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Biomedical subjects

H G Chun

Publications and source records attributed to H G Chun.

28 records · Page 2Linked to original sources
PubMed1987

Merbarone: an antitumor agent entering clinical trials.

Merbarone was developed to clinical trial stage on the basis of its 'curative' activity against P388 and L1210 leukemias and moderate activity against B16 melanoma and M5076 sarcoma. Its activity appears to be schedule-dependent favoring a longer duration of administration. The mechanism of action of merbarone is not yet established but it does induce single strand breaks in DNA apparently without binding to DNA. The pharmacokinetic data in the dog indicate that clearance mechanisms may be saturable. Merbarone is hydroxylated at the 4' position in the rat, mouse and dog, and glucuronidated in the dog. Parent drug and the hydroxy metabolite are excreted in the urine. If saturable clearance mechanisms also pertain to man, this will mean that infusion rate (and therefore steady state concentrations reached) may be a significant factor in determining acute toxicity. Preclinical toxicology studies revealed that major target tissues are in the lymphoid organs, bone marrow, gastrointestinal tract and kidney. Some behavioral signs of reversible central nervous system toxicity were observed. Phase I trials have commenced using only a 5-day continuous intravenous infusion schedule based on the preclinical data. The pharmacokinetic information from these trials will be crucial for further clinical development of the compound, including selection of the optimal schedule(s) for phase II/III evaluation.

Animals↗
PubMed1986

Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent.

A new class of marine compounds, the didemnins, with potent antitumor activity has been identified. They share the novel structure of a cyclic depsipeptide. Among three structurally related compounds, didemnin B is by far the most potent in its in vitro cytotoxicity and in vivo antitumor activity (0.001 microgram/ml inhibits the growth of L1210 leukemia cells by 50%). It also demonstrates good antitumor activity against B16 melanoma and moderate activity against M5076 sarcoma and P388 leukemia. The compound also has good antiviral and potent immunosuppressive properties. Although the precise mechanism of action for the cytotoxicity remains unknown, the agent inhibits protein synthesis more than DNA synthesis and the inhibition of protein synthesis is closely correlated with inhibition of L1210 cell growth. Toxicology studies in CD2F1 mice, Fischer 344 rats and beagle dogs reveal that major target organs are the lymphatics, gastrointestinal tract, liver and kidney. Phase I trials are currently in progress under the auspices of the National Cancer Institute.

Animals↗
PubMed1986

Central nervous system toxicity of fludarabine phosphate.

Fourteen patients developed severe central nervous system (CNS) toxicity after receiving an investigational antitumor agent, fludarabine phosphate (FAMP). The CNS toxicity has the distinctive features of delayed onset and progressive clinical course. Visual deficits were the most common presenting symptom and developed eventually in most cases. Deterioration of mental status and progressive encephalopathy were also observed. The development of clinical CNS toxicity appears dose-related; thirteen of 36 patients (36.1%) who received FAMP at high doses (greater than or equal to 96 mg/m2/day for 5-7 days per course) developed neurotoxicity, while only one of 443 patients (0.2%) who received the drug at low doses (less than or equal to 125 mg/m2 per course) developed similar toxicity. Although the precise mechanism responsible for this toxicity is yet unknown, progressive demyelination appears to be the responsible process. Extensive review of the clinical data failed to identify factors which might contribute to the development of CNS toxicity. Patients on trials of FAMP should be meticulously monitored for the possible development of neurotoxicity.

Acute Disease↗
PubMedDate not supplied

Azacitidine: 10 years later.

Azacitidine has been undergoing clinical trials for almost 20 years and is internationally considered to have a useful place in the treatment of acute nonlymphocytic leukemia. However, its role in the various combinations for induction, intensification, maintenance, or relapse regimens has not yet been clearly defined. This review outlines the last 10 years' clinical experience with the drug in acute nonlymphocytic leukemia, analyzes what critical information has yet to be obtained, and suggests what phase III trials may still be feasible to gather that information.

Acute Disease↗