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Phase II evaluation of the AMAP, 773U82 mesylate, in pancreatic cancer
D L Trump1, J A Hathorn, L B Grochow
1Pittsburgh Cancer Institute, Montefiore University Hospital, PA 15213-3241, USA.
Abstract:
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.
Insights
This study investigated 773U82 mesylate for pancreatic cancer treatment. The drug showed no significant response in patients, indicating it is not an effective therapy for this disease.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pancreatic cancer is a leading cause of cancer death in the US, with limited effective systemic therapies.
- 773U82 mesylate, an arylmethylaminopropanediol (AMAP), demonstrated DNA binding and topoisomerase 2 inhibition in preclinical studies.
Purpose of the Study:
- To evaluate the efficacy and toxicity of 773U82 mesylate in a Phase II clinical trial for patients with pancreatic cancer.
Main Methods:
- A multi-institutional Phase II trial administered 773U82 mesylate (800 mg/m2 daily x 3 infusion every 3 weeks) to eligible patients with pancreatic adenocarcinoma.
- Eligibility criteria included histologic proof, good performance status, and normal organ function.
Main Results:
- No objective response was observed in the 13 fully evaluable patients.
- Median time to progressive disease was 56 days among eligible patients.
- The primary toxicity observed was myelosuppression, which was manageable.
Conclusions:
- 773U82 mesylate did not demonstrate efficacy in treating pancreatic cancer.
- Further investigation of AMAPs in pancreatic cancer is not warranted based on these findings.