Elsevier

Seminars in Oncology

Volume 37, Issue 2, April 2010, Pages 149-159
Seminars in Oncology

Regional therapies for cancers in the liver
Regional Hepatic Chemotherapies in the Treatment of Colorectal Cancer Metastases to the Liver

https://doi.org/10.1053/j.seminoncol.2010.03.005Get rights and content

The liver is the most common site of metastatic spread of colorectal cancer (CRC). Liver may be the only site of spread in as many as 30% to 40% of patients with advanced disease and can be treated with regional therapies directed toward their liver tumors. Surgery is currently the only potentially curative treatment, with a 5-year survival rate as high as 30% to 40% in selected patients. However, fewer than 25% of cases are candidates for curative resection. A number of other locoregional therapies, such as radiofrequency or microwave ablation, cryotherapy, and chemotherapy, may be offered to patients with unresectable but isolated liver metastases. However, for most patients with metastatic spread beyond the liver, systemic chemotherapy rather than regional therapy is a more appropriate option. We review the status of various regional hepatic chemotherapies in the treatment of colorectal metastases to the liver in the light of the available, published prospective, randomized trials; this discipline has not yet been properly applied to the burgeoning use of locally ablative techniques. The regional strategies reviewed include portal venous infusion (PVI) of 5-fluorouracil (5-FU), intra-arterial chemotherapy (hepatic arterial infusion [HAI]), chemoembolization, and selective internal radiation therapy (SIRT).

Section snippets

Physiology of the Liver and the Rationale for Regional Hepatic Chemotherapy

The liver is unique in that it has two blood supplies. The portal vein supplies 75% of the blood flow to the normal liver and the remaining 25% is supplied by the hepatic artery. In CRC, initial systemic spread of tumor cells occurs via the portal venous system to enter the liver. Larger metastases (>5–10 mm) obtain their blood supply predominantly from the arterial circulation, while the remaining normal hepatic parenchyma is perfused by the portal system. It is therefore rational to access

Portal Venous Infusion of Chemotherapy

PVI of chemotherapy targets micrometastases in the liver by directing chemotherapy to these deposits before they are sufficiently large to require an arterial blood supply.

The potential benefit of PVI of 5-FU as adjuvant therapy has been studied in patients with colon and rectal cancer in a series of clinical trials to determine whether the incidence of metachronous liver metastases could be reduced and survival thereby improved using this technique11, 12, 13, 14, 15, 16 (Table 1).

The first

Intrahepatic Arterial Chemotherapy

Intrahepatic arterial chemotherapy allows a high concentration of chemotherapy to be delivered directly to the site of the tumor and maximizes local concentration. HAI of chemotherapy can be considered for patients with CRC liver metastases that are not amenable to surgical resection. This field has been advanced by improvements in catheter and pump technology that allow safe, continuous, or intermittent access to the hepatic arterial vascular arcade. The catheters are inserted at laparotomy,

Chemoembolization

Chemoembolization is the process of injecting chemotherapy drugs into the artery that supplies blood to the tumor in the liver. As liver tumors are supplied with blood almost exclusively from the hepatic artery, blocking the artery with a mixture of oil and microparticles made of albumin or starch causes ischemia, reduced blood flow, and therefore more time for the cytotoxic agent to diffuse down the concentration gradient between the vascular and tumor compartments, thus increasing local

Selective Internal Radiation Therapy or Radioembolization

Radioembolization or SIRT is a means of administering radiotherapy internally to unresectable hepatic tumors in a single procedure. This technique involves the injection of resin (SIR-Spheres, Sirtex Medical Limited, Sydney, Australia) or glass microspheres (Thera-Spheres, MDS Nordion, Ottawa, Canada) that contain radioactive yttrium 90 into the hepatic artery. The advantage of radioembolization over other local techniques is that the scope of therapy is not limited by the number and

Conclusions

The current literature suggests regional therapy may have a role in combination with systemic chemotherapy, in patients with liver-only metastatic disease, either in an advanced disease setting or following resection of metastases. However, further larger randomized trials with modern systemic chemotherapy regimens will be needed to anchor HAI therapy more firmly in the therapeutic mainstream for CRC.

References (75)

  • M.M. Center et al.

    International trends in colorectal cancer incidence rates

    Cancer Epidemiol Biomarkers Prev

    (2009)
  • J. Scheele et al.

    Resection of colorectal liver metastasesWhat prognostic factors determine patient selection?

    Chirurg

    (2001)
  • J. Scheele et al.

    Resection of colorectal liver metastases

    World J Surg

    (1995)
  • K.S. Hughes et al.

    Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence

    Surgery

    (1986)
  • J. Scheele et al.

    Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history

    Br J Surg

    (1990)
  • W.D. Ensminger et al.

    A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil

    Cancer Res

    (1978)
  • N. Wolmark et al.

    Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02

    J Clin Oncol

    (1990)
  • I. Taylor et al.

    A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer

    Br J Surg

    (1985)
  • U. Laffer et al.

    Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial

    Int J Colorectal Dis

    (2008)
  • Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer

    Lancet

    (1995)
  • R.D. James et al.

    Randomized clinical trial of adjuvant radiotherapy and 5-fluorouracil infusion in colorectal cancer (AXIS)

    Br J Surg

    (2003)
  • Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies

    J Natl Cancer Inst

    (1997)
  • R. Labianca et al.

    A randomised trial of intraportal (IP) versus systemic (SY) versus IP + SY adjuvant chemotherapy in patients with resected Dukes B-C colon carcinoma [abstract]

    Proc Am Soc Clin Oncol

    (1999)
  • R. Labianca et al.

    Randomized trial of intraportal and/or systemic adjuvant chemotherapy in patients with colon carcinoma

    J Natl Cancer Inst

    (2004)
  • N. Kemeny et al.

    A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer

    Cancer

    (1992)
  • D.C. Hohn et al.

    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)
  • A.E. Chang et al.

    A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases

    Ann Surg

    (1987)
  • L.D. Wagman et al.

    A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver

    J Clin Oncol

    (1990)
  • J.K. Martin et al.

    Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancerA randomized trial

    Arch Surg

    (1990)
  • P. Rougier et al.

    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)
  • M. Lorenz et al.

    Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma

    J Clin Oncol

    (2000)
  • N. Kemeny et al.

    Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinomaA randomized trial

    Ann Intern Med

    (1987)
  • N.E. Kemeny et al.

    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)
  • S. Mocellin et al.

    Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era?

    J Clin Oncol

    (2007)
  • S. Mocellin et al.

    Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer

    Cochrane Database Syst Rev

    (2009)
  • N. Kemeny et al.

    Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer

    J Clin Oncol

    (2001)
  • N. Kemeny 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)
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