Milan Slavik

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Daunomycin, like its anthracycline analog adriamycin, is a cardiotoxic antitumor antibiotic. Reports on 5,613 patients receiving daunomycin were reviewed for cardiotoxicity. Two distinct patterns of cardiotoxicity were defined, congestive heart failure (cardiomyopathy) and electrocardiographic changes. Dose-response curves were constructed using the percent(More)
alpha-Difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, blocks polyamine biosynthesis and has antitumor effects in animal tumor models as well as in athymic mice implanted with human small cell carcinoma. This study was designed to determine the maximally tolerated dose of oral DFMO administered every(More)
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%(More)
The limiting toxicity of low dose continuous infusion 5-fluorouracil (200–300 mg/m2/day) is often palmarplantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42% –82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity(More)
KVLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential that is defective in cardiac arrhythmia. The channel is inhibited by the chromanol 293B, a compound that blocks cAMP-dependent electrolyte secretion in rat and human colon, therefore suggesting expression of a similar type of K+ channel in the colonic(More)
Eflornithine-HCl (alpha-difluoromethylornithine or DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity in cell culture and animal tumor models. This phase I study was designed to determine and compare toxicity and the maximally tolerated dose of a 4-day course of DFMO given to(More)
Spirogermanium is a new azaspirane antitumor agent, with the metal germanium substituted for a one-carbon moiety in the ring structure. This drug inhibits DNA and RNA synthesis in HeLa cells, is cytotoxic in vitro, and has curative in vivo antitumor activity against the ascitic Walker 256 carcinosarcoma in rats. No hematologic toxicity was recorded during(More)
Taxol (paclitaxel)--the natural product isolated from Pacific yew (Taxus brevifolia)--is a novel agent with high activity in the treatment of patients with several malignant tumors including those resistant to other cytotoxic drugs. The therapeutic index of this promising anticancer drug could be further increased by the exploration of its pharmacokinetic(More)