Phase II evaluation of the AMAP, 773U82 mesylate, in pancreatic cancer.

Pancreatic cancer is the fifth leading cause in cancer related death among adults in the United States. Thirty-thousand new cases of pancreatic cancer are diagnosed each year, most are metastatic at diagnosis and no effective systemic therapy is available. 773U82 mesylate is one of a series of compounds (arylmethylaminopropanediols-AMAPS) which was synthesized at the Wellcome Research Laboratories. AMAPS bind to DNA, show evidence of topoisomerase 2 inhibition and are active in a variety of murine and human preclinical screens. Based on these data a phase II trial of 773U82 mesylate administered at 800 mg/m2 daily x 3 at a 4 h infusion repeated every three weeks was carried out. Patients eligible for these trials had histologic proof of adenocarcinoma, good performance status, and normal organ function. This was a multi-institutional trial. Nineteen patients were entered; 15 patients were fully eligible and 4 were ineligible, but were evaluated. Thirteen patients were fully evaluable for response and no response was seen. Median time to progressive disease among eligible patients was 56 days. Toxicity of 773U82 mesylate was myelosuppression which was not prohibitive. 773U82 mesylate is not active in pancreatic cancer.