التفاصيل البيبلوغرافية
| العنوان: |
Phase I clinical and pharmacology study of 502U83 given as a 24-h continuous intravenous infusion. |
| المؤلفون: |
Schilsky, Richard, Ratain, Mark, Janisch, Linda, Vogelzang, Nicholas, Lucas, V., Ravitch, Joshua, Hohneker, John, Clendeninn, Neil, Tuttle, Richard, Schilsky, R L, Ratain, M J, Janisch, L, Vogelzang, N J, Lucas, V S, Ravitch, J, Hohneker, J A, Clendeninn, N J, Tuttle, R L |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Jul1993, Vol. 31 Issue 4, p283-288, 6p |
| مصطلحات موضوعية: |
ANTINEOPLASTIC agents, CLINICAL trials, COMPARATIVE studies, DOSE-effect relationship in pharmacology, ELECTROCARDIOGRAPHY, HIGH performance liquid chromatography, HYDROCARBONS, INTRAVENOUS therapy, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESPIRATORY insufficiency, TUMORS, EVALUATION research |
| مستخلص: |
502U83 is an arylmethylaminopropanediol that displays significant antitumor activity in a number of murine and human tumor-model systems. In the present phase I study, a 24-h continuous intravenous infusion of this agent was given every 28 days to patients with advanced or refractory solid tumors. In all, 46 patients received a total of 96 cycles of 502U83 at doses ranging from 25 to 8,000 mg/m2. No significant hematologic, gastrointestinal, or neurologic toxicity was observed. At doses of 2,000 mg/m2 and higher, prolongation of the corrected QT interval on ECG was evident in most patients but was completely reversible, was not associated with arrhythmias, and was not dose-limiting. Dose-limiting pulmonary toxicity characterized by acute onset of dyspnea, severe hypoxemia, interstitial pulmonary edema, and death occurred in three patients treated at the highest dose levels. Plasma concentrations of 502U83 and its metabolites were measured by high-performance liquid chromatography. The 502U83 maximal concentration (Cmax) and area under the concentration-time curve (AUC) were proportional to the delivered dose; however, substantial interpatient variability in total body clearance was noted at all dose levels. Significant conversion of 502U83 to two glucuronide metabolites was detected. Metabolite concentrations were highest in the three patients who succumbed to pulmonary toxicity, although the precise contribution of these metabolites to the observed toxic effects is unknown. In view of the unfavorable clinical profile of QTc prolongation and pulmonary toxicity produced by 502U83, further clinical development of this agent has been suspended. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancer Chemotherapy & Pharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Find this article in full text from Springer Verlag. 
Full Text Finder