This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rivera, G. Articles by Pratt, C. B. Search for Related Content PubMed PubMed Citation Articles by Rivera, G. Articles by Pratt, C. B.

Phase I Clinical and Pharmacokinetic Study of 4'-(9-Acridinylamino)-methanesulfon-m-anisidide in Children with Cancer¹

St. Jude Children's Research Hospital, Memphis, Tennessee 38101

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 >100 mg/sq m/day were required to maintain serum concentrations of total and free AMSA >0.2 µM 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.

¹ This research was supported by Leukemia Program Project Grant CA 20180, by Solid Tumor Program Project Grant CA 23099, by Cancer Center Support Grant CA 21765, and by American Lebanese Syrian Associated Charities. Presented in part at the 81st Annual Meeting of the American Society for Clinical Pharacology and Therapeutics, San Francisco, Calif. 1980 (7).

² To whom requests for reprints should be addressed, at St. Jude Children's Hospital, 332 N. Lauderdale, P. O. Box 318, Memphis, Tenn. 38101.

Received 3/28/80. Accepted 7/10/80.