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

Patients affected by hepatocellular carcinoma (HCC) with unfavorable prognostic factors have limited therapeutic options due to moderate responsiveness to chemotherapeutic agents and lack of compliance with such treatments. In this study the feasibility and efficacy were evaluated of a treatment with mitoxantrone(dihydroxyanthracenedione, DHAD), 12 mg/m2 i.v. on day 1 every 3 weeks. We included 18 patients with poor-risk HCC ineligible for our other trials in relation to their performance status [8], pretreatments [6], age over 70 years [5], severe concomitant illness [6], and altered blood count [platelets less than 100,000/mm3) [8]. Of 17 evaluable cases, there were 4 partial remissions (23%) (95% confidence interval, 10-47%), 6 no changes, and 7 progressions. There were no drug-related deaths, and side effects were moderate and documented only in a few cases. Median survival of evaluable patients was 5 months (range, 1-15). The results were comparable with those obtained with adriamycin but without important toxicity. We conclude that DHAD seems to be safe and moderately active in poor-risk HCC.
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PMID:Mitoxantrone in patients affected by hepatocellular carcinoma with unfavorable prognostic factors. 131 28

The cytotoxic properties of quinone drugs such as menadione and adriamycin are thought to be mediated through one-electron reduction to semiquinone free radicals. Redox cycling of the semiquinones results in the generation of reactive oxygen species and in oxidative damage. In this study the toxicity of mitozantrone, a novel quinone anticancer drug, was compared with that of menadione in human Hep G2 hepatoma cells. Mitozantrone toxicity in these cells was not mediated by the one-electron reduction pathway. In support of this, inhibition of the enzymes glutathione reductase and catalase, responsible for protecting the cells from oxidative damage, did not affect the response of the Hep G2 cells to mitozantrone, whereas it exacerbated menadione toxicity. In addition, the toxicity of menadione was preceded by depletion of reduced glutathione which was probably due to oxidation of the glutathione. Mitozantrone did not cause glutathione depletion prior to cell death. DT-diaphorase activity and intracellular glutathione were found to protect the cells from the toxicity of both quinones. Inhibition of epoxide hydrolase potentiated mitozantrone toxicity but did not affect that of menadione. Our experiments indicate that mitozantrone toxicity may involve activation to an epoxide intermediate. Both quinone drugs inhibited cytochrome P-450-dependent mixed-function oxidase activity, although menadione was more potent in this respect.
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PMID:The toxicity of menadione and mitozantrone in human liver-derived Hep G2 hepatoma cells. 253 22

Thirty-five patients with hepatocellular carcinoma (HCC) have been treated with the Anthracenedione derivative, Mitozantrone. One complete and 5 partial responses were seen in 22 evaluable patients and in a further 4 patients tumour size remained static for lengths of time ranging from 13 to 42 weeks. Therapy was well tolerated. Bone marrow suppression was dose-limiting but easily managed by dose reduction. Other acute toxicity was rare, vomiting and hair loss being reported only once each. Cardiac 'events' occurred in 5 patients, 3 of whom had received high total cumulative doses of Mitozantrone. We conclude that Mitozantrone is of clinical benefit in HCC and that its usage is compatible with a good quality of survival. Its cardiotoxic potential requires further evaluation.
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PMID:Mitozantrone as single agent therapy in hepatocellular carcinoma. A phase II study. 299 22