Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.
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PMID:Phase I trial and clinical pharmacology of elsamitrucin. 154 Sep 49

Elsamitrucin (BMY-28090) a novel fermentation product has demonstrated pre-clinical anti-tumour activity against a number of cell lines. The dose limiting toxicity in phase I studies was a reversible increase in hepatic transaminase. This study was initiated to determine the activity of elsamitrucin in patients with previously untreated, bi-dimensionally measurable, cytologically or histologically proven, non-small cell lung cancer who were not curable by surgery. Elsamitrucin at a dose of 25 mg/m2 was administered intravenously over 5-10 min weekly for a minimum of 6 weeks. Seventeen patients were entered on study, 15 were evaluable for toxicity and 14 evaluable for response. No responses were documented in the 14 patients evaluable for response. Both hematological and non-hematological toxicities were mild to moderate in severity. The commonest being nausea, vomiting, lethargy and local skin reactions at the site of the infusion. These results indicate that elsamitrucin when given in this dose and schedule to patients with surgically incurable non-small cell lung cancer has no activity.
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PMID:Phase II study of elsamitrucin in non-small cell lung cancer. 777 32