Phase I study of methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-(m-AMSA) using a single-dose schedule.

Methanesulfonamide, N-[4-(9-acridinylamino)-30methoxyphenyl]-(NSC-249992), an acridine derivative with significant antitumor activity in animal tumor systems, was administered to 29 patients in a phase I clinical trial. The dose ranged from 10 to 160 mg/m2 with a single dose given every 28 days. The toxic effects included moderate to severe leukopenia and mild thrombocytopenia. Myelosuppression was more severe in patients with prior whole abdominal or pelvic radiotherapy. Superficial phlebitis occurred when the drug was diluted in a volume of less than 500 ml of 5% dextrose in water. Antitumor activity was detected in one patient with ovarian carcinoma. Phase II studies are indicated with this compound since it has reproducible and reversible toxicity with some evidence of antitumor activity. The starting dose of the drug for phase II trials should be 120 mg/m2 as a single iv dose repeated at 4-week intervals.