PHASE-I CLINICAL AND PHARMACOKINETIC STUDY OF 4'-(9-ACRIDINYLAMINO)-METHANESULFON-META-ANISIDIDE IN CHILDREN WITH CANCER

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (11) , 4250-4253
Abstract
Pediatric patients (41) with advanced cancer (24 with acute leukemia and 17 with diverse solid tumors) received 74 courses of therapy with a new chemotherapeutic agent, 4''-(9-acridinylamino)methanesulfon-m-anisidide (AMSA; NSC 249992). Treatments were given by slow i.v. injection daily for 5 days every 2-3 wk. In patients with leukemia, dosages were escalated from 1.3 to 150 mg/m2 per day; toxicity in the form of stomatitis, vomiting and phlebitis occurred at dosage levels of 125 to 150 mg/m2 per day; and oncolytic effects were observed in 13 of 24 patients. In patients with solid tumors, dosages were escalated from 5 to 50 mg/m2 day; toxicity (stomatitis, myelosuppression and phlebitis) occurred at the dosage level of 50 mg/m2 per day; and no oncolytic responses were noted. Serum concentrations of total and free AMSA were assayed by a fluorescence technique and declined in a biphasic manner with free AMSA declining more rapidly than total AMSA. Dosages of > 100 mg/m2 per day were required to maintain serum concentrations of total and free AMSA > 0.2 .mu.M for the entire 5 day schedule. Maximum tolerated dosages of AMSA may differ in children with leukemia and solid tumors. Hematopoietic toxicity could not be fully evaluated in the patients with leukemia. AMSA had clear antileukemic activity that warrants future Phase II trials.