Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012, 156(2):81-92 | DOI: 10.5507/bp.2012.047

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

Bohuslav Melichar
Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic

Background: Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic-agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI).

Methods: A comprehensive review of the literature.

Results: Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity.

Conclusions: HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.

Keywords: 5-fluorouracil, colorectal carcinoma, floxuridine, hepatic arterial infusion, irinotecan, oxaliplatin

Received: December 12, 2011; Accepted: April 12, 2012; Published: June 1, 2012  Show citation

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Melichar, B. (2012). Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy? Biomedical papers, 156(2), 81-92. doi: 10.5507/bp.2012.047
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    References

    1. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. Br Med J 1993;306:752-5. Go to original source... Go to PubMed...
    2. Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Expectancy or primary chemotherapy in patients with advanced colorectal cancer: a randomized trial. J Clin Oncol 1992;10:904-11. Go to original source... Go to PubMed...
    3. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000;355:1041-7. Go to original source... Go to PubMed...
    4. Tournigand C, Andre T, Achille E, Lledo G, Flesch M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229-37. Go to original source... Go to PubMed...
    5. Hurwitz H, Febrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, E. H, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42. Go to original source... Go to PubMed...
    6. Jonker DJ, O Callaghan CJ, Karapetis C, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007;357:2040-8. Go to original source... Go to PubMed...
    7. Cunningham D, Zalcberg J, Maroun J, James R, Clarke S, Maughan TS, Vincent M, Schulz J, Gonzales Baron M, Facchini T. Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer: a review of phase II/III trials. Eur J Cancer 2002;38:478-86. Go to original source... Go to PubMed...
    8. Melichar B, Casado E, Bridgewater J, Bennouna J, Campone M, Vitek P, Delord JP, Cerman J, Salazar R, Dvorak J, Sguotti C, Urban P, Viraswami-Appanna K, Tan E, Tabernero J. Clinical activity of patupilone in patients with pretreated advanced/metastatic colon cancer: results of a phase I dose escalation trial. Br J Cancer 2011;105:1646- 53. Go to original source... Go to PubMed...
    9. Weiss L, Grundmann E, Torhorst J, Harvett F, Moberg I, Eder M, Fenoglio-Preiser CM, Napier J, Horne CHW, Lopez MJ, Shaw-Dunn RI, Sugar J, Davies JD, Day DW, Harlos JP. Haematogenous metastastic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150:195-203. Go to original source... Go to PubMed...
    10. Lee CYTM. Carcinoma of the colon and rectum: Distribution of metastatic sites, risk factors and autopsy studies. GI Cancer 1998;2:255-66.
    11. Patanaphan V, Salazar OM. Colorectal cancer: Metastatic patterns and prognosis. Southern Med J 1993;86:38-41. Go to original source... Go to PubMed...
    12. Mafune KI, Tanaka Y, Takubo K. Autopsy findings in patients with esophageal carcinoma: comparison between resection and nonresection groups. J Surg Oncol 2000;74:196-200. Go to original source... Go to PubMed...
    13. Mandard AM, Chasle J, Marnay J, Villedieu B, Bianco C, Roussel A, Elie H, Vernhes JC. Autopsy findings in 111 cases of esophageal cancer. Cancer 1981;48:329-35. Go to original source... Go to PubMed...
    14. Quint LE, Hepburn LM, Francis IR, Whyte RI, Orringer MB. Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma. Cancer 1995;76:1120-5. Go to original source... Go to PubMed...
    15. Weiss L, Harlos JP, Torhorst J, Gunthard B, Hartveit F, Svendsen E, Huang WL, Grundmann E, Eder M, Zwicknagl M, Cochrane HR, Stock D, Wright C, Horne CHW. Metastatic patterns of renal carcinoma: an analysis of 687 necropsies. J Cancer Res Clin Oncol 1988;114:605-12. Go to original source... Go to PubMed...
    16. Venook AP, Warren RS. Regional chemotherapy approaches for primary and metastatic liver tumors. Surg Oncol Clin N Amer 1996;5:411-27. Go to original source... Go to PubMed...
    17. Meta-Analysis Group in Cancer. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst 1996;88:252-8. Go to original source... Go to PubMed...
    18. Earlam S, Glover C, Davies M, Fordy C, Allen-Mersh TG. Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of life in colorectal liver metastasis patients. J Clin Oncol 1997;15:2022-9. Go to original source... Go to PubMed...
    19. Kemeny NE, Niedzwiecki D, Hollis DR, Lenz HJ, Warren RS, Naughton MJ, Weeks JC, Sigurdson ER, Herndon II JE, Zhang C, Mayer RJ. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol 2006;24:1395- 403. Go to original source... Go to PubMed...
    20. Collins JM. Pharmacologic rationale for regional drug delivery. J Clin Oncol 1984;2:498-504. Go to original source... Go to PubMed...
    21. Lin G, Lunderquist A, Hagerstrand I, Boijsen E. Postmortem examination of the blood supply and vascular pattern of small liver metastases in man. Surgery 1984;96:517-26. Go to PubMed...
    22. Lien WM, Ackerman NB. The blood supply of experimental liver metastases. II. A microcirculatory study of the normal and tumor vessels of the liver with the use of perfused silicone rubber. Surgery 1970;68:334-40. Go to PubMed...
    23. Ackerman NB. The blood supply of experimental liver metastases. IV. Changes in vascularity with increasing tumor growth. Surgery 1974;75:589-96. Go to PubMed...
    24. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol 1954;30:969-85.
    25. Sigurdson ER, Ridge JA, Kemeny N, Daly JM. Tumor and liver drug uptake following hepatic artery and portal vein infusion. J Clin Oncol 1987;5:1836-40. Go to original source... Go to PubMed...
    26. Ansfield FJ. Chemotherapy of disseminated solid tumors. J Natl Med Assoc 1962;54:658-61. Go to PubMed...
    27. Hřebabecký H, Beránek J. 5-halogeno-2, 3-cyclic sulphite isomers in the preparation of 5-halogeno nucleosides. Synthesis of 5-deoxyuridine and 5-deoxy-5-fluorouridine. Nucleic Acids Res 1978;5:1029-39. Go to original source... Go to PubMed...
    28. Goldberg JA, Kerr DJ, Watson DG, Willmott N, Bates CD, McKillop JH, McArdle CS. The pharmacokinetics of 5-fluorouracil administered by arterial infusion in advanced colorectal hepatic metastases. Br J Cancer 1990;61:913-5. Go to original source... Go to PubMed...
    29. Ensminger WD, Rosowsky A, Raso V, Levin DC, Glode M, ome S, Steele G, Frei E. A clinical-pharmacological evaluation of hepatic arterial infusion of 5-fluoro-2-deoxyuridine and 5-fluorouracil. Cancer Res 1978;38:3784-92.
    30. Armstrong RD, Diasio RB. Metabolism and biological activity of 5-deoxy-5-fluorouridine, a novel fluoropyrimidine. Cancer Res 1980;40:3333-8.
    31. Schreiber R, Raso V. Radioimmunoassay for the detection and quantitation of 5-fluorodeoxyuridine. Cancer Res 1978;38:1889-92.
    32. Bar F, Battista S, Bucchi MC, Zanon C, Grosso M, Alabiso O, Miraglia S, Cappello N, Gariboldi A, Molino G. Sorbitol removal by the metastatic liver: a predictor of systemic toxicity of intra-arterial chemotherapy in patients with liver metastases. J Hepatol 1999;30:1112-8. Go to original source... Go to PubMed...
    33. Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G. The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer 1996;73:349-59. Go to original source... Go to PubMed...
    34. Shankar A, Loizidou M, Burnstock G, Taylor I. Noradrenalin improves the tumour to normal blood flow ratio and drug delivery in a model of liver metastases. Br J Surg 1999;86:453-7. Go to original source... Go to PubMed...
    35. Dworkin MJ, Zweit J, Carnochan P, Deehan B, Allen-Mersh TG. Effect of regional angiotensin II infusion on the relationship between tumour blood flow and fluorouracil uptake in a liver metastasis animal model. Eur J Cancer 1996;32A:1580-4. Go to original source... Go to PubMed...
    36. Ansfield FJ, Ramirez G, Davis HL, Wirtanen GW, Johnson RO, Bryan GT, Manalo FB, Borden EC, Davis TE, Esmaili M. Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil. Cancer 1975;36:2413-7. Go to original source... Go to PubMed...
    37. Allen-Mersh TG, Earlam S, Fordy C, Abrams K, Houghton J. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet 1994;344:1255-60. Go to original source... Go to PubMed...
    38. Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SM. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 1987;206:685-93. Go to original source... Go to PubMed...
    39. Hohn DC, Stagg RJ, Friedman MA, Hannigan JF, Rayner A, Ignoffo RJ, Acord P, Lewis BJ. A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: The Northern California Oncology Group trial. J Clin Oncol 1989;7:1646-54. Go to original source... Go to PubMed...
    40. Kemeny N, Daly J, Reichman B, Geller N, Botet J, Oderman P. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. Ann Intern Med 1987;107:459-65. Go to original source... Go to PubMed...
    41. Kirk Martin J, O Connell MJ, Wieand HS, Fitzgibbons RJ, Mailliard JA, Rubin J, Nagorney DM, Tschetter LK, Krook JE. Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. Arch Surg 1990;125:1022-7. Go to original source... Go to PubMed...
    42. Rougier P, Laplanche A, Huguier M, Hay JM, Ollivier JM, Escat J, Salmon R, Julien M, Roullet Audy JC, Gallot D, Gouzi JL, Pailler JL, Elisa D, Lacaine F, Roos S, Rotman N, Luboinski M, Lasser P. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: Long-term results of a prospective randomized trial. J Clin Oncol 1992;10:1112-8. Go to original source... Go to PubMed...
    43. Kerr DJ, McArdle CS, Ledermann J, Taylor I, Sherlock DJ, Schlag PM, Buckels J, Mayer D, Cain D, Stephens RJ. Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicenter randomised trial. Lancet 2003;361:368-73. Go to original source... Go to PubMed...
    44. Harmantas A, Rotstein LE, Langer B. Regional versus systemic chemotherapy in the treatment of colorectal carcinoma metastatic to the liver. Is there a survival difference? Meta-analysis of the published literature. Cancer 1996;78:1639-45. Go to original source... Go to PubMed...
    45. Mocellin S, Pilati P, Lise M, Nitti D. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: The end of an era? J Clin Oncol 2007;25:5649-54. Go to original source... Go to PubMed...
    46. Lorenz M, Muller HH. Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus flurodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 2000;18:243-54. Go to original source... Go to PubMed...
    47. Samaras P, Breitenstein S, Haile SR, Stenner-Liewen F, Heinrich S, Feilchenfeldt J, Renner C, Knuth A, Pestalozzi BC, Clavien PA. Selective intra-arterial chemotherapy with floxuridine as secondor third-line approach in patients with unresectable colorectal liver metastases. Ann Surg Oncol 2011;18:1924-31. Go to original source... Go to PubMed...
    48. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000;343:905-14. Go to original source... Go to PubMed...
    49. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938- 47. Go to original source... Go to PubMed...
    50. Melichar B, Voboril Z, Cerman J, Melicharova K, Mergancova J, Voboril R, Jandik P. Survival of patients with colorectal cancer liver metastases treated by regional chemotherapy. Hepatogastroenterology 2006;53:426-34. Go to PubMed...
    51. Makela J, Kantola R, Tikkakoski T, Sinoluoto T, Leinonen S, Kiviniemi H, Laitinen S, Kairaluoma M. Superselective intra-arterial chemotherapy with mitomycin C in hepatic metastases from colorectal cancer. J Surg Oncol 1997;65:127-31. Go to original source... Go to PubMed...
    52. Link KH, Pillasch J, Formentini A, Sunelaitis E, Leder G, Safi F, Kornmann M, Beger HG. Downstaging by regional chemotherapy of non-resectable isolated colorectal liver metastases. Eur J Surg Oncol 1999;25:381-8. Go to original source... Go to PubMed...
    53. Kemeny N, Seiter K, Niedzwiecki D, Chapman D, Sigurdson E, Cohen A, Botet J, Oderman P, Murray P. A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. Cancer 1992;69:327-34. Go to original source... Go to PubMed...
    54. Kern W, Berckert B, Lang N, Stemmler J, Beykirch M, Stein J, Goecke E, Waggerhauser T, Braess J, Schalhorn A, Hiddemann W. Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer. Ann Oncol 2001;12:599- 603. Go to original source... Go to PubMed...
    55. Del Freo A, Fiorentini G, Sanguinetti F, Muttini MP, Pennucci C, Mambrini A, Pacetti P, Della Seta R, Lombardi M, Torri T, Cantore M. Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer. In Vivo 2006;20:743-6. Go to PubMed...
    56. Neyns B, van Nieuwenhove Y, Aerts M, Fontaine C, Vermeij J, Schallier D, Decoster L, De Mey J, Vandenbroucke f, Hoorens A, Delvaux G, De Greve J. Hepatic arterial infusion of oxaliplatin and L-folinic acidmodulated 5-fluorouracil for colorectal cancer liver metastases. Anticancer Res 2006;26:611-20.
    57. Boige V, Malka D, Elias D, Castaing M, De Baere T, Goere D, Dromain C, Pocard M, Ducreux M. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol 2008;15:219-26. Go to original source... Go to PubMed...
    58. Mancuso A, Giuliani R, Accetura C, Palma M, D Auria G, Cecere F, Paoluzzi L, Bezzi M, Massidda B, Cortesi E. Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer. Anticancer Res 2003;23:1917-22. Go to PubMed...
    59. Ducreux M, Ychou M, Laplanche A, Gamelin E, Lasser P, Husseini F, Quenet F, Viret F, Jacob JH, Boige V, Elias D, Delperro JR, Luboinski M. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte contre le Cancer. J Clin Oncol 2005;23:4881-7. Go to original source... Go to PubMed...
    60. Fiorentini G, Rossi S, Dentico P, Meucci F, Bonechi F, Bernardeschi P, Cantore M, Guadagni S, De Simone M. Oxaliplatin hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase I-II clinical study. Anticancer Res 2004;24:2093-6.
    61. Guthoff I, Lotspeich E, Fester C, Wallin I, Schatz M, Ehrsson H, Kornmann M. Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: Oxaliplatin pharmacokinetics and feasibility. Anticancer Res 2003;23:5203-8.
    62. Carnaghi C, Santoro A, Rimassa L, Doci R, Rosati R, Pedicini V, Gullo G, Zuradelli M, Abbadessa G, Morenghi E, Marcon I, Garassino I. The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study. Invest New Drugs 2007;25:479-85. Go to original source... Go to PubMed...
    63. Seki H, Ozaki T, Shiina M. Hepatic arterial infusion chemotherapy using fluorouracil followed by systemic therapy using oxaliplatin plus fluorouracil and leucovorin for patients with unresectable liver metastases from colorectal cancer. Cardiovasc Intervent Radiol 2009;32:679-86. Go to original source... Go to PubMed...
    64. Fiorentini G, Ricchi Lucchi S, Giovanis P, Cantore M, Guadagni S, Papiani G. Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study. Tumori 2001;87:388-90. Go to original source... Go to PubMed...
    65. Melichar B, Dvorak J, Jandik P, Touskova M, Malirova E, Mergancova J, Voboril Z. Regional administration of irinotecan in combination with 5-fluorouracil and leucovorin in patients with colorectal cancer liver metastases - a pilot experience. Hepatogastroenterology 2001;48:1721-6. Go to PubMed...
    66. Idelevich E, Greif F, Mavor E, Miller R, Kashtan H, Susmalian S, Ariche A, Brenner B, Baruch NB, Dinerman M, Shani A. Phase II study of UFT with leucovorin plus hepatic arterial infusion with irinotecan, 5-fluorouracil and leucovorin for non-resectable liver metastases of colorectal cancer. Chemotherapy 2009;55:76-82. Go to original source... Go to PubMed...
    67. van Riel JMGH, van Groeningen CJ, Kedde MA, Gall H, Leisink MA, Gruia G, Pinedo HM, van der Vijgh WJF, Giaccome G. Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Clin Cancer Res 2002;8:405-12.
    68. Guichard S, Terret C, Hennebelle I, Lochon I, Chevreau P, Fretigny E, Selves J, Chatelut E, Bugat R, Canal P. CPT-11 converting carboxylesterase and topoisomerase I activities in tumour and normal colon and liver tissues. Br J Cancer 1999;80:364-70. Go to original source... Go to PubMed...
    69. Martin RCG, Joshi J, Robbins K, Tomalty D, Bosnjakovik P, Derner M, Padr R, Rocek M, Scupchenko A, Tatum C. Hepatic intra-arterial injection of drug-eluting bead, irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study. Ann Surg Oncol 2011;18:192-8. Go to original source... Go to PubMed...
    70. Yamaguchi T, Matsumoto H, Yasutome M, Mori T, Takahashi K. Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases. Cancer Chemother Pharmacol 2011;67:629-35. Go to original source... Go to PubMed...
    71. Gallagher DJ, Capanu M, Raggio G, Kemeny N. Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis. Ann Oncol 2007;18:1995-9. Go to original source... Go to PubMed...
    72. Bouchahda M, Adam R, Giacchetti S, Castaing D, Brezault-Bonnet C, Hauteville D, Innominato PF, Focan C, Machover D, Levi F. Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer. Cancer 2009;115:4990-9. Go to original source... Go to PubMed...
    73. Chen YI, Yan Z, Wang J, Wang X, Luo J, Liu Q. Hepatic arterial infusion with oxaliplatin irinotecan and doxifluridine for unresectable liver metastases of colorectal cancer. Anticancer Res 2010;30:3045-50. Go to PubMed...
    74. Khouri C, Guiu B, Cercueil JP, Chauffert B, Ladoire S, Ghiringhelli F. Raltitrexed and oxaliplatin hepatic arterial infusion for advanced colorectal cancer: a retrospective study. Anti-Cancer Drugs 2010;21:656-61. Go to original source... Go to PubMed...
    75. van Iersel LBJ, Verlaan MR, Vahrmeijer AL, van Persijin van Meerten EL, Tijl FGJ, Sparidans RW, Gelderblom H, Kuppen PJK, Tollenaar RAEM, van de Velde CJH. Hepatic artery infusion of high-dose melphalan at reduced flow during isolated hepatic perfusion for treatment of colorectal metastases confined to the liver: a clinical and pharmacologic evaluation. Eur J Surg Oncol 2007;33:874-81. Go to original source... Go to PubMed...
    76. Fallik D, Ychou M, Jacob J, Colin P, Seitz JF, Baulieux J, Adenis A, Douillard JY, Couzigou P, Mahjoubi R, Ducreux M, Mahjoubi M, Rougier P. Hepatic arterial infusion using pirarubicin combined with systemic chemotherapy: a phase II study in patients with nonresectable liver metastases from colorectal cancer. Ann Oncol 2003;14:856- 63. Go to original source... Go to PubMed...
    77. Hartmann JT, Schmoll E, Bokemeyer C, Fety R, Lucas C, Giroux B, Schmoll HJ. Phase I pharmacological study of intra-arterially infused fotemustine for colorectal liver metastases. Eur J Cancer 1998;34:87- 91. Go to original source... Go to PubMed...
    78. Guiu B, Vincent J, Guiu S, Ladoire S, Ortega-Deballon P, Cercueil JP, Chauffert B, Ghiringhelli F. Hepatic arterial infusion of gemcitabine- oxaliplatin in a large metastasis from colon cancer. World J Gastroenterol 2010;16:1150-4. Go to original source... Go to PubMed...
    79. Cunningham D, Hurnblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337-45. Go to original source... Go to PubMed...
    80. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. 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;25:1658-64. Go to original source... Go to PubMed...
    81. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group study E3200. J Clin Oncol 2007;25:1539-44. Go to original source... Go to PubMed...
    82. Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chien CRC, Makhson A, D Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colrectal cancer. N Engl J Med 2009;360:1408-17. Go to original source... Go to PubMed...
    83. Neyns B, Aerts M, van Nieuwenhove Y, Fontaine C, de Coster L, Schallier D, Vanderauwera J, de Munck F, Vandenbroucke F, Everaert H, Meert V, de Mey J, de Ridder M, Delvaux G, de Greve J. Cetuximab with hepatic arterial infusion for chemotherapy for the treatment of colorectal cancer liver metastases. Anticancer Res 2008;28:2459-68.
    84. Camacho LH, Garcia S, Panchal AM, Lim J, Hong DS, Ng C, Madoff DC, Fu S, Gayed I, Kurzrock R. Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases. Clin Colorectal Cancer 2010;9:311-4. Go to original source... Go to PubMed...
    85. Kemeny NE, Jarnagin WR, Capanu M, Fong Y, Gerwitz AN, DeMatteo RP, DAngelica MI. Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer. J Clin Oncol 2011;29:884-9. Go to original source... Go to PubMed...
    86. Tsimberidou AM, Fu S, Ng C, Lim JA, Wen S, Hong D, Wheler J, Bedikian AY, Eng C, Wallace M, Camacho LH, Kurzrock R. A phase 1 study of hepaptic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer 2010;116:4086-94. Go to original source... Go to PubMed...
    87. Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, Chang DZ, Curcley SA, Abdalla EK, Ellis LM, Vauthey JN. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 2007;110:2761-77. Go to original source... Go to PubMed...
    88. Bouchahda M, Levi F, Adam R, Rougier P. Modern insights into hepatic arterial infusion for liver metastases from colorectal cancer. Eur J Cancer 2011;47:2681-90. Go to original source... Go to PubMed...
    89. Goere D, Deshaies I, de Baere T, Boige V, Malka D, Dumont F, Dromain C, Ducreux M, Elias D. Prolonged survival of initially unresectable hepatic colorectal cancer patients treated with hepatic arterial infusion of oxaliplatin followed by radical surgery of metastases. Ann Surg 2010;251:686-91. Go to original source... Go to PubMed...
    90. Ganeshan A, Upponi S, Hon L, Warakaulle D, Beroi R. Hepatic arterial infusion of chemotherapy: the role of diagnostic and interventional radiology. Ann Oncol 2008;19:847-51. Go to original source... Go to PubMed...
    91. Hildebrandt B, Pech M, Nicolaou A, Langrehr JM, Kurcz J, Bartels B, Miersch A, Felix R, Neuhaus P, Riess H, Dorken B, Ricke J. Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: A phase II-study and historical comparison with the surgical approach. BMC Cancer 2007;7:69. Go to original source... Go to PubMed...
    92. Arisawa Y, Sutanto-Ward E, Fortunato L, Sigurdson ER. Hepatic artery dexamethasone infusion inhibits colorectal hepatic metastases: a regional antiangiogenic therapy. Ann Surg Oncol 1995;2:114-20. Go to original source... Go to PubMed...
    93. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460-6. Go to original source... Go to PubMed...
    94. Arotcarena R, Cales V, Berthelemy P, Parent Y, Malet M, Etcharry F, Ferrari S, Pariente A. Severe sinusoidal lesions: a serious and overlooked complication of oxaliplatin-containing chemotherapy? Gastroenterol Clin Biol 2006;30:1313-6. Go to original source... Go to PubMed...
    95. Zorzi D, Lauren 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. Go to original source... Go to PubMed...
    96. Melichar B, Dvorak J, Hyspler R, Zadak Z. Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents. Chemotherapy 2005;51:336-8. Go to original source... Go to PubMed...
    97. Melichar B, Nemcová I. Eye complications of cetuximab therapy. Eur J Cancer Care 2007;16:439-43. Go to original source... Go to PubMed...
    98. Melichar B, Touskova M, Solichova D, Kralickova P, Kopecky O. CD4+ T-lymphocytopenia and systemic immune activation in patients with primary and secondary liver tumours. Scand J Clin Lab Inv 2001;61:363-70. Go to original source... Go to PubMed...
    99. Melichar B, Solichova D, Melicharova K, Malirova E, Cermanova M, Zadak Z. Urinary neopterin in patients with advanced colorectal carcinoma. Int J Biol Markers 2006;21:190-8. Go to original source...
    100. Fraker DL, Soulen M. Regional therapy of hepatic metastases. Hem Oncol Clin N Am 2002;16:947-67. Go to original source... Go to PubMed...
    101. 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;15:938-46. Go to original source... Go to PubMed...
    102. Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertion JR, Turnbull ADM, Sullivan D, Stockman J, Blumgart LH, Fong Y. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 1999;341:2039-48. Go to original source... Go to PubMed...
    103. 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;20:1499-505. Go to original source... Go to PubMed...
    104. Lorenz M, Muller HH, Schramm H, Gassel HJ, Rau HG, Ridwelski K, Hauss J, Stieger R, Jauch KW, Bechstein WO, Encke A. Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. Ann Surg 1998;228:756-62. Go to original source... Go to PubMed...
    105. Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y. Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol 2003;21:3303-9. Go to original source... Go to PubMed...
    106. Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol 2003;21:2460-5. Go to original source... Go to PubMed...
    107. Clancy TE, Dixon E, Perlis R, Sutherland FR, Zinner MJ. Hepatic arterial infusion after curative resection of colorectal cancer metastases: a meta-analysis of prospective clinical trials. J Gastrointest Surg 2005;9:198-206. Go to original source... Go to PubMed...
    108. Wieser M, Sauerland S, Arnold D, Schmiegel W, Reinacher-Schick A. Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: a systemic review and metaanalysis of randomized trials. BMC Cancer 2010;10:309. Go to original source... Go to PubMed...
    109. Leonard GD, Brenner B, N.E. K. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol 2005;23:2038-48. Go to original source... Go to PubMed...
    110. Kemeny NE, Melendez HFD, Capanu M, Paty PB, Fong Y, Schwartz LH, Jarnagin WR, Patel D, DAngelica M. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol 2009;27:3465-71. Go to original source... Go to PubMed...
    111. Martin RCG, Scoggins CR, McMasters KM. A phase II study of radiofrequency ablation of unresectable metastatic colorectal cancer with hepatic arterial infusion pump chemotherapy. J Surg Oncol 2006;93:387-93. Go to original source... Go to PubMed...
    112. Xu J, Zhong Y, Weixin N, Xinyu Q, Yanhan L, Li R, Jianhua W, Zhiping Y, Jiemin C. Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery. Ann Surg 2007;245:583-90: Go to original source... Go to PubMed...
    113. Tang JT, Wang JL, Fang JY. Meta-analysis: perioperative regional liver chemotherapy for improving survival and preventing liver metastases in patients with colorectal carcinoma. J Dig Dis 2010;11:208-14. Go to original source... Go to PubMed...
    114. Kemeny N. In defense of hepatic arterial infusion for hepatic metastases of colorectal cancer. J Natl Compr Cancer Netw 2010;8:507-9. Go to original source... Go to PubMed...
    115. Nishiofuku H, Tanaka T, Aramaki T, Boku N, Inaba Y, Sato Y, Matsuoka M, Otsuji T, Y. A, Kichikawa K. 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;9:305-10. Go to original source... Go to PubMed...

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