Hepatocellular Carcinoma: Targeted Therapy and Multidisciplinary P32

18 Transarterial Chemoembolization 295 Future Directions/Conclusions The excitement generated by the release of the SHARP trial results (systemic chemotherapy with Sorafenib) overshadowed reality. That is, the survival benefit seen by Child-Pugh A patients with unresectable HCC treated with Sorafenib was a modest 2.8 months. The initial enthusiasm, more than anything else, highlights the historical absence of measurable progress in the treatment of HCC among the medical oncology community. Therefore, and despite these modest advances in the treatment of HCC, TACE will likely remain the most important treatment option. That is not to say that TACE is an optimal treatment or that these advances have not shaped future clinical trials. While TACE occasionally results in complete and sustained tumor response, in the majority of patients there is eventual regrowth of the neoplasm, underlying TACE’s inability to completely eradicate the disease or to permanently sustain its initial good response. Currently, many combination treat-ments are planned that aim to attack HCC’s critical survival points. For example, a TACE-Avastin as well as a TACE-Sorafenib trial is underway, which aims to pre-vent HCC regrowth after TACE by inhibiting tumor angiogenesis. TACE technique is also evolving, in current trials. Porous particles loaded with chemotherapeutics (i.e., doxorubicin eluting beads – DEBs) are replacing simple drug-ethiodol infu-sions. Such particles further increase the residence time of chemotherapy within the tumor and have prolonged drug eluting characteristics, properties that fur-ther enhance tumoricidal effect and reduce systemic toxicities (Fig. 18.8). What-ever the new standard of care treatment is for unresectable HCC, transarterial chemoembolization is evolving and will undoubtedly remain one of the most important – if not the most important – component. Fig. 18.8 Relative plasma doxorubicin concentrations. Intra-arterial infusion (solid line) via the hepatic artery shows the least optimum pharmacokinetic profile with an early spike in plasma concentration and the highest area-under-curve value. TACE with lipiodol (dashed line) decreases both the peak average plasma concentration of doxorubicin and the area-under-curve. Treatment with doxorubicin eluting beads (single value, peal plasma concentration) further decreases the peak plasma concentration of doxorubicin. Data are normalized to peak plasma concentration of doxorubicin after intra-arterial infusion 296 C. Georgiades and J.-F. Geschwind In conclusion, TACE has been shown to provide the longest survival benefit among all treatment options for unresectable HCC. Combination therapies that include TACE, ablation, and maintenance chemotherapy with newer, targeted agents are becoming the standard of care for such patients. Many challenges will be encountered in the future for HCC treatment. For example, what is the best com-bination treatment protocol and which chemotherapy should we use? Locoregional treatments and then follow-up with systemic chemotherapy or the reverse? What to do we need to use with those patients who respond to these new treatments? If they are downstaged into criteria for resection or transplantation, will it be beneficial? If a significant percent of patients is indeed downstaged to transplantation criteria, what will be the impact on liver availability? References 1. Devita VT, Lawrence TS, Rosenberg SA, eds (2008) DeVita, Hellman & Rosenberg’s Cancer: principles and practice of oncology, 8th ed. Wolters Kluwer and Lippincot Williams & Wilkins, Philadelphia, PA 2. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Raoul J, Zeuzem S, Poulin-Costello M, Moscovici M, Voliotis D, Bruix J, For the SHARP Investigators Study Group J Clin Oncol (2007) Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). ASCO Annual Meeting Proceedings Part I 25(June 20 Supplement), LBA1 3. Llovet JM, Real MI, Montana X et al (2002) Arterial embolization or chemoemboliza-tion versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 1:1734–1739 4. Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unre-sectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 1:47–54 5. Lo CM, Ngan H, Tso WK et al (2002) Randomized control trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 1:1164–1171 6. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocel-lular carcinoma: chemoembolization improves survival. Hepatology 1:429–442 7. Yamagiwa K, Shiraki K, Yamakado K et al (2008) Survival rates according to the Cancer of the Liver Italian Program scores of 345 hepatocellular carcinoma patients after multimodal-ity treatments during a 10-year period in a retrospective study. J Gastroenterol Hepatol 1: 482–490 8. Yamakado K, Nakatsuka A, Takaki H et al (2008) Early stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy. Radiology 1:260–266 9. Graziadei IW, Sandmueller H, Waldenberger P et al (2003) Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transplant 1:557–563 10. Stockland HA, Walser EM, Paz-Fumagalli R, McKinney JM, May GR (2007) Preoperative chemoembolization in patients with hepatocellular carcinoma undergoing liver transplan-tation: influence of emergent versus elective procedures on patient survival and tumor recurrence rates. Cardiovasc Intervent Radiol 1:888–893 11. Ravaioli M, Grazi GL, Ercolani G et al (2004) Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation. Transplantation 1:1780–1786 18 Transarterial Chemoembolization 297 12. Buijs M, Vossen JA, Frangakis C, Hong K, Georgiades CS, Chen Y, Liapi E, Geschwind JF (2008) Nonresectable hepatocellular carcinoma: long-term to treated with transarterial chemoembolization: a single centre experience. Radiology 1:346–354 13. Poon RT, Tso WK, Pang RW et al (2007) A phase I/II trial of chemoembolization for hepato-cellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 5:1100–1108 Chapter 19 Chemoembolization with Drug-Eluting Beads Robert C.G. Martin and Stewart Carter Keywords Liver-directed therapy · Chemoembolization · Drug-eluting bead · Doxorubicin · Hepatocellular Introduction Primary hepatic carcinoma remains a relatively uncommon disease in North America and Western Europe (0.5–2.0% of all cancers) [1, 2]. However it remains a much larger fraction (20–40%) in developing countries and is the 5th–6th most common malignancy worldwide (approximately 5.6% of all cancers) [3, 4]. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver (70–85%) with an estimated 500 thousand to 1 million new cases annually and an associated mortality of approximately 600,000 [3, 5]. Recent studies in the USA have shown that the incidence of HCC is increasing, most likely related to chronic HCV infection [6]. Unfortunately, many of these patients will have diffuse, multifocal disease ren-dering them unresectable, defined as the inability to remove or ablate all tumors and leave enough normal liver parenchyma to regain an acceptable quality of life. Additionally, many patients have significant comorbid conditions that preclude a major liver resection. Not long ago, most patients with unresectable liver can-cers had few therapeutic options other than systemic chemotherapy. The last two decades have seen the development of several hepatic-directed treatment options that are expanding the therapeutic armamentarium of the clinician and lengthening the patient’s survival. It is for this very reason that other treatment modalities are being investigated for their roles in enhancing the results in the treatment of early, intermediate, R.C.G. Martin ( ) Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA K.M. McMasters, J.-N. Vauthey (eds.), Hepatocellular Carcinoma, 299 DOI 10.1007/978-1-60327-522-4_19, C Springer Science+Business Media, LLC 2011 ... - tailieumienphi.vn