. doi:10.​1007/​s00384-015-2246-2.
9.
go back to reference Tanaka T, Arai Y, Inaba Y, Matsueda K, Aramaki T, Takeuchi Y, et al. Radiologic placement of side-hole catheter with tip fixation for hepatic arterial infusion chemotherapy. J Vasc Interv Radiol. 2003;14(1):63–8.CrossRefPubMed Tanaka T, Arai Y, Inaba Y, Matsueda K, Aramaki T, Takeuchi Y, et al. Radiologic placement of side-hole catheter with tip fixation for hepatic arterial infusion chemotherapy. J Vasc Interv Radiol. 2003;14(1):63–8.CrossRefPubMed
10.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefPubMed
11.
go back to reference Breugom AJ, van Gijn W, Muller EW, Berglund A, van den Broek CB, 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(4):696–701. doi:10.1093/annonc/mdu560.CrossRefPubMed Breugom AJ, van Gijn W, Muller EW, Berglund A, van den Broek CB, 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(4):696–701. doi:10.​1093/​annonc/​mdu560.CrossRefPubMed
12.
go back to reference Komori H, Beppu T, Sakamoto Y, Miyamoto Y, Hayashi H, Imai K, et al. Irinotecan plus S-1 followed by hepatectomy for a patient with initially unresectable colorectal liver metastases, who showed severe drug rash with oxaliplatin plus 5-FU and Leucovorin (FOLFOX). Case Rep Gastrointest Med. 2014:2014;906759. doi:10.1155/2014/906759.PubMedCentralPubMed Komori H, Beppu T, Sakamoto Y, Miyamoto Y, Hayashi H, Imai K, et al. Irinotecan plus S-1 followed by hepatectomy for a patient with initially unresectable colorectal liver metastases, who showed severe drug rash with oxaliplatin plus 5-FU and Leucovorin (FOLFOX). Case Rep Gastrointest Med. 2014:2014;906759. doi:10.​1155/​2014/​906759.PubMedCentralPubMed
13.
15.
go back to reference Lainas P, Camerlo A, Conrad C, Shivathirthan N, Fuks D, Gayet B. Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: is it feasible and reasonable? Surgery. 2015. doi:10.1016/j.surg.2015.02.003.PubMed Lainas P, Camerlo A, Conrad C, Shivathirthan N, Fuks D, Gayet B. Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: is it feasible and reasonable? Surgery. 2015. doi:10.​1016/​j.​surg.​2015.​02.​003.PubMed
16.
go back to reference Vigano L, Capussotti L, Lapointe R, Barroso E, Hubert C, Giuliante F, et al. Early recurrence after liver resection for colorectal metastases: risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6025 patients. Ann Surg Oncol. 2014;21(4):1276–86. doi:10.1245/s10434-013-3421-8.CrossRefPubMed Vigano L, Capussotti L, Lapointe R, Barroso E, Hubert C, Giuliante F, et al. Early recurrence after liver resection for colorectal metastases: risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6025 patients. Ann Surg Oncol. 2014;21(4):1276–86. doi:10.​1245/​s10434-013-3421-8.CrossRefPubMed
17.
go back to reference Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamata H, Koisumi J. Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer. Surg Today. 2013;43(10):1088–94. doi:10.1007/s00595-012-0416-1.CrossRefPubMed Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamata H, Koisumi J. Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer. Surg Today. 2013;43(10):1088–94. doi:10.​1007/​s00595-012-0416-1.CrossRefPubMed
18.
go back to reference Bolton JS, O’Connell MJ, Mahoney MR, Farr GH Jr, Fitch TR, Maples WJ, et al. Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic to the liver: a North Central Cancer Treatment Group (NCCTG) phase II study, 92-46-52. Clin Colorectal Cancer. 2012;11(1):31–7. doi:10.1016/j.clcc.2011.03.029.PubMedCentralCrossRefPubMed Bolton JS, O’Connell MJ, Mahoney MR, Farr GH Jr, Fitch TR, Maples WJ, et al. Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic to the liver: a North Central Cancer Treatment Group (NCCTG) phase II study, 92-46-52. Clin Colorectal Cancer. 2012;11(1):31–7. doi:10.​1016/​j.​clcc.​2011.​03.​029.PubMedCentralCrossRefPubMed
20.
go back to reference Arai Y, Ohtsu A, Sato Y, Aramaki T, Kato K, Hamada M, et al. Phase I/II study of radiologic hepatic arterial infusion of fluorouracil plus systemic irinotecan for unresectable hepatic metastases from colorectal cancer: Japan Clinical Oncology Group Trial 0208-DI. J Vasc Interv Radiol. 2012;23(10):1261–7. doi:10.1016/j.jvir.2012.06.031.CrossRefPubMed Arai Y, Ohtsu A, Sato Y, Aramaki T, Kato K, Hamada M, et al. Phase I/II study of radiologic hepatic arterial infusion of fluorouracil plus systemic irinotecan for unresectable hepatic metastases from colorectal cancer: Japan Clinical Oncology Group Trial 0208-DI. J Vasc Interv Radiol. 2012;23(10):1261–7. doi:10.​1016/​j.​jvir.​2012.​06.​031.CrossRefPubMed
21.
go back to reference Kemeny N, Jarnagin W, Paty P, Gonen M, Schwartz L, Morse M, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005;23(22):4888–96. doi:10.1200/JCO.2005.07.100.CrossRefPubMed Kemeny N, Jarnagin W, Paty P, Gonen M, Schwartz L, Morse M, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005;23(22):4888–96. doi:10.​1200/​JCO.​2005.​07.​100.CrossRefPubMed
22.
go back to reference Boige V, Malka D, Elias D, Castaing M, De Baere T, Goere D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15(1):219–26. doi:10.1245/s10434-007-9581-7.CrossRefPubMed Boige V, Malka D, Elias D, Castaing M, De Baere T, Goere D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15(1):219–26. doi:10.​1245/​s10434-007-9581-7.CrossRefPubMed
23.
go back to reference Nishiofuku H, Tanaka T, Aramaki T, Boku N, Inaba Y, Sato Y, et al. Hepatic arterial infusion of 5-fluorouracil for patients with liver metastases from colorectal cancer refractory to standard systemic chemotherapy: a multicenter, retrospective analysis. Clin Colorectal Cancer. 2010;9(5):305–10. doi:10.3816/CCC.2010.n.044.CrossRefPubMed Nishiofuku H, Tanaka T, Aramaki T, Boku N, Inaba Y, Sato Y, et al. Hepatic arterial infusion of 5-fluorouracil for patients with liver metastases from colorectal cancer refractory to standard systemic chemotherapy: a multicenter, retrospective analysis. Clin Colorectal Cancer. 2010;9(5):305–10. doi:10.​3816/​CCC.​2010.​n.​044.CrossRefPubMed
24.
go back to reference Sofocleous CT, Garcia AR, Pandit-Taskar N, Do KG, Brody LA, Petre EN, et al. Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy. Clin Colorectal Cancer. 2014;13(1):27–36. doi:10.1016/j.clcc.2013.11.010.CrossRefPubMed Sofocleous CT, Garcia AR, Pandit-Taskar N, Do KG, Brody LA, Petre EN, et al. Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy. Clin Colorectal Cancer. 2014;13(1):27–36. doi:10.​1016/​j.​clcc.​2013.​11.​010.CrossRefPubMed
25.
go back to reference 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. doi:10.1245/s10434-013-3217-x.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. doi:10.​1245/​s10434-013-3217-x.CrossRefPubMed
Metadata
Title
Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases
Authors
W.-G. Qiang
L.-R. Shi
X.-D. Li
Q.-Q. Wu
J.-M. Zhao
L.-J. Chen
Y. Yang
J. Wu
M. Ji
C.-P. Wu
Publication date
01-11-2015
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 11/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1317-8

Other articles of this Issue 11/2015

Clinical and Translational Oncology 11/2015 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