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Biomedical subjects

M Slavik

Publications and source records attributed to M Slavik.

At least 91 records · Page 5Linked to original sources
PubMed1976

Neocarzinostatin (NSC 157365) a new cancerostatic compound.

Neocarzinostatin is a new anticancer drug developed by Japanese investigators. In order to delineate the potential usefulness of this drug, we have reviewed the preclinical data and summarized the Japanese clinical data on 462 patients. The bulk of these patients had carcinoma of the stomach or pancreas and acute leukemia. Neocarzinostatin was administered intravenously in a daily dose of 2-3 mg for five to 15 day periods. Significant antitumor activity was observed in acute leukemia. A few responses were also reported in pancreatic adenocarcinoma, but the drug was inactive against gastric carcinoma. The side effects observed included nausea, vomiting, myelosuppression, fever, and occasional hypersensitivity reactions. The Investigational Drug Branch of the National Cancer Institute has recently sponsored an investigational new drug application with the Food and Drug Administration, and phase I studies are expected to begin soon in the United States.

Amino Acids↗
PubMed1976

5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia.

Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.

Animals↗
PubMed1975

Clinical comparison of the nitrosoureas.

The nitrosourea group of antitumor agents was developed by the Division of Cancer Treatment of the National Cancer Institute. Three nitrosoureas (BCNU, CCNU, MeCCNU) have undergone extensive clinical trials, and two of them (BCNU, CCNU) will soon become commercially available. This paper briefly considers the preclinical development of the nitrosoureas and provides an overview and comparison of the extensive clinical data. Information is given regarding any clinical differences. We discuss general conclusions drawn from the nitrosourea development.

Animals↗
PubMed1975

Changes in preference for NaCl following administration of 6-azauridine and 6-azauridine triacetate.

Preliminary evidence in man has suggested that 6-azauridine triacetate (6-AzUrdTA) might adversely affect taste acuity. The production of measurable serum concentrations of homocysteine in rabbits treated with 6-AzUrdTA further suggested a mechanism for the possible adverse effects of this drug on taste, since administration of other thiol-containing drugs in man and animals had been shown to decrease taste acuity. Since changes in preferences for NaCl solutions have been shown to reflect changes in taste acuity in the rat, preference for NaCl solutions in rats treated with 6-AzUrdTA were measured in a two-bottle test. Detection and recognition thresholds were also measured in patients with scleroderma before and after the administration of 6-AzUrdTA. Serum copper and zinc concentrations were measured in both rats and man. Rats given 6-AzUrdTA exhibited a significantly greater intake of 0.30-M NaCl than control rats, who avoided this solution. This change was accompanied by a significant decrease in serum zinc concentrations. No significant changes in taste acuity occurred in the patients. These data suggest that administration of 6-AzUrdTA affects taste acuity in rats either through the addition of thiols or the depletion of zinc.

Administration, Oral↗
PubMed1975

Quantitative prediction of drug toxicity in humans from toxicology in small and large animals.

The mouse, dog, and monkey toxicity data on 30 drugs was retrospectively analyzed in comparison with the actual clinical dose schedules used in man. Animal dose schedules were converted to the human schedule and comparisons were made of the human dose versus the large animal toxic dose low, toxic dose high, and lethal dose, the lethal doses for 10% and 90% of normal mice, and the optimal dose in tumor-bearing mice. If the starting dose in Phase 1 clinical trials had been selected by calculating one-third of the toxic dose low (in mg/sq m) in the most sensitive large animal species, 5 of the 30 drugs would have produced significant toxicity in the first patient. The lethal doses for 10 and 90% of normal mice and the optimal dose in L1210-bearing mice were found to offer good quantitative prediction of human toxicity. Determination of a safe and practical starting dose for Phase 1 studies should take into account not only dog and monkey data but also toxicology data in normal and tumor-bearing mice.

Animals↗