Phase I-II study of m-AMSA administered as a continuous infusion. 1982

K C Micetich, and L A Zwelling, and P Gormley, and R C Young

In vitro studies of 4'(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) with L1210 leukemia cells have demonstrated that a given level of DNA breakage and intraceLlular m-AMSA concentration depends upon the presence of a continuous concentration of extracellular drug and that cytotoxicity increases with an increasing duration of drug exposure. Since previous studies had shown that free m-AMSA has a half-life of 6-8 hours, a trial of m-AMSA given as a continuous infusion was undertaken in patients with solid tumors and lymphomas. Patients were treated with 30 mg/m2/day x 3, 30 mg/m2/day x 4, or 40 mg/m2/ day x 3. Myelosuppression was dose-limiting and occurred at about Day 13 after the start of the infusion. Recovery was noted by Day-21. There was no evidence of cumulative hematologic toxicity. The maximally tolerated dose was 30 mg/m2/day x 3 in our patient population. Mild phlebitis occurred in all patients. There were no instances of gastrointestinal, hepatic, renal, cardiac, or neurologic toxic reactions. Evidence of some antitumor effect was seen in three patients. We conclude that it is possible to given m-AMSA as a continuous infusion and that studies should be undertaken in patients with acute myelogenous leukemias to compare the efficacy of m-AMSA infusion with conventional bolus administration as a means to enhance the duration of response.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010689 Phlebitis Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS). Periphlebitis,Periphlebitides,Phlebitides
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000609 Aminoacridines Acridines which are substituted in any position by one or more amino groups or substituted amino groups.

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