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 inthe United States. Metastatic diseaseresponds poorly to currently availablechemotherapy. Pyrazine diazohydroxide(PZDH) is a new agent inhibiting DNAsynthesis that is active in mouse tumormodels and human xenografts and lackscross resistance withmultiple standard agents. In this phase IItrial, patients with no prior chemotherapyor immunotherapyfor metastatic disease and performancestatus (SWOG) of 0–1, were treated withpyrazine diazohydroxide at a dose of 100 mg/m 2 /day by IV bolus injectionover 5–15 minutes for 5 consecutive daysevery 6 weeks. There were 23 eligiblepatients entered on this trial with 74%having PS of 0 and 91% having visceralmetastases. There were no confirmed anti-tumor responses. Theoverall response rate is 0% (95% CI 0%–15%). Median overall survival is sixmonths (95% CI 5-8months). The most common toxicities were hematologic and consisted of lymphopenia,thrombocytopenia, anemia, and leukopenia. Fatigue, and nausea and vomiting were thenext mostcommon toxicities. Pyrazine diazohydroxideby this dose and schedule has insufficientactivity in thetreatment of disseminated malignantmelanoma to warrant further investigation.