aclarubicin and Liver-Neoplasms

A female patient in whom acute nonlymphocytic leukemia (ANLL, FAB-M6) developed during treatment of hepatocellular carcinoma (HCC) is described. Two years after partial hepatectomy and subsequent chemotherapy, leukemia developed following a 2 month preleukemic stage. Chromosomal analysis revealed an abnormal karyotype, 46,XX,-5, + der(5)t(3;5)(q25;q31). The balanced translocation t(3;5) has been observed in all types of ANLL and MDS except for ANLL M3 subtype. We summarize patients with ANLL M6 and t(3;5).

Topics: Aclarubicin; Adolescent; Adult; Aged; Anemia, Refractory, with Excess of Blasts; Carcinoma, Hepatocellular; Child; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 5; Cytarabine; Daunorubicin; Doxorubicin; Female; Hepatectomy; Hepatitis B; Humans; Leukemia, Erythroblastic, Acute; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Prednisolone; Remission Induction; Translocation, Genetic

Fifty-five patients with hepatic metastasis from colorectal cancer underwent curative hepatic resection. Postoperative intraportal infusion of 5-fluorouracil (500mg per day) for 14 days from 21 postoperative days (POD) and lipiodol-aclarubicin (40mg) at 35 POD was carried out in twenty-eight patients for reducing the recurrence in the remnant liver and improving the prognosis. Twenty-seven patients had hepatectomy alone as controls. Intraportal infusion chemotherapy did not induce any hepatotoxicity and hematologic severe abnormalities. The cumulative survival rates for the infusion group and the control group, respectively, were 89.3% and 63.0% at 1 year; 55.2% and 43.3% at 2 year; 27.0% and 27.5% at 3 year. The survival rate for the infusion group was significantly higher than that for the control group at 1 year (p < 0.05). No difference of the recurrent rate in the remnant liver was found between the two groups. It is suggested that intraportal infusion chemotherapy after curative hepatic resection for colorectal liver metastasis might improve survival rate at the early postoperative period. Intraportal infusion chemotherapy could be an effective adjuvant therapy especially in the patients with bilateral and multiple hepatic metastasis.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Hepatectomy; Humans; Infusions, Intravenous; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Portal Vein; Prognosis; Survival Rate

In targeted chemotherapy, Lipiodol Ultrafluid was used as a carrier of anticancer drugs; these combinations were termed oily anticancer agents. Arterial injection therapy with these oily anticancer agents was performed in 330 patients with unresectable hepatocellular carcinoma (HCC) and 110 patients with unresectable metastatic liver cancer. The alpha-fetoprotein (AFP) level decreased in 178 of 186 AFP-positive patients with HCC. Tumor size was reduced in 256 of 269 evaluable patients with HCC. The treatment seemed to prolong survival and in 193 HCC patients who were good candidates for therapy (those without Child C liver cirrhosis, without tumor occupying all four segments of the liver, or without extrahepatic spread) the 1-, 2-, and 5-year survival rates were 85, 52, and 34% respectively. In the 110 patients with metastatic liver cancer, the carcinoembryonic antigen level and tumor size were reduced. The 1-, 2-, and 5-year survival rates of these 110 patients were 61, 32, and 22% respectively.

Topics: Aclarubicin; Adolescent; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antineoplastic Agents; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Doxorubicin; Drug Delivery Systems; Female; Humans; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Mitomycin; Polystyrenes; Survival Analysis; Survival Rate; Treatment Outcome; Zinostatin

In May 2006, a 72-year-old man with acute myelogenous leukemia (M4Eo) was admitted to our hospital. He had been receiving antiandrogen treatment for prostate cancer (after an operation in 1998) and treatment for diabetes mellitus. He received chemotherapy according to the JALSG GML200 protocol, which led to complete remission; however, in January 2007, his leukemia recurred. CAG combination chemotherapy also resulted in complete remission by May 2007. In August 2007, he developed multiple liver tumors, abdominal pain, and fever. Contrast-enhanced computed tomography revealed hypovascular tumors in both early and delayed phases. Angiography showed ring-like tumor staining and a massive tumor, similar to those seen in metastatic hepatocellular carcinomas (HCCs). He eventually died because of aggressive enlargement of liver tumors during the following month accompanied by the simultaneous recurrence of leukemia and unsuccessful embolization of the hepatic artery. Autopsy specimens showed fibrosis and considerable iron deposition in the liver, suggested secondary hemochromatosis due to transfusion. We also detected multiple moderately differentiated primary HCCs. Secondary hemochromatosis, androgen imbalance, and humoral factors from leukemic cells were believed to be the causes of the rapid onset and development of HCCs.

Topics: Aclarubicin; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cytarabine; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Hemochromatosis; Humans; Leukemia, Myeloid, Acute; Liver Neoplasms; Male; Neoplasms, Second Primary; Prostatic Neoplasms; Time Factors

To investigate the possibility of recombinant high-density lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.. Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.. The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26+/-5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 microg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 microg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs 3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 microg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 microg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells.. rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Cell Line, Tumor; Drug Carriers; Hepatocytes; Humans; Lipoproteins, HDL; Liver Neoplasms

To establish a novel formulation tumor-targeted drug carrier of lipophilic antitumor antibiotics, aclacinomycin A (ACM), folate-linked microemulsions were prepared and investigated both in vitro and in vivo.. Three kinds of folate-linked microemulsions with different polyethylene glycol (PEG) chain lengths loading ACM were formulated with 0.24 mol% folate-PEG(2000)-distearoylphosphatidylethanolamine (DSPE), folate-PEG(5000)-DSPE, and folate-lipid (without PEG linker) in microemulsions. In vitro studies were done in a human nasopharyngeal cell line, KB, which overexpresses the folate receptor (FR), and a human hepatoblastoma cell line, [FR(-)] HepG2. In vivo experiments were done in a KB xenograft by systemic administration of folate-linked microemulsions loading ACM.. The association of folate-linked microemulsions to KB cells could be blocked by 2 mmol/L free folic acid. Selective FR-mediated cytotoxicity of folate-linked microemulsions loading ACM was obtained in KB but not in HepG2 cells. The association of the folate-PEG(5000)-linked microemulsion and folate-PEG(2000)-linked microemulsion with the cells was 200- and 4-fold higher, whereas their cytotoxicity was 90- and 3.5-fold higher than those of nonfolate microemulsion, respectively. The folate-PEG(5000)-linked microemulsions showed 2.6-fold higher accumulation in solid tumors 24 hours after i.v. injection and greater tumor growth inhibition than free ACM.. These findings suggest that a folate-linked microemulsion is feasible for tumor-targeted ACM delivery. This study shows that folate modification with a sufficiently long PEG chain on emulsions is an effective way of targeting emulsion to tumor cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma; Chemistry, Pharmaceutical; Emulsions; Folic Acid; Hepatoblastoma; Humans; Lipids; Liver Neoplasms; Nanostructures; Nasopharyngeal Neoplasms; Phosphatidylethanolamines; Polyethylene Glycols; Tumor Cells, Cultured

A 46-year-old woman had undergone a mastectomy in 1994, and metastases to the lung, bones and liver were detected in 1998. Brain metastases were detected later. Chemotherapy consisting of docetaxel, aclarubicin and UFT was administered, and image diagnosis revealed that CR was achieved. The chemotherapy was continued on a long-term basis, both as an inpatient and outpatient. The total administered doses have reached 2,000 mg of docetaxel and 1,000 mg of aclarubicin. The CR is being maintained as of this writing, 2 years and 4 months after the detection of the metastases. The patient's course continues to be monitored.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Paclitaxel; Taxoids; Tegafur; Uracil

This study explored the possibility of achieving a better survival rate and reduced recurrence in the remaining liver in patients with colorectal hepatic metastases undergoing hepatic resection. Adjuvant postoperative regional chemotherapy was administered via the hepatic artery or the portal vein.. A retrospective study was performed on 174 patients after hepatic resection for colorectal metastases. These comprised 78 patients who had hepatic artery infusion (HAI) chemotherapy (HAI group), 30 who had portal vein infusion (PVI) chemotherapy (PVI group) and 66 who had no regional chemotherapy (resection alone group). The three groups were compared with one another in terms of complications, survival rate and patterns of recurrence.. Severe complications did not occur at any point during adjuvant HAI or PVI chemotherapy. The 5-year disease-free survival rate of patients in the HAI, PVI and resection alone groups were 35, 13 and 9 per cent respectively, including six hospital deaths. Patients in the HAI group showed significantly improved recurrence rates in the remaining liver compared with the resection alone group (P = 0.03), and more prolonged disease-free and overall survival than those in the PVI (P = 0.01 and P = 0.02 respectively) and resection alone (P = 0.0001 and P = 0.0006 respectively) groups.. This study suggests that adjuvant HAI chemotherapy after hepatic resection may have therapeutic potential for improved management of patients with colorectal metastases.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Hepatectomy; Humans; Infusion Pumps; Infusions, Intra-Arterial; Infusions, Intravenous; Injections; Lipids; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Survival Analysis

Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein.. Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment.. Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.

Topics: Aclarubicin; Aged; Antibiotics, Antineoplastic; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Gelatin Sponge, Absorbable; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplastic Cells, Circulating; Radiography

Topics: Aclarubicin; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Hepatocellular; Cyclosporins; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Multiple; Epirubicin; Humans; Liver Neoplasms; Tumor Cells, Cultured

Drug resistance is a major obstacle to successful chemotherapy of primary liver cancer, which is associated with high expression of the multidrug resistance (MDR) gene product P-glycoprotein (Pgp), a multidrug efflux transporter. The most effective single agents in treatment of primary liver carcinoma belong to the anthracycline family, yet several anthracyclines are known to be substrates for Pgp. In the present study, we compared four anthracyclines with respect to cell growth inhibition, intracellular accumulation and cellular efflux using the HB8065/R human hepatoma cell line which is rich in Pgp, and the Pgp-poor parental line HB8065/S. The anthracyclines were also administered in conjunction with the Pgp-modifying agents verapamil and SDZ PSC 833 to assess modulation of resistance. The HB8065/R cells were sensitive to aclarubicin (ACL) and highly resistant to epirubicin (EPI), doxorubicin (DOX) and daunorubicin (DNR). SDZ PSC 833 enhanced accumulation, decreased efflux and increased cytotoxicity of EPI, DOX and DNR in the HB8065/R cells, but none of these effects was seen with ACL. In conclusion, ACL is apparently not transported by Pgp and retains its activity in a multidrug-resistant human hepatoma cell line; such properties can be exploited for clinical purposes.

Topics: Aclarubicin; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Hepatocellular; Cell Division; Cell Membrane; Daunorubicin; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Epirubicin; Humans; Liver Neoplasms; Microscopy, Confocal; Tumor Cells, Cultured

This paper reports the results of experiments on the antihepatoma effects of live targeted drug delivery system--lyophilized aclacinomycin A polyisobutylcyanoacrylate nanoparticle (ACM-IBC-NP) in vitro and in vivo. The median inhibition concentration were found to be 0.28 micrograms.ml-1 and 0.34 micrograms.ml-1 of lyophilized ACM-IBC-NP and ACM respectively in vitro. The inhibition ratio of colony formation were found to be 99% and 88% of lyophilized ACM-IBC-NP and ACM respectively in vitro. The antihepatoma activity was shown to be significantly concentration dependent. The results showed that lyophilized ACM-IBC-NP and ACM possess strong cytotoxicity on human hepatoma cell 7703, and the cytotoxicity was not significantly different between lyophilized ACM-IBC-NP and ACM in vitro. The model of orthotopic transplantation of human hepatoma in nude mice were used for evaluation of the activity of lyophilized ACM-IBC-NP against hepatoma. The tumor inhibition rate were found to be 86.84% for lyophilized ACM-IBC-NP and 46.69% for ACM. The cell proliferative activity of hepatoma were found to be 20.83% by lyophilized ACM-IBC-NP and 72.50% by ACM. All the results indicate that lyophilized ACM-IBC-NP and ACM have clinical application potential and the antihepatoma activity of lyophilized ACM-IBC-NP was obviously higher than that of ACM.

Topics: Aclarubicin; Animals; Cyanoacrylates; Drug Delivery Systems; Enbucrilate; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Microspheres; Neoplasm Transplantation; Polymers; Proliferating Cell Nuclear Antigen; Tumor Cells, Cultured

A 59-year-old woman developed multiple hepatic tumors 20 years after resection of pheochromocytoma of the left adrenal gland. Thin-needle aspiration biopsy of the tumor at segment 2 of the liver under ultrasound control showed histology compatible to pheochromocytoma. Then, on the basis of the diagnosis of hepatic metastasis of malignant pheochromocytoma, transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastasis. After TAE, the size of the hepatic metastatic lesions was decreased. The present case suggests the necessity of long-term follow-up in pheochromocytoma cases.

Topics: Aclarubicin; Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Catecholamines; Chemoembolization, Therapeutic; Female; Hepatic Artery; Humans; Liver Neoplasms; Middle Aged; Mitomycin; Pheochromocytoma; Time Factors

In an attempt to investigate the interaction between the changes of cytokines and acute phase reactants after transcatheter arterial chemoembolization therapy (TACE), the levels of interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI) in the blood of patients with unresectable hepatocellular carcinoma (HCC) were measured. Before the therapy, serum IL-6 and plasma IL-8 levels were detectable in 77.8% and 28.5%, respectively, of patients with HCC. Levels of serum IL-6 and plasma IL-8 increased after TACE and reached a peak on day 3 in all patients (18/18) and in 87.5% of patients (12/14), respectively. Both blood levels of IL-6 and IL-8 reached a peak earlier than those of CRP and PSTI did after the therapy. When the maximal values of IL-6 were compared with those of CRP and PSTI, there were significant positive correlations (r = 0.63, P < 0.01 and r = 0.81, P < 0.01, respectively). Similarly, comparisons of the maximal values of IL-8 with those of CRP and PSTI gave a significant correlation (r = 0.68, P < 0.01 and r = 0.67, P < 0.05, respectively). However, no significant correlation was found between the elevation of IL-6 and IL-8.

Topics: Aclarubicin; Acute-Phase Reaction; C-Reactive Protein; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Cytokines; Humans; Interleukin-6; Interleukin-8; Liver Neoplasms; Trypsin Inhibitor, Kazal Pancreatic

Sixty-six consecutive patients with unresectable hepatocellular carcinoma (HCC) were treated with transcatheter arterial chemoembolization (TACE) using aclarubicin microspheres (ACRms) in combination with cisplatin suspended in iodized oil (Lipiodol, Laboratoire Guerbert, Paris, France) (CSL). The stages of the disease were as follows: Stage I (n = 1), Stage II (n = 10), Stage III (n = 26), and Stage IV (n = 29). The effectiveness of TACE was assessed by comparing ACRms with CSL with ACRms without CSL. Of 66 patients treated with ACRms and CSL, 62 (93.9%) could be examined for response. According to response criteria, there were 31 (50.0%) partial responses and 17 (27.4%) minor responses. In 13 cases (21.0%) there was no change and in 1 case (1.6%) there was progressive disease. The cumulative survival rate was 80.7% at 1 year, 64.2% at 2 years, and 50.6% at 3 years. The rates were significantly higher than those of the group treated with ACRms. Eleven patients in the ACRms and CSL group experienced clinical complications: cholecystitis (4.5%), pancreatitis (3.0%), liver abscess (3.0%), hepatic failure (3.0%), gastrointestinal bleeding (1.5%), and renal failure (1.5%). No lethal side effects related to the therapy were observed. TACE using ACRms in combination with CSL prolongs the survival of patients with unresectable HCC.

Topics: Aclarubicin; Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Female; Humans; Iodized Oil; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Staging; Survival Analysis; Treatment Outcome

Transcatheter arterial chemoembolization therapy using polylactic acid microspheres containing aclarubicin hydrochloride (ACR) was performed in 62 patients with primary hepatocellular carcinoma. These microspheres were about 200 microns in diameter and contained 10% (w/w) aclarubicin. A single dose of polylactic acid microspheres containing ACR (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 doses (a total of 160 treatments) in 62 patients. Antitumor effects were observed from the decrease in serum alpha-fetoprotein levels (82.1% of the patients) and in two dimensional size of tumor on computed tomography (93.6%). The cumulative survival rate was 54.3% at 1 year, 24.6% at 2 years, and 19.2% at 3 years, respectively, among 59 patients with unresectable tumors. In 3 resected liver specimens, there was a significant accumulation of ACR in the tumor, and severe necroses of the tumors were observed histologically. Systemic toxicity was mild and all patients tolerated this treatment. These results suggest that transcatheter arterial chemoembolization with the use of polylactic acid microspheres containing ACR is a useful tumor-targeting chemotherapy and is effective in the treatment of hepatocellular carcinoma.

Topics: Aclarubicin; Adult; Aged; alpha-Fetoproteins; Animals; Carcinoma, Hepatocellular; Dogs; Embolization, Therapeutic; Female; Humans; Infusions, Intra-Arterial; Lactates; Lactic Acid; Liver Neoplasms; Male; Microspheres; Middle Aged; Polyesters; Polymers

A new immunotherapy for hepatocellular carcinoma (HCC) using Freund's adjuvant and recombinant interleukin-2 (IL-2) combined with conventional transarterial chemoembolization therapy was performed. In 16 patients with HCC and one patient with metastatic liver cancer receiving this therapy, decrease and suppression of reelevation of alpha-fetoprotein after therapy was observed. Disappearance of tumor thrombi of HCC in the main portal vein was observed in a patient, and decrease of carcinoembryonic antigen was also observed in a patient with metastatic liver cancer. The present therapy using Freund's adjuvant and IL-2 is likely to open a new avenue for the treatment of patients with advanced liver cancer.

Topics: Aclarubicin; Adult; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Embolization, Therapeutic; Female; Freund's Adjuvant; Humans; Interleukin-2; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Recombinant Proteins

Chemosensitivity to six different types of antitumor drugs was assayed using the succinate dehydrogenase inhibition (SDI) test, with regard to effects of 29 tissues from primary hepatocellular carcinomas (PHC) and 12 metastatic liver cancers. Succinate dehydrogenase activity in the PHC was significantly decreased by adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR) (P less than 0.01), and 5-fluorouracil (5-FU), cisplatin (DDP) and carboquone (CQ) (P less than 0.05), as compared to findings in tissues from the metastatic liver tumors. In PHC, chemosensitivity to antitumor drugs in the SDI test was positive in 58.6% of tissues exposed to ADM, 60.7% with MMC, 11.1% with 5-FU, 65.4% with DDP, 65.5% with ACR and 64.3% with CQ. On the contrary, the positive rates seen in metastatic liver tissues were 18.2% in DDP and 8.3% in CQ, and there was no positive chemosensitivity in tissues exposed to ADM, MMC, 5-FU and ACR. Therefore, PHC will show a better response than metastatic liver cancers to antitumor drugs. Our observations show that the selection of sensitive drugs is most important to improve the response rate and the survival time of patients. The SDI test proves useful for planning clinical management.

Topics: Aclarubicin; Antineoplastic Agents; Carbazilquinone; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Drug Screening Assays, Antitumor; Female; Fluorouracil; Humans; Liver Neoplasms; Male; Mitomycin; Mitomycins; Succinate Dehydrogenase

The lipid lymphographic agent, Lipiodol ultrafluid has been found to remain selectively in hepatocellular carcinoma. Using this characteristic nature of Lipiodol, a new targeting anticancer chemotherapy was devised. In order to achieve targeting anticancer chemotherapy and useful anticancer effects, anticancer drugs must be dissolved or suspended in Lipiodol and diffuse out from the Lipiodol gradually. Oily anticancer agents such as SMANCS dissolved in Lipiodol (SMANCS/Lipiodol), Mitomycin C in Lipiodol (MMC/Lipiodol), Aclarubicin in Lipiodol (ACR/Lipiodol) and a mixture of these were administered by catheterizing the celiac or hepatic artery under X-ray monitoring in 216 patients with hepatocellular carcinoma. Remarkable anticancer effects of this targeting chemotherapy were achieved, the serum AFP level and tumor size both showing a decrease in 91% of cases. The survival period of patients with unresectable hepatoma treated with the present protocol was definitely longer than the comparison group.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Maleic Anhydrides; Mitomycin; Mitomycins; Naphthacenes; Polystyrenes; Zinostatin

Transcatheter hepatic arterial embolization therapy (TAE) is an established method for the treatment of hepatocellular carcinoma (HCC). We have developed a new embolus consisting of microspheres with a mean diameter of about 200 microns which are composed of biodegradable polymolecular polylactic and the anti-cancer agent, aclarubicin -HCl, in a ratio of 12% w/w. These microspheres were applied to 28 patients with inoperable HCC using the following method microspheres containing 50 mg of aclarubicin-HCl were injected through a catheter placed in the hepatic artery or one of its branches, 2 or 3 times at intervals of 2 to 4 weeks. The effectiveness was confirmed by decreased levels of serum AFP and regression of the tumor size, and the accumulated survival rate for 6 months was 83.3%.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Catheterization; Embolization, Therapeutic; Hepatic Artery; Humans; Lactates; Lactic Acid; Liver Neoplasms; Microspheres; Naphthacenes; Polyesters; Polymers