Chemotherapy For Hepatocellular Carcinoma Research Articles

Expression profile of hepatic drug transporters in patients with hepatocellular carcinoma

e22026 Background: Hepatocellular carcinoma (HCC) does not respond sufficiently to chemotherapy. It has been demonstrated that several transporters can cause drug resistance in tumor cells. In human liver, various drug transporters are expressed and play pivotal roles in hepatic uptake and excretion of drugs. In HCC, the expression profile of hepatic drug transporters may be altered due to pathophysiological changes. However, limited data are available on their expression and regulation in HCC tissues. The aims of this study were to determine the expression levels of hepatic drug transporters in HCC patients and to identify transporter specifically regulated in HCC tissues. Methods: The mRNA expression levels of 17 drug transporters, including 9 solute carrier (SLC) transporters (OAT2, OAT7, OATP1B1, OATP1B3, OATP2B1, OCT1, OCTN2, MATE1 and PEPT1) and 8 ATP-binding cassette (ABC) transporters (R1, MRP1–6 and BCRP), were determined by real-time RT-PCR in cancerous and non-cancerous liver tissues from 57 patients with HCC. Protein expression level was evaluated by Western blot analysis. In addition, DNA methylation status in promoter region of transporter gene was analyzed using bisulfite sequencing. Results: The mRNA expression levels of 11 transporters (OAT7, OCTN2, MATE1, PEPT1, R1, MRP1–6) were significantly increased (1.45 to 4.74-fold, p<0.05) in HCC tissues compared with non-cancerous liver tissues, whereas only OCT1 mRNA was significantly decreased (0.61-fold, p=0.0004). Notably, MRP4 mRNA showed the highest increase, which was consistent with the marked augmentation in the protein level. The frequency of methylation in MRP4 promoter region was comparable between HCC and non-cancerous liver tissues, suggesting other mechanisms than DNA methylation for MRP4 up-regulation. Interestingly, the mRNA expression levels of MRP4 did not change with the differentiation of HCC. Conclusions: It was revealed that most of the hepatic drug transporters were elevated in HCC tissues. Furthermore, we first identified that MRP4 showed remarkable increase in protein as well as mRNA expression levels. These findings suggest that MRP4 is a novel candidate for diagnostic marker and a target molecule to reverse multidrug resistance in chemotherapy for HCC. No significant financial relationships to disclose.

Hepatocellular carcinoma presenting with lung metastasis: Clinical characteristics and prognostic factors

e15604 Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) has been limited, but sorafenib has changed the strategy treating for metastatic HCC. The lung is one of the most common metastatic sites for HCC. Therefore, we focused on clinical features and prognostic factors of HCC patients (pts) with lung metastasis in this study. Methods: Between January 2000 and April 2008, 1,117 HCC pts were admitted into our division. During this period, extrahepatic metastasis was detected in 286 pts, and the initial metastatic site was lung in 130 pts. The relationships between the characteristics of these pts at the time of lung metastasis detection and prognosis were examined. Results: There were 107 males and 23 females. Median age was 64 years. The Child-Pugh classification was A in 84 pts, B in 32 pts. HCV Ab was positive in 57 pts, HBs Ag was positive in 46 pts, and both were negative in 27 pts. The median survival time of all pts was 298 days. Univariate analysis revealed 12 of the 20 variables evaluated to be significantly associated with survival time: number of lung metastasis, presence of intrahepatic HCC, maximum size of intrahepatic HCC, presence of tumor thrombus, AFP, PIVKA II, albumin, prothrombin time, ALP, presence of ascites, Child-Pugh classification, and previous history of hepatic resection. Multivariate analysis using the Cox proportional hazards model demonstrated a lower number (≤5) of lung metastases (p<0.0001), the absence of intrahepatic HCC (p=0.0002), and the absence of ascites (p=0.0339) to be independent favorable prognostic factors. Conclusions: These results may provide useful reference data for determining treatment strategies and planning further clinical trials involving HCC patients with lung metastasis. No significant financial relationships to disclose.

Palliative chemotherapy for patients with recurrent hepatocellular carcinoma after liver transplantation

The majority of patients with post-transplantation recurrence of hepatocellular carcinoma (HCC) have extrahepatic metastases and multifocal lesions. Therefore, they have few treatment options and may not be amenable for local therapy. The safety and efficacy of palliative chemotherapy in this population has not been reported. We retrospectively analyzed 24 patients who received palliative chemotherapy for recurrent HCC after liver transplantation between January 2000 and December 2006 at the Seoul National University Hospital. The mean age of patients was 55 years (range 42-70 years). The most commonly used chemotherapeutic regimens were 5-fluorouracil (5-FU)/cisplatin (n = 9), which was followed by capecitabine/cisplatin (n = 4), 5-FU/mitomycin (n = 3), 5-FU/oxaliplatin (n = 1), S-1 (n = 1), capecitabine (n = 1), gemcitabine/oxaliplatin (n = 1), gemcitabine/cisplatin (n = 1), 5-FU/interferon (n = 1) and sorafenib (n = 2). The Grade 3/4 hematological toxicity was neutropenia (29.1%), thrombocytopenia (20.9%) and anemia (20.9%). There were no cases of neutropenic fever or bleeding events. The Grade 3/4 non-hematological toxicity included elevation of liver transaminase (8.4%) and jaundice (16.7%). No patient showed an objective response and four patients (16.7%) demonstrated stable disease. The median time to progression was 7.0 weeks (95% CI 5.8-8.2) and the median overall survival was 16.6 weeks (95% CI 10.1-23.1). Palliative chemotherapy can be delivered to patients with recurrent HCC after liver transplantation with tolerable toxicity. However, the efficacy to date is not satisfactory. Therefore, more effective systemic chemotherapy is needed for this group of patients.

肝癌治療後3年を経過して発症したt(8;21)を伴う治療関連性AML (M2)

肝癌治療後3年を経過して発症したt(8;21)を伴う治療関連性AML (M2)

Preparation and Identification of Monoclonal Antibody Against Human Hepatocellular Carcinoma with a Novel Immunization

The purpose of this study was to prepare and identify a novel monoclonal antibody (MAb) against human primary hepatocellular carcinoma (PHC) with high specificity and activity. The hepatocellular carcinoma cell line HepG2 was used to immunize BALB/c mice for preparing MAb with the classic hybridoma production technique. Tail vein injection immunization combined with intrasplenic injection was applied for improvement. Immunoperoxidase staining studies showed that the MAb was reactive to HepG2 and another hepatocellular carcinoma cell line, SMMC7721, 98.5% (67/68) specimens of hepatocellular carcinoma, but not to normal human liver tissues and tissues derived from the other malignant tumors, except one of the five specimens of cholangiocarcinoma with dubious staining. Laser confocal scanning microscope (LCSM) analysis indicated that the MAb reacted with the whole cell, including the membrane fractions and the cytoplasm. The hybridoma cell contained 103 +/- 5 chromosomes, and the MAb was identified as IgM subclass by ELISA. It was concluded that this combined immunization can effectively produce highly specific MAb against PHC, and this MAb may be of potential use as a targeting agent for radionuclide therapy and chemotherapy for hepatocellular carcinoma.

New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy

There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial alpha-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point. Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival. Of 188 patients, 117 patients with elevated serum AFP (> 20 microg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival. Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.

Sorafenib in Hepatocellular Carcinoma: Separating the Hype From the Hope

Sorafenib in Hepatocellular Carcinoma: Separating the Hype From the Hope

Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor beta tyrosine kinases. Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients.

Interventional radiology in liver cancer

Surgery optimizes survival rates for liver cancer but is feasible in only a limited number of patients.Interventional techniques can increase the proportion of patients eligible for surgery.Radiofrequency ablation has been shown to give results not far short of surgery in patients who are unsuitable for surgery.Chemoembolization and selective internal radiation treatment have survival benefits over systemic chemotherapy in hepatocellular carcinoma and colorectal metastases, respectively. For many years, interventional radiology has played a role in the management of patients with malignant disease that affects the liver. In the past, this role was mainly related to palliative procedures. Over the last decade, we have witnessed the ascent of many percutaneous and endovascular therapeutic techniques that have defined the new specialty of interventional oncology. This article focuses on interventional radiology treatments for hepatocellular carcinoma and colorectal liver metastases. We review the standard te...

Synergistic Growth Inhibition by 9-cis-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells

A malfunction of retinoid X receptor-alpha (RXRalpha) due to phosphorylation by the Ras/mitogen-activated protein kinase signaling pathway is associated with the development of hepatocellular carcinoma (HCC). The humanized anti-HER2 monoclonal antibody trastuzumab inhibits the activation of HER2 and its multiple downstream signaling pathways, including the Ras/mitogen-activated protein kinase pathway. In this study, the effects of phosphorylation of RXRalpha on the ability of RXRalpha ligand 9-cis-retinoic acid (9cRA) and trastuzumab to inhibit growth of HCC cells was examined. The effects of a combination of 9cRA plus trastuzumab on the inhibition of cell growth in HLF human HCC cells which express constitutive activation of HER2 protein were examined. The combination of 9cRA plus trastuzumab synergistically inhibited the growth of HLF cells without affecting the growth of Hc normal human hepatocytes. Combined treatment with these agents acted synergistically to induce apoptosis in HLF cells. The treatment of HLF cells with trastuzumab alone inhibited the phosphorylation of HER2, RXRalpha, ERK, Akt, and Stat3 proteins and these effects were enhanced when the cells were cotreated with 9cRA. Reporter assays indicated that the combination of 9cRA plus trastuzumab markedly increased both the retinoic acid responsive element and retinoid X responsive element promoter activities in HLF cells. 9cRA and trastuzumab cooperatively inhibit the activation of HER2 and its downstream signaling pathways, subsequently inhibiting the phosphorylation of RXRalpha and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.

Clinical outcomes of systemic chemotherapy in hepatocellular carcinoma patients with multiple lung metastases

Advanced hepatocellular carcinoma (HCC) with multiple lung metastases has a poor prognosis with no effective treatment having been established. This study evaluated the outcomes of systemic chemotherapy for advanced HCC with multiple lung metastases. Between January 2000 and December 2006, 68 patients were diagnosed with HCC presenting with multiple lung metastases. Sixteen patients in the terminal stage, such as Child-Pugh grade ;C' or an Eastern Cooperative Oncology Group performance status exceeding grade 2, were excluded from the analysis. The following treatment modalities were applied: 26 patients received primary tumor treatment (transarterial chemoembolization or intra-arterial chemotherapy) with systemic chemotherapy, 10 patients received primary treatment only, 8 patients received systemic chemotherapy only, and 8 patients received highly supportive care. The treatment responses and median survival times for the modalities were analyzed and compared. The median age of the 52 analyzed patients (45 males) was 52.4 years. The most common etiology of HCC was chronic hepatitis B virus infection (n=44, 84.6%) followed by hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown in 6 cases (11.5%). The treatment modality had no significant effect on the treatment response rate (P=0.432) or median survival time (133, 66, 74, and 96 days for primary tumor treatment with systemic chemotherapy, primary tumor treatment only, systemic chemotherapy only, and highly supportive care, respectively; P=0.067). We found that systemic chemotherapy was not effective in treating HCC presenting with multiple lung metastases. Improving the effectiveness of systemic treatment and selecting patients who would benefit from such treatment remains a major challenge.

Interferon‐γ sensitizes hepatitis B virus‐expressing hepatocarcinoma cells to 5‐fluorouracil through inhibition of hepatitis B virus‐mediated nuclear factor‐κB activation

Nuclear factor (NF)-kappaB is important for immune responses and cell survival; however, abnormal activation of NF-kappaB is linked with many types of diseases, including hepatocellular carcinoma (HCC). Our previous report indicated that hepatitis B virus (HBV) induces NF-kappaB activation through NF-kappaB-inducing kinase (NIK), and this can be blocked specifically by interferon (IFN)-gamma. In the present study, we report that HBV expression in HCC cell lines induces drug resistance against 5-fluorouracil (5-FU). This drug resistance was abolished by inhibition of NF-kappaB activation through small interfering RNA-mediated NIK 'knockdown' and IFN-gamma treatment. In addition to the reduced NF-kappaB activation and drug resistance, the upregulated growth arrest- and DNA damage-inducible protein 45beta (Gadd45beta) in HBV-expressing HCC cell lines was downregulated by the small interfering RNA-mediated NIK knockdown and IFN-gamma treatment. The overexpression of Gadd45beta in HCC cell lines also induces drug resistance against 5-FU. Based on our data, we suggest that IFN-gamma treatment might be helpful for chemotherapy in HBV-integrated HCC through inhibition of the NIK-mediated NF-kappaB activation and downregulation of the NF-kappaB target gene Gadd45beta.

Radiation‐induced hepatic toxicity after radiotherapy combined with chemotherapy for hepatocellular carcinoma

The purpose of the present study was to analyze hepatic toxicity following radiotherapy combined with regional chemotherapy for hepatocellular carcinoma (HCC). From 2001 to 2003, a total of 132 patients with HCC received 3-D conformal radiation therapy (3D-CRT) combined with chemotherapy. Patients were divided into two groups based on drug localization: the transcatheter arterial chemoembolization (TACE) group, where the chemotherapeutic drug (adriamycin) was localized within the tumor, and the non-TACE group, where the drugs (adriamycin, cisplatin, 5-fluorouracil) were diffusely spread over the entire liver. Patients were evaluated by biochemical parameters for any hepatic toxicity prior to, during, and until 12 months after 3D-CRT. Hepatic toxicity was defined as radiation-induced liver disease (RILD) or combined modality-induced liver disease (CMILD), which is defined as RILD with abnormal elevation of total bilirubin levels. In the TACE group, three patients developed RILD (5.6%) and none developed CMILD. In the non-TACE group, three patients (3.7%) and seven patients (8.8%) developed RILD and CMILD, respectively. Hepatic toxicity following radiotherapy combined with regional chemotherapy for HCC might be influenced by the distribution of the chemotherapeutic drugs. A more precise understanding of hepatic toxicity from chemoradiotherapy will help design optimal treatments for HCC.

A phase II study of pegylated liposomial doxorubicin (PLD) and gemcitabine (G) in the treatment of hepatocellular carcinoma (HCC) not suitable for loco-regional therapy

4585 Background: There is no gold standard pharmacological treatment for HCC not suitable for loco-regional therapy. Antracyclines have been often used for the chemotherapy of HCC with low efficacy and well known toxicity. Availability of new drugs and in particular of PLD could enhance the chance of treatment and contain side-effects. Gemcitabine is active against the most solid tumors. Patients and Methods: We enrolled 35 patients (PTS) with histological diagnosis of HCC not suitable for loco-regional treatment and adequate haematological function.; median age was 63.2 (range 44.0–77.4); male/female=29/6; PS=0 in 30 PTS, PS=1 in 4 PTS and PS=2 in 1 PT. Eighteen PTS had metastatic disease. Prior treatments were TACE in13 PTS, PEI in 9, surgery in 12, RFTA in 5 and chemotherapy in 3. Nineteen patients had Child-Pough A-B cirrhosis HBV-HCV related. PLD was administered at the dose of 30mg/m2 over a 60’ infusion every 28 days and G at the dose of 1,000mg/m2 over 30’ infusion days 1 and 8 every 28 days. Instrumental response evaluation was performed every 3 cycles and treatment was continued until disease progression or major toxicity evidence. Results: All PTS were valuable for toxicity: G1–2 toxicity was neutropenia in 5 PTS, thrombocytopenia in 7, mucositis in 3 and PPE in 3. G3–4 toxicity was neutropenia in 6 PTS and thrombocytopenia in 1. Thirty-four PTS were valuable for response with CR in 2, PR in 6, SD in 12 and PD in 14. Thirty-four PTS were valuable for TTP: median was 6.2+ months (range 1.9–31.7+). All PTS were valuable for OS: median was 8.8+ months (range 1.9–36.5+). Conclusions: The combination of PLD and G is safe and effective in treatment of HCC. No life-threatening toxicity was experienced and disease control rate was about 60%. No significant financial relationships to disclose.

Clinical outcomes of ATP-tumor chemosensitivity assay directed chemotherapy in hepatocellular carcinoma

This study aims to investigate the clinical response of ATP tumor chemosensitivity assay (ATP-TCA) directed chemotherapy regimens delivered via hepatic artery infusion in 104 cases of primary liver carcinoma (PLC). Tumor tissue was obtained via laparotomy and cultivated in vitro. This tissue was put through the assay to determine chemosensitivity. A single drug regimen of either 5-FU, MMC and ADM and a combination drug regimen were used. The treatment assigned was dependent on the result of the ATP-TCA. In the control group, 30 cases of diagnosed PLC were given the conventional three-combination drug. The two groups were evaluated after three courses of chemotherapy. The results are as follows. The overall response rate of sensitivity test ranged from 36% to 44% in the single drug therapy groups and 81% in the combination drug group. The clinical overall response rate was 75% in the treatment group and 56% in control group. The treatment group had better results than the control group as survival period over six months was 80% and over one year 44%. In the control group, survival period over six months was 60% and 30% over one year. In short, ATP-TCA directed chemotherapy shows better results for terminal stages of PLC in that you can decrease the dose of drugs thereby reducing the side-effects with possible improvements in therapeutic effects.

Synergistic growth inhibition by acyclic retinoid and vitamin K2 in human hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. However, effective chemopreventive and chemotherapeutic agents for this cancer have not yet been developed. In clinical trials acyclic retinoid (ACR) and vitamin K(2) (VK(2)) decreased the recurrence rate of HCC. In the present study we examined the possible combined effects of ACR or another retinoid 9-cis retinoic acid (9cRA) plus VK(2) in the HuH7 human HCC cell line. We found that the combination of 1.0 microM ACR or 1.0 microM 9cRA plus 10 microM VK(2) synergistically inhibited the growth of HuH7 cells without affecting the growth of Hc normal human hepatocytes. The combined treatment with ACR plus VK(2) also acted synergistically to induce apoptosis in HuH7 cells. Treatment with VK(2) alone inhibited phosphorylation of the retinoid X receptor (RXR)alpha protein, which is regarded as a critical factor for liver carcinogenesis, through inhibition of Ras activation and extracellular signal-regulated kinase phosphorylation. Moreover, the inhibition of RXRalpha phosphorylation by VK(2) was enhanced when the cells were cotreated with ACR. The combination of retinoids plus VK(2) markedly increased both the retinoic acid receptor responsive element and retinoid X receptor responsive element promoter activities in HuH7 cells. Our results suggest that retinoids (especially ACR) and VK(2) cooperatively inhibit activation of the Ras/MAPK signaling pathway, subsequently inhibiting the phosphorylation of RXRalpha and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.

Pin1 Interacts With a Specific Serine-Proline Motif of Hepatitis B Virus X-Protein to Enhance Hepatocarcinogenesis

The peptidyl prolyl isomerase Pin1 frequently is overexpressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is the most common etiologic agent in HCC, and its encoded X-protein (HBx) is oncogenic and possesses a serine-proline motif that may bind Pin1. The role of Pin1 in hepatocarcinogenesis, particularly in HBV-related HCC, was investigated. Immunohistochemical staining was performed to evaluate the prevalence of Pin1 overexpression in HCCs of different etiologies. Glutathione S-transferase pull-down and co-immunoprecipitation experiments were used to validate the physical interaction between Pin1 and HBx. Reporter assay, cell proliferation assay, and xenotransplantation experiments were used to show the functional consequence and importance of Pin1-HBx interaction in hepatocarcinogenesis. We showed preferential Pin1 overexpression in HBV-related tumors and confirmed the interaction between Pin1 and HBx at the specific serine-proline motif. Pin1 overexpression increased the protein stability of HBx. Furthermore, HBx-mediated transactivation was enhanced by co-expression of Pin1. HepG2 expressing Pin1 and HBx showed a synergistic increase in cellular proliferation, as compared with cells expressing Pin1 or HBx alone. Furthermore, concomitant expression of Pin1 and HBx in the nontumorigenic human hepatocyte cell line MIHA led to a synergistic increase in tumor growth. Finally, in Hep3B cells with suppressed Pin1 expression, HBx-enhanced tumor growth in nude mice was abrogated. Pin1 binds HBx to enhance hepatocarcinogenesis in HBV-infected hepatocytes. The discovery of an interaction between Pin1 and HBx will further our understanding of the molecular pathogenic mechanism of HBV-related HCC in human beings.

2176: Radiation-Induced Hepatic Toxicity in Radiotherapy Combined With Chemotherapy for Hepatocellular Carcinoma

2176: Radiation-Induced Hepatic Toxicity in Radiotherapy Combined With Chemotherapy for Hepatocellular Carcinoma

Emerging drugs for hepatocellular carcinoma

Hepatocellular carcinoma is often diagnosed at an advanced stage, when potentially curative surgical or local ablative therapies are not feasible. There is no effective chemotherapy for hepatocellular carcinoma. Recent advances in cancer biology suggest that a limited number of signalling pathways may be responsible for uncontrolled cell proliferation, the major cellular alteration responsible for the cancer phenotype. Novel anticancer agents target these critical pathways, including the receptor tyrosine kinase pathways, the Wnt/β-catenin signalling pathway, the ubiquitin/proteasome degradation pathway, the DNA methylation and histone deacetylation pathways, the PI3 kinase/AKT/mTOR pathway, angiogenic pathways, telomerase and the cell cycle. These agents hold promise for improving the outcome of patients with intermediate and advanced hepatocellular carcinoma. Because of the high prevalence of liver cirrhosis in hepatocellular carcinoma patients, to achieve long-term survival of the majority of patients, targeted anticancer therapies will need to be coupled with strategies aimed at reversing the progression of chronic liver disease.

A phase I-II study of liposomal doxorubicin (LD) in the treatment of hepatocellular carcinoma (HCC) not suitable for loco-regional therapy

4227 Background: There is no gold standard pharmacological treatment for HCC not suitable for loco-regional therapy. Antracyclines have been often used for the chemotherapy of HCC with low efficacy...