Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1976 to 1983, 28 patients (24 male and four female) with unresectable hepatocellular carcinoma (HCC) were treated by intraarterial chemotherapy at the Istituto Nazionale Tumori of Milan, Milan, Italy. Tumors were retrospectively classified by a previously proposed staging system. Two patients were classified as Stage I and 26 as Stage II. Liver cirrhosis was present only in the males (in 50% of them). Nineteen patients were treated with doxorubicin (Adriamycin [Adria Laboratories, Columbus, OH]) and nine with 5-fluorouracil. Systemic toxicity was mild, but the treatment induced hepatic toxicity (ascites, clinical jaundice, or biochemical impairment) in 18% of noncirrhotic and 66% of cirrhotic patients. Clinical reduction of hepatomegaly was observed in 50% of noncirrhotic versus 16% of cirrhotic patients. Doxorubicin was effective in 66% of noncirrhotic patients and 20% of cirrhotic patients, with an overall response rate of 42%. 5-fluorouracil was effective only in patients without cirrhosis, with an overall response rate of 22%. Overall median actuarial survival was 3.5 months, with a significant difference between noncirrhotic and cirrhotic patients (6 versus 2 months, respectively). Overall median survival of patients who responded to the treatment was 13 versus 2 months for nonresponders (P less than 0.001). Liver cirrhosis was the most important prognostic factor in terms of liver toxicity, response rate, and survival. This study emphasized the negative impact of the treatment on cirrhotic patients. Also, the real value of intraarterial administration of doxorubicin was investigated.
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PMID:Intrahepatic chemotherapy for unresectable hepatocellular carcinoma. 283 36

Chemoembolization therapy with arterial injection of a mixture of various anticancer agents (CDDP, ADR, MMC) and Lipiodol along with gelfoam particles was carried out on 158 cases of hepatocellular carcinoma between January 1985 and July 1987. In two groups using CDDP the tumor regressed 50% or more in higher percentage than in the groups without CDDP. The antitumor effect was more significant in the group using CDDP and ADR than in the group using CDDP alone. No significant side effect was noted in any case.
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PMID:[Chemoembolization therapy of hepatocellular carcinoma-antitumor effect and side effect]. 284 58

Twenty evaluable patients with primary or secondary neoplastic liver involvement received FUDR (0.2 to 0.3 mg/kg per day) by continuous infusion to the hepatic artery for 14 days, every 4 weeks, through a surgically implanted Infusaid (USA) pump. In addition to FUDR, MMC (15 mg/m2 every 6 to 8 weeks) was given to 14 patients with colorectal cancer and one patient with breast cancer, and ADR, (40 mg/m2 every 4 to 6 weeks) was given to 5 patients with hepatocellular carcinoma. MMC and ADR were given as a bolus injection, through the pump sideport. Radiation therapy to the liver (2,000 rads in fractions of 180 to 200 rads each) was given to eight patients with colorectal carcinoma. In total, the 20 patients received 218 months of treatment and 580 injections. The overall remission rate (complete, partial and minor response) was 55%; one patient with a colorectal carcinoma achieved a CR and seven patients (35%) a PR; three patients (15%) had a MR, and in eight patients (40%) stabilization of disease was observed. Overall median survival was 12 months: 15.5 months for colorectal cancer patients and 7.5 months for patients with hepatocellular carcinoma. Toxicity consisted mainly of chemical hepatitis, mild to severe peptic disease and sclerosing cholangitis. Hematological toxicity was not observed. These data suggest that chemotherapy through the hepatic artery, while still experimental, may be considered for selected patients with tumor confined to the liver.
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PMID:Treatment of primary and metastatic liver cancer using an implantable chemoinfusion pump. 284 96

Doxorubicin provides the most consistent response rate in hepatocellular carcinoma. We therefore initiated a trial with its analog 4'epidoxorubicin. Eighteen patients, all without prior treatment, were given the drug as a single agent every 3 weeks with dose escalation whenever possible. Five patients were treated by six-hour infusion and 13 by intravenous (IV) bolus injection, with the median dose being 90 mg/m2. The patients were of diverse ethnic background and included some with underlying cirrhosis and hepatitis B surface antigenemia. Three patients had partial remissions (6, 12, 48 weeks) for a response rate of 17%. Four patients also had prolonged stable disease (14, 26, 27, 38 weeks). Toxicity was mild, although cardiac toxicity developed in three patients at 685, 825, and 1,460 mg/m2 cumulative dose. The response to 4'epidoxorubicin in this study appears to be equivalent to the reported response rates for doxorubicin, with decreased toxicity.
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PMID:4'Epidoxorubicin (epirubicin): activity in hepatocellular carcinoma. 299 8

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.
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PMID:Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. 332 53

Chemosensitivity of liver cell carcinoma was studied by subrenal capsule assay. The method of assay was based on Bogden's one, but the antitumor activity was evaluated by tumor growth inhibition rate (TG-IR). The anticancer agent with more than 50% TG-IR was judged as positive in the chemosensitivity test. Of 3 human hepatoma cell lines transplanted in the subcutaneous space of nude mice, all of 3 were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 66.7%, 100%, 66.7%, 100% and 0%, respectively. Of 24 patients who provided fresh tumor specimens for the assay, 12 (50%) were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 25%, 16.7%, 16.7%, 33.3% and 8.3%, respectively. Our study suggested that 5-FU, MMC and ADR were comparatively active against the hepatoma cell, CDDP was less active than these 3 agents, CPA was inactive. These results seem to justify the use of current anticancer agents against hepatic cell carcinoma and indicate the usefulness of SRC assay for selecting chemotherapeutic agents against liver cell carcinoma.
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PMID:[Study on the chemosensitivity of liver cell carcinoma by subrenal capsule assay]. 334 29

Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas.
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PMID:Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion. 335 72

Twelve patients with unresectable hepatocellular carcinoma associated with cirrhosis were treated with Doxorubicin which was given intravenously (30 to 50 mg/m2) every three weeks. Six patients were given only one dose of Doxorubicin. No clinical response was observed. Five patients has serum alphafoetoprotein (AFP) determination during the treatment. AFP concentration rose in 4 patients and fell in 1 patient. Survival rate after 3 and 8 months of treatment was 58 and 33 per cent. These results suggest that Doxorubicin is not an effective treatment for hepatocellular carcinoma.
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PMID:[Hepatocellular carcinoma with cirrhosis: treatment with doxorubicin. Phase II evaluation]. 608 28

The effects of doxorubicin (Adriamycin) on regenerating liver were studied after two-thirds hepatectomy in rats. In Group I, standard two-thirds hepatectomy was performed. Doxorubicin in a dose of 2 mg/kg (Group II) and 6 mg/kg (Group III) was given intravenously immediately after the same hepatectomy. In Group IV, 6 mg/kg doxorubicin was given after sham operation. Animal survival, body weight restoration, wet weight and mitotic activity of remnant livers, and serum albumin concentrations were examined 1-14 days after operation. The survival rates were 95.5% in Group I, 76.8% in Group II, 10.3% in Group III, and 96.7% in Group IV. Although there were no differences in the residual liver weights among the hepatectomized groups, treatment with doxorubicin induced substantial, dose-dependent suppression and delay of liver cell division. Serum albumin levels dropped considerably in hepatectomized, doxorubicin-treated rats. Light microscopy showed degenerative changes with a single cell necrosis of hepatocytes in Group III. Death among rats hepatectomized and treated with doxorubicin was considered to be mainly due to the failure of residual livers since albumin synthesis was impaired and no marked changes were seen in vital organs other than the liver. For patients with hepatoma, the present results may indicate that the administration of adjuvant chemotherapy with doxorubicin, when necessary immediately after hepatectomy, should be performed with great care. In the absence of such necessity, doxorubicin should be withheld until life-sustaining liver regeneration has taken place.
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PMID:Effect of doxorubicin on liver regeneration and host survival after two-thirds hepatectomy in rats. 705 15

Doxorubicin (adriamycin), once considered the treatment of choice for hepatocellular carcinoma (HCC), is known to cause cardiotoxicity and myelotoxicity. To reduce the systemic toxicity of adriamycin by direct delivery of the drug to the tumor site, we established a panel of monoclonal antibodies (MAbs) to hepatoma associated antigens that were conjugated to adriamycin by a dextran bridge. Initially, the efficacy of these conjugates in suppressing tumor growth was assessed using a model of subcutaneous HCC tumors injected in athymic mice. In the second stage of the study, we tested these conjugates in an experimental model in which human HCC was transplanted intrahepatically by intrasplenic injection, thus providing the tumor cells with growth factors and an adequate cellular matrix, similar to the natural microenvironment of HCC. Anti-tumoral therapy resulted in lower serum alpha-fetoprotein (AFP) levels in two of three experimental groups treated with different specific conjugates as compared with control mice treated with the individual components. Efficacy of targeting was enhanced using the intrahepatic model system for propagation of HCC and was demonstrated by fluorescence of adriamycin and MAb in tumor tissue and absence of this fluorescence in healthy liver tissue surrounding the tumor. Reduction of systemic toxicity was shown by the absence of adriamycin fluorescence in myocardial tissue in conjugate-treated mice, whereas in all other treatment groups, including mice treated with a mixture of adriamycin and specific MAb, there was strong myocardial fluorescence of adriamycin.
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PMID:Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrahepatic tumors in athymic mice. 759 Jun 67


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