Cancer Treatment

Gleevec for liver cancer

While there is resonable theoretical basis for the use of Gleevec for HCC, there is littel supporting clicnial data. A recent pahse II study revealed that fifteen patients, median age 58 years, were enrolled and treated with imatinib. Most, or 7, patients had hepatitis B virus as a risk factor for HCC, followed by hepatitis C virus in 3 patients. Metastatic disease (American Joint Committee on Cancer stage IV) was noted in 13 patients and locally advanced (stage III) in the remainder. The median dose-level of imatinib was 500 mg/d. Two patients had stable disease lasting more than 2 months. The remainder progressed within 2 months of initiation of imatinib. No grade 3 or 4 hematologic toxicity was observed. Two patients had grade 3 elevated liver function tests during treatment; otherwise, there was no other grade 3 or 4 nonhematologic toxicity noted.
Although toxicities were tolerable, imatinib as a monotherapy for the treatment of unresectable HCC has little, if any, significant efficacy.

While EGFR analysis may allow selecting patients who will respond better, this remains to be proven.

Lin, Albert Y. MD et al, Phase II Study of Imatinib in Unresectable Hepatocellular Carcinoma. American Journal of Clinical Oncology. 31(1):84-88, February 2008.

S D Ryder Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults Gut 2003;52:iii1

Radiofrequency ablation for the liver

Radiofrequency ablation (RFA) is a thermoablative technique which destroys tissue by heating cancer cells to temperatures exceeding 60°C. In RFA, temperature changes are induced using high-frequency alternating current applied via an electrode or electrodes placed within the tissue to generate ionic agitation. RFA can be applied percutaneously, laparoscopically or intraoperatively.

Percutaneous ablation is a commonly used modality of tratment when resection is not possible for HCC. Other local modalities are radiofrequency ablation or chemo embolization. Microwave coagulation therapy, one of the thermal ablation therapies now available, has been used in the treatment of liver metastases. To date, at least seven series have been published in the English-language literature  in which the results of microwave coagulation therapy of hepatic metastases have been described. However, these results were narrowly focused preliminary studies: a few clinical patient trials, principally as assessments of feasibility, safety, and short-term efficacy. Although the preliminary results are promising, few articles concerning the effect of microwave ablation on survival have been published. This is even more true in the setting of metastatic cancer.

A R Gillams
Liver ablation therapy
Br. J. Radiol., September 1, 2004; 77(921): 713 - 723.

P. Liang, B. Dong, X. Yu, Y. Yang, D. Yu, L. Su, Q. Xiao, and L. Sheng
Prognostic Factors for Percutaneous Microwave Coagulation Therapy of Hepatic Metastases
Am. J. Roentgenol., November 1, 2003; 181(5): 1319 - 1325.

http://www.nice.org.uk/nicemedia/pdf/ip/IPG092guidance.pdf

Decitabine and epigenetic therapy for solid cancers

Lay search: Decitabine is being studies for :epigenetic" therapy of solid cacners.

Genes involved in all aspects of tumor development and growth can become aberrantly methylated in tumor cells, including genes involved in apoptosis and cell cycle regulation. Decitabine, 2´-deoxy-5-azacytidine, can inhibit DNA methyltransferases and reverse epigenetic silencing of aberrantly methylated genes. Nucleoside DNA methyltransferase inhibitors, such as decitabine, have been reported to have antitumor activity, especially against hematologic malignancies. Such demethylating agents have been proposed to reactivate tumor suppressor genes aberrantly methylated in tumor cells, leading to inhibition of tumor growth.

Currenlty Decitabine is FDA approved for myedlodysplaisa. Because of the aforementioned emchanism of action, there is interest in studying it in colorectal and oterh solid cancers. Decitabine has been studied in several phase II trials for solid tumours as well as in different types of leukaemia. The drug has been shown to have very limited efficacy against solid tumours. However, decitabine exhibits higher activity for the treatment of haematological malignancies.

Robert Brown, Jane A Plumb Demethylation of DNA by decitabine in cancer chemotherapyExpert Review of Anticancer Therapy August 2004, Vol. 4, No. 4, Pages 501-510

Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.

Kantarjian H, O'Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.

http://jco.ascopubs.org/cgi/reprint/JCO.2004.01.947v1.pdf

Adis Decitabine: 2'-Deoxy-5-azacytidine, Aza dC, DAC, Dezocitidine, NSC 127716. R&D Profile Drugs in R & D. 4(6):352-358, 2003.

Jean-Pierre J. Issa DNA Methylation as a Therapeutic Target in Cancer Clinical Cancer Research 13, 1634-1637, March 15, 2007.

Thalidomide for liver cancer

Lay Summary: Thalidomide can get an occasional response in hepatocellular cancer.

Thalidomide has poorly understood mechanisms of action, and it might exert its therapeutic properties through antiangiogenic activity and modulation of cytokines, including tumor necrosis factor-, interferon, interleukins 10 and 12, cyclooxygenase-2, and nuclear factor B. Several studies have examined the efficacy and toxicity of thalidomide in HCC . Hsu and colleagues conducted a study using thalidomide in 68 HCC patients. Of the 63 evaluable patients, one complete and three partial responses were seen, for a response rate of 6.3% (95% CI, 0%–12.5%). Ten patients had a dramatic decrease in their AFP levels. Interestingly, all responders received thalidomide at 300 mg or less per day. In another study, involving 99 patients with advanced HCC, responses were seen in six patients in response to single-agent thalidomide]. Several recent phase II studies from the U.S. have examined the use of thalidomide either as a single agent or in combination with epirubicin or interferon and have shown limited activity in HCC. Fatigue and somnolence were the most common side effects associated with thalidomide administration.

Eleutherakis-Papaiakovou V, Bamias A, Dimopoulos MA. Thalidomide in cancer medicine. Ann Oncol 2004;15:1151–1160.
Hsu C, Chen CN, Chen LT et al. Low-dose thalidomide treatment for advanced hepatocellular carcinoma. Oncology 2003;65:242–249
Wang TE, Kao CR, Lin SC et al. Salvage therapy for hepatocellular carcinoma with thalidomide. World J Gastroenterol 2004;10:649–653.
Lin AY, Brophy N, Fisher GA et al. Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma. Cancer 2005;103:119–125.
Patt YZ, Hassan MM, Lozano RD et al. Thalidomide in the treatment of patients with hepatocellular carcinoma: a phase II trial. Cancer 2005;103:749–755.
Zhu AX, Fuchs CS, Clark JW et al. A phase II study of epirubicin and thalidomide in unresectable or metastatic hepatocellular carcinoma. The Oncologist 2005;10:392–398.
Schwartz JD, Sung M, Schwartz M et al. Thalidomide in advanced hepatocellular carcinoma with optional low-dose interferon-alpha2a upon progression. The Oncologist 2005;10:718–727.

Liver transplantation for liver cancer

Lay Summary: Some people with liver cancer can be cured by liver transplantation.

Among the curative therapies for HCC, LT has gained wider acceptance as improvements in crude survival and recurrence-free survival have been demonstrated in selected cases with curative potential. LT has the advantage of resecting the whole liver, including the HCC, and potentially removing undiagnosed synchronous HCC, daughter HCC, and hepatic micro-invasion. Moreover, LT treats cirrhosis and therefore protects the patient against future complications of cirrhosis and development of a second HCC. The main drawbacks of LT are the high incidence of posttransplant recurrence, which is enhanced by immunosuppressive agents,[12] and the shortage of liver grafts, which leads to long waiting times on the LT list. The doubling time of HCC is approximately 6 months; thus, a significant number of patients become nontransplantable during the interval between evaluation and acceptance for LT and availability of a graft, leading to a significant drop-out rate (due to death) that is variable across centers and responsible for variable management strategies across centers. This factor should be included in all studies comparing results of LT to liver resection for HCC (intent-to-treat analysis).

To date, no randomized study has been done to compare results of resection vs LT for HCC and, therefore, no definite conclusion about which treatment offers the best outcome can be made. Such a study is unlikely, however, because recent, good retrospective papers have reported better results for LT compared with resection in selected cases. There are no guidelines. The consensus of teh literature is that in selected cases liver transplantation is medically appropriate.

Bigourdan JM, Jaeck D, Meyer N, et al. Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation. Liver Transpl. 2003;9:513-520.

Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434-1440. Abstract

Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-699.

SIRT for hepatic mets of colon cancer

Lay Sammary: SIRT is a new promising treatment for liver cancer or metastases to the liver. Most insurers consider it investigational and active research is ongoing.

SIRT -- a therapy that consists of millions of microscopic, radioactive glass microspheres (20-30 microns diameter) -- is infused into the arteries that feed inoperable liver tumors or metastatic cancer to the liver, bathing the malignancy in high levels of extremely localized radiation. In some studies of highly selected pateints the response rates and stabilization rates ranged between 20-40 percent. Selective internal radiation therapy (SIRT) is used to treat non-resectable hepatic metastases secondary to colorectal cancer, usually in combination with hepatic arterial chemotherapy. The standard method of treatment for patients with liver metastases from colorectal cancer is surgical resection, but fewer than 10% of patients are suitable for operation. For patients with non-resectable hepatic metastases, treatment options include systematic chemotherapy, radiotherapy, cryotherapy, alcohol injection and laser photocoagulation. Radioactive spheres are injected using a syringe into the hepatic artery via a trans-femoral catheter or a permanently implanted port with a catheter to the hepatic artery.

Currently 2 commercial forms of yttrium-90 microspheres are available: TheraSpheres® (Theragenics;Atlanta, GA) and SIR-Spheres® (Sirtex Medical Limited; Lake Forest, IL). Non-commercial forms are used mostly outside the United States. Note also that the U.S. Food and Drug Administration (FDA) granted a premarket approval of SIR-Spheres®, for use in combination with 5-floxuridine (5-FUDR) chemotherapyby HAI, to treat unresectable hepatic metastases from colorectal cancer. Microspheres are taken up by the microvasculature within the liver. A limited randomized trial suggests that this treatment is well tolerated. There are also trials that suggest incresed survival but these are not blinded randomized trials. A Harvard Pilgrim 2005 TEC Assessment found the procedure to be investigational. FDA approval of a technology does not make its apllications automaitcally not investigational and unlike medications is not binding on a plan. The most recent guidelines on this subject is from 2006 and is referenced.

It is beng investigated in a phase II trial, NCT00511862,TheraSphere for the Treatment of Liver Metastases: An Open Label Trial of TheraSphere in Patients With Liver Metastases From Primary Colorectal Cancer, Neuroendocrine Cancer or Non-Colorectal/Non-Neuroendocrine Cancer .

NICE Guidelines - http://www.nice.org.uk/pdf/ip/IPG093guidance.pdf

Australian Guidelines - http://www.tripdatabase.com/spider.html?itemid=282101

Guy Van Hazel et al, Randomised phase 2 trial of SIR-Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer J. Surg. Oncol. Volume 88, Issue 2 , Pages 78 - 85

W. Oyen, L Bodei, F Giammarile, H. Maecke, J Tennvall, M Luster, and B Brans
Targeted therapy in nuclear medicine--current status and future prospects
Ann. Onc., April 13, 2007; (2007)

L . Jiao , T . Szyszko , A . Al-Nahhas , P . Tait , R . Canelo , G . Stamp , H . Wasan , C . Lowdell , R . Philips , A . Thillainayagam Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours . 
European Journal of Surgical Oncology , Volume 33 , Issue 5 , Pages 597 - 602, 2007

D. L. Bartlett, J. Berlin, G. Y. Lauwers, W. A. Messersmith, N. J. Petrelli, and A. P. Venook
Chemotherapy and Regional Therapy of Hepatic Colorectal Metastases: Expert Consensus Statement
Ann. Surg. Oncol., October 1, 2006; 13(10): 1284 - 1292.

Oncotech chemosensitivity and chemoresistance assays

Lay Summary: Chemosensitivity assays are controversial but most experts believe that they do not reliably assist in selecting chemotherapy. There is more evidence for chemoresistance assays but this also remains disputed.

Oncotech ER is a form of chemosensitivity testing, or rather, a modification that tests resistance to chemo rather than sensitivity. The recent article by Schrag et al1 criticized the field of chemosensitivity and drug resistance, concluding that these types of in vitro assays are not yet ready for prime time. The panel of authors attempted to present evidence that in vitro drug response assays should not be used clinically. This issue was first addressed by an exhaustive Medicare Coverage Advisory Committee (MCAC) in 1999. A panel of physicians selected by the Department of Health and Human Services reviewed hundreds of articles from the literature and heard two days of testimony by experts in the field in an open hearing. The panel voted unanimously that although chemosensitivity assays should not be covered, drug resistance assays should be paid for. This became a casue celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The Amreican Society of Clnical Oncology vigorously objected and recommended: "
The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient's health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority."  I believe that the So. California branch of ASCO disssented from this recommendation, see http://weisenthal.org/medicareletter.pdf.

The Extreme Drug Resistance Assay (EDR) Assay is a laboratory test performed on a patient's tumor cells. This lab test is claimed to determine the probability of a tumor's resistance to a specific chemotherapy drug. If the tumor cells grow in the presence of very high concentrations of chemotherapy drug, then the cancer cells are considered resistant to that drug.

Drug sensitivity and resistance assays have been examined for their potential utility in ovarian cancer by a number of clinical investigators. Unfortunately, analysis of these studies has suffered greatly from the absence of an appropriate control population. The majority of these trials have compared the survival of individuals whose treatment was selected by a particular assay with a historical/retrospective patient group treated at the same institution. A report in the Gynecologic Cancer session described an important attempt by investigators in Europe to directly address the value of the adenosine triphosphate (ATP)-based tumor chemosensitivity assay, by randomizing patients with platinum-resistant ovarian cancer (n = 180) to either "assay-directed therapy" or the treatment of the "physician's choice". The objective response rate was 40.5% for the assay-directed group vs 31.5% for the physician's choice of treatment. Progression-free survival (intention-to-treat analysis) was 104 days in the assay-directed vs 93 days in the physician's choice groups. In addition, there was no difference in overall survival between the strategies. This study provides support for the conclusion that the ATP-based tumor chemosensitivity assay is not superior to physician's choice in the selection of chemotherapy in women with platinum-resistant ovarian cancer.Some experts claim that resistance assays are different from chemosensitivity assays and Medicare does cover them. However, this distinction has not been sufficiently demonstrated and most expersts vigorously dispute this.

In conclusion, the technologies and the questions that they raise are quite different. It Oncotech Sensitivy testing not yet been  recommended by professional societies and gudielines pending completion of a phase III trial. With Oncotech ER the situation is as described above.

Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology technology assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22 : 3631 -3638, 2004

John P. Fruehauf In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3641-3643

P. Hwu, A. Y. Bedikian, and E. A. Grimm
Challenges of chemosensitivity testing.
Clin. Cancer Res., September 15, 2006; 12(18): 5258 - 5259.

M. Markman Chemosensitivity and Chemoresistance Testing
J. Clin. Oncol., October 10, 2005; 23(29): 7363 - 7364.

R. Nagourney Chemosensitivity and Resistance Assays: A Systematic Review?
J. Clin. Oncol., May 20, 2005; 23(15): 3640 - 3641.

J. P. Fruehauf and D. S. Alberts
In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins
J. Clin. Oncol., May 20, 2005; 23(15): 3641 - 3643.
 
H. S. Wieand
Chemotherapy Sensitivity and Response Assays: Are the ASCO Guidelines for Clinical Trial Design Too Restrictive?
J. Clin. Oncol., May 20, 2005; 23(15): 3643 - 3644.
 
M. Castro Resisting a Fundamentalist Policy
J. Clin. Oncol., May 20, 2005; 23(15): 3645 - 3646.

Yttrium-90 spheres fo HCC

Lay Summary: Theraspheres are being investigated for liver cancer and colon cancer metastases. It is considered investigtionanl at this time.

TheraSphere -- a therapy that consists of millions of microscopic, radioactive glass microspheres (20-30 microns diameter) -- is infused into the arteries that feed inoperable liver tumors, bathing the malignancy in high levels of extremely localized radiation. In some studies of highly selected pateints the response rates and stabilization rates ranged between 20-40 percent. No survival benefit has been demonstrated adn the technique is still in phase II studies.

This therapy is currently considered to be investigational. A recent guideline states: "radio-labeled Yttrium glass beads, radio-labeled lipiodol or immunotherapy cannot be recommended as standard therapy for advanced HCC outside clinical trials".

L. A. Dawson
Hepatic Arterial Yttrium 90 Microspheres: Another Treatment Option for Hepatocellular Carcinoma
J. Vasc. Interv. Radiol., February 1, 2005; 16(2): 161 - 164.

R. Salem, R. J. Lewandowski, B. Atassi, S. C. Gordon, V. L. Gates, O. Barakat, Z. Sergie, C.-Y. O. Wong, and K. G. Thurston
Treatment of Unresectable Hepatocellular Carcinoma with Use of 90Y Microspheres (TheraSphere): Safety, Tumor Response, and Survival
J. Vasc. Interv. Radiol., December 1, 2005; 16(12): 1627 - 1639

Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005 Nov;42(5):1208-36. [322 references]

Liver Cancer/TACE

The prognosis for patients with unresectable hepatocellular carcinoma (HCC) tumors is extremely poor. Even in the case of small nodular lesions detected by US screening, patients receiving no treatment showed a mean 3-year survival rate of 12%.. Transcatheter arterial chemoembolization (TACE), most frequently performed by intra-arterially injecting an infusion of antineoplastic agents mixed with iodized oil (Lipiodol), has been extensively used in the treatment of large HCC tumors. However, although massive tumor necrosis can be demonstrated in most cases, a complete necrosis of the tumor has rarely been achieved with TACE, since residual tumor can be found in a non-negligible number of the treated lesions. It si, however, useful prior to liver transplantation.
TACE was found mostly effective in nodules less than 4 cm in diameter, with a thick tumor capsule. In fact, small, encapsulated HCC are almost completely fed by hepatic arterial blood and therefore highly responsive to hepatic arterial embolization. On the contrary, in unencapsulated tumors or in tumors showing extracapsular invasion of neoplastic cells, TACE often fails to induce complete necrosis since tumor cells, either unimpeded by the absence of a capsule or spreading across the capsule itself, invade the adjacent liver parenchyma, thus obtaining additional blood supply from the sinusoidal portal system.
Large HCC lesions can be more effectively treated with combined TACE and PEI. In fact, alcohol diffusion is easier after the occurrence of the necrotic changes produced by TACE, thus allowing the intranodular injection of larger amounts of ethanol. Moreover, after arterial embolization, the normal wash-out of the injected ethanol is more difficult in the tumorous area, resulting in longer retention of the substance. The combination of TACE and PEI seems to be a highly effective treatment for large HCC also in the instances when daughter nodules are associated with a main tumor. The presence of the capsule significantly enhances the chances of success and should be considered an important requirement when selecting patients to be submitted to TACE and PEI.
According to available literature, chemoembolization (TACE) may be indicated for symptomatic treatment of functional neuroendocrine cancers (i.e., carcinoid tumors and pancreatic endocrine tumors) involving the liver, in persons with adequate hepatic function (bilirubin < 2 mg/dl, absence of ascites; no portal vein occlusion; and tumor involvement of < 65 % of liver). For carcinoid tumors, TACE is indicated only in persons who have failed systemic therapy with octreotide to control carcinoid syndrome (e.g., debilitating flushing, wheezing and diarrhea). The safety and effectiveness of more than 4 TACE procedures is unknown.
For unresectable, primary HCC, TACE is indicated in persons with small encapsulated nodules (less than 4 cm in diameter), no evidence of extrahepatic metastases, and with adequate hepatic (serum bilirubin concentration < 2.9 mg/dl) and renal function (serum creatinine < 2.0 mg/dl).

Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol. 2002;13(9 Pt 2):S211-S221.
Oliveri RS, Gluud C. Transcatheter arterial embolisation and chemoembolisation for hepatocellular carcinoma (Protocol for Cochrane Review). Cochrane Database Systematic Rev. 2004;2:CD004787.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003;37(2):429-442.
Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-analysis of randomized controlled trials. Radiology. 2002;224(1):47-54.

Chemoembolization

Lay Summary: TACE is often used for hepatocellular carcinoma and neuroendocrine cancers of the liver.

This technique takes advantage of the fact that HCC is a very vascular (contains many blood vessels) tumor and gets its blood supply exclusively from the branches of the hepatic artery. This procedure is similar to intra-arterial infusion of chemotherapy. But in TACE, there is the additional step of blocking (embolizing) the small blood vessels with different types of compounds, such as gelfoam or even small metal coils. Thus, TACE has the advantages of exposing the tumor to high concentrations of chemotherapy and confining the agents locally since they are not carried away by the blood stream. At the same time, this technique deprives the tumor of its needed blood supply, which can result in the damage or death of the tumor cells.There is no established standard protocol for TACE.If the procedure is successful (>50% lipiodol uptake in necrotic tumor demonstrated on the postprocedural CT scan), the embolization is repeated in 6-8 weeks. If the lipiodol uptake is less than 50%, the authors repeat the CT scan in 6-8 weeks. If the size of the tumor is reduced, repeat TACE may be considered.The second TACE treatment should first be performed in previously untreated tumors.The third treatment completes a normal course, but further treatments are performed in patients with residual disease.


The type and frequency of complications of TACE and intra-arterial chemotherapy are similar. The potential disadvantage of TACE is that blocking the feeding vessels to the tumor(s) may make future attempts at intra-arterial infusions impossible. Moreover, so far, there are no head-to-head studies directly comparing the effectiveness of intra-arterial infusion versus chemoembolization. Studies in Japan have shown that TACE can downstage HCC. In other words, the tumors shrank enough to lower (improve) the stage of the cancer. From the practical point of view, shrinking the tumor creates the option for surgery in some of these patients. Otherwise, these patients had tumors that were not operable (eligible for operation) because of the initial large size of their tumors. More importantly, these same studies showed an improvement in survival in patients whose tumors became considerably smaller. In the U.S., trials are underway to see whether doing TACE before liver transplantation increases patient survival as compared to liver transplantation without TACE.

It is safe to say that TACE or intra-arterial chemoinfusion are palliative treatment options for HCC. However, they are not curative (Fewer than 50% of patients will have some shrinkage in tumor size. Further, they can be used only in patients with relatively preserved liver function. Several randomized trials have established this procedure as standard of care for hepatocellular cacrinoma and neuroendocrine carcinoma. 

Livraghi T .Guidelines for treatment of liver cancer. Eur J Ultrasound. 2001 Jun;13(2):167-76.

Blue Cross Blue Shield Association, Transcatheter Arterial Chemoembolization of Hepatic Tumors. TEC Assessment, March 2001; (15): 22.

 

EVIDENCE-BASED PRACTICE:
Calogero Cammà, Filippo Schepis, Ambrogio Orlando, Maddalena Albanese, Lillian Shahied, Franco Trevisani, Pietro Andreone, Antonio Craxì, and Mario Cottone
Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Meta-Analysis of Randomized Controlled Trials
Radiology, Jul 2002; 224: 47 - 54.

NCCN Drugs and Biologicals Compendium VI 2006