A phase II trial of pyrazine diazohydroxide in patients with disseminated malignant melanoma and no prior chemotherapy--Southwest Oncology Group study.

Abstract

Malignant melanoma is rapidly increasing in the United States. Metastatic disease responds poorly to currently available chemotherapy. Pyrazine diazohydroxide (PZDH) is a new agent inhibiting DNA synthesis that is active in mouse tumor models and human xenografts and lacks cross resistance with multiple standard agents. In this phase II trial, patients with no prior chemotherapy or immunotherapy for metastatic disease and performance status (SWOG) of 0-1, were treated with pyrazine diazohydroxide at a dose of 100 mg/m2/day by i.v. bolus injection over 5-15 minutes for 5 consecutive days every 6 weeks. There were 23 eligible patients entered on this trial with 74% having PS of 0 and 91% having visceral metastases. There were no confirmed anti-tumor responses. The overall response rate is 0% (95% CI 0%-15%). Median overall survival is six months (95% CI 5-8 months). The most common toxicities were hematologic and consisted of lymphopenia, thrombocytopenia, anemia, and leukopenia. Fatigue. and nausea and vomiting were the next most common toxicities. Pyrazine diazohydroxide by this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.

• Authors: Robert P Whitehead, Joseph M Unger, Lawrence E Flaherty, Eric H Kraut, Glenn M Mills, Catherine E Klein, Robert A Chapman, Gary C Doolittle, Neel Hammond, Vernon K Sondak, Southwest Oncology Group
• Journal: Investigational new drugs (Invest New Drugs) Vol. 20 Issue 1 Pg. 105-11 (Feb 2002) ISSN: 0167-6997 [Print] United States
• PMID: 12003185 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Pyrazines
• pyrazine-2-diazohydroxide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use, toxicity)
• Female
• Humans
• Injections, Intravenous
• Male
• Melanoma (drug therapy, secondary)
• Middle Aged
• Pyrazines (therapeutic use, toxicity)