title: Phase I clinical and pharmacokinetic study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in children with cancer.
abstract: Forty-one pediatric patients 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 five days every two to three weeks. In patients with leukemia: (a) dosages were escalated from 1.3 to 150 mg/sq m/day; (b) toxicity in the form of stomatitis, vomiting, and phlebitis occurred at dosage levels of 125 to 150 mg/sq m/day; and (c) oncolytic effects were observed in 13 of 24 patients. In patients with solid tumors: (a) dosages were escalated from 5 to 50 mg/sq m/day; (b) toxicity (stomatitis, myelosuppression, and phlebitis) occurred at the dosage level of 50 mg/sq m/day; and (c) 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 greater than 100 mg/sq m/day were required to maintain serum concentrations of total and free AMSA greater than 0.2 microM for the entire five-day schedule. The results suggest that maximum tolerated dosages of AMSA may differ in children with leukemia and solid tumors; however, hematopoietic toxicity could not be fully evaluated in the patients with leukemia. AMSA has clear antileukemic activity that warrants future Phase II trials.
mesh_terms: D000293:Adolescent; D000328:Adult; D000585:Aminacrine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D000609:Aminoacridines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007700:Kinetics; D007938:Leukemia / Q000188:drug therapy; D008657:Metabolic Clearance Rate; D009447:Neuroblastoma / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D013424:Sulfanilamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000609:Aminoacridines; D013424:Sulfanilamides; D000585:Aminacrine; C013389:4'-(9-acridinylamino)methanesulfonanilide