PHASE I-II STUDY OF M-AMSA ADMINISTERED AS A CONTINUOUS INFUSION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (10) , 1813-1817
Abstract
In vitro studies of 4''-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) with L1210 [mouse] 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 h, 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 per day .times. 3, 30 mg/m2 per day .times. 4 or 40 mg/m2 day .times. 3. Myelosuppression was dose-limiting and occurred at .apprx. 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 per day .times. 3 in this 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 3 patients. Apparently, it is possible to give m-AMSA as a continuous infusion; 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.