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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1978-7-26
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pubmed:abstractText |
A phase I investigation of chlorozotocin, a new-water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty-three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose-dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t1/2S of 3, 15, and 30 min. The concentration of N-nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N-nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0009-9236
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
712-22
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:148344-Adolescent,
pubmed-meshheading:148344-Adult,
pubmed-meshheading:148344-Aged,
pubmed-meshheading:148344-Child,
pubmed-meshheading:148344-Clinical Trials as Topic,
pubmed-meshheading:148344-Drug Evaluation,
pubmed-meshheading:148344-Drug-Induced Liver Injury,
pubmed-meshheading:148344-Gastrointestinal Diseases,
pubmed-meshheading:148344-Hematologic Diseases,
pubmed-meshheading:148344-Humans,
pubmed-meshheading:148344-Kidney Diseases,
pubmed-meshheading:148344-Kinetics,
pubmed-meshheading:148344-Middle Aged,
pubmed-meshheading:148344-Neoplasm Metastasis,
pubmed-meshheading:148344-Streptozocin
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pubmed:year |
1978
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pubmed:articleTitle |
Phase I studies on chlorozotocin.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.
|