Localized and Locally Advanced Unresectable Adult Primary Liver Cancer
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
For selected patients with T1, T2, T3, or T4; N0; M0 disease.
Patients whose tumors are localized but unresectable due to location in the
liver, concomitant medical considerations (such as cirrhosis), or even limited
bilateral tumors, may be candidates for chemoembolization, cryosurgery,
percutaneous ethanol injection, or radiofrequency ablation for cancers smaller
than 5 cm. Survivals equivalent to resection have been reported.[1] One randomized trial in cirrhosis patients with small hepatocellular carcinomas demonstrated improved local recurrence-free survival in patients who underwent radiofrequency ablation as compared to percutaneous ethanol injections as their only form of treatment,[2][Level of evidence: 1iiDiii] but overall survival was not changed.[2][Level of evidence: 1iiA]
Clinical trials that use systemic chemotherapy, regional chemotherapy, and/or
labeled or radiolabeled antibodies have demonstrated remission of unresectable
hepatoma. Other approaches include embolization of the hepatic artery with
gelfoam powder or muscle fragments and chemotherapy, usually adriamycin. These
approaches often produce central tumor necrosis, reduction in tumor size, and
relief of pain, but the benefits are usually transient. Any interference with
arterial blood supply (including infusion chemotherapy) may be associated with
significant morbidity and is contraindicated in the presence of portal
hypertension, portal vein thrombosis, or clinical jaundice. A randomized study
of chemoembolization versus conservative treatment found no survival advantage
for chemoembolization.[3] This study was terminated early and was underpowered
to detect any but large survival differences.
Standard treatment options:
-
Radiofrequency ablation, chemoembolization, cryosurgery, or percutaneous ethanol injection: These techniques may be used in patients with small (<5 cm), localized, unresectable
tumors.[1,4-8]
-
Liver transplantation: For selected patients with localized unresectable hepatoma, particularly
patients with fibrolamellar hepatomas, liver transplantation may offer a
potentially curative treatment option.[9]
-
Chemotherapy (regional infusion of the liver): Chemotherapeutic agents may
be infused with a subcutaneous portal or implantable pump via a catheter placed
in the hepatic artery. Older studies that use standard agents have
demonstrated responses in 15% to 30% of such cases, but newer agents and
techniques (i.e., biodegradable microspheres) have been evaluated in pilot
trials,[10-12] as has regional chemotherapy with external-beam radiation
therapy.[13] Many patients are not candidates for these approaches, which
often require surgical intervention.
-
Systemic chemotherapy: Durable remissions have rarely been reported, and
no significant survival benefits have been conclusively demonstrated.
-
Surgery, chemotherapy, and radiation therapy: These modalities may be
combined in clinical trials for patients with a dominant hepatic mass and
multifocal involvement with small amounts of tumor; surgical resection, radiofrequency ablation, or
cryosurgery of the mass may be followed by hepatic infusion of the remaining
liver with chemotherapeutic agents alone or in combination with hyperthermia,
radiation, or radiation with radiosensitizers.[1] Chemotherapy plus radiation
has also been used to shrink tumors prior to resection.[14] However, the whole liver is not tolerant of large doses of radiation therapy.
-
Radiosensitizers and external-beam radiation therapy without chemotherapy: The relative radiosensitivity of
normal liver tissue compared with tumor tissue must always be considered when
radiation therapy is contemplated.[15]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized unresectable adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Zhou XD, Tang ZY: Cryotherapy for primary liver cancer. Semin Surg Oncol 14 (2): 171-4, 1998.
[PUBMED Abstract]
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Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003.
[PUBMED Abstract]
-
A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med 332 (19): 1256-61, 1995.
[PUBMED Abstract]
-
Livraghi T, Goldberg SN, Lazzaroni S, et al.: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 210 (3): 655-61, 1999.
[PUBMED Abstract]
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Tanaka K, Nakamura S, Numata K, et al.: The long term efficacy of combined transcatheter arterial embolization and percutaneous ethanol injection in the treatment of patients with large hepatocellular carcinoma and cirrhosis. Cancer 82 (1): 78-85, 1998.
[PUBMED Abstract]
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Livraghi T, Bolondi L, Lazzaroni S, et al.: Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients. Cancer 69 (4): 925-9, 1992.
[PUBMED Abstract]
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Livraghi T, Benedini V, Lazzaroni S, et al.: Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma. Cancer 83 (1): 48-57, 1998.
[PUBMED Abstract]
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Curley SA, Izzo F, Delrio P, et al.: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 230 (1): 1-8, 1999.
[PUBMED Abstract]
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Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.
[PUBMED Abstract]
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Ensminger W, Niederhuber J, Dakhil S, et al.: Totally implanted drug delivery system for hepatic arterial chemotherapy. Cancer Treat Rep 65 (5-6): 393-400, 1981 May-Jun.
[PUBMED Abstract]
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Dakhil S, Ensminger W, Cho K, et al.: Improved regional selectivity of hepatic arterial BCNU with degradable microspheres. Cancer 50 (4): 631-5, 1982.
[PUBMED Abstract]
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Choi BI, Kim HC, Han JK, et al.: Therapeutic effect of transcatheter oily chemoembolization therapy for encapsulated nodular hepatocellular carcinoma: CT and pathologic findings. Radiology 182 (3): 709-13, 1992.
[PUBMED Abstract]
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Epstein B, Ettinger D, Leichner PK, et al.: Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma. Cancer 67 (4): 896-900, 1991.
[PUBMED Abstract]
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Sitzmann JV, Abrams R: Improved survival for hepatocellular cancer with combination surgery and multimodality treatment. Ann Surg 217 (2): 149-54, 1993.
[PUBMED Abstract]
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Di Bisceglie AM, Rustgi VK, Hoofnagle JH, et al.: NIH conference. Hepatocellular carcinoma. Ann Intern Med 108 (3): 390-401, 1988.
[PUBMED Abstract]
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