[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)].
AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
D000328:Adult; D000368:Aged; D000609:Aminoacridines / Q000009:adverse effects / Q000627:therapeutic use*; D000677:Amsacrine; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine