A phase II trial of pyrazine diazohydroxide in patients with disseminated malignant melanoma and no prior chemotherapy--Southwest Oncology Group study.
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.
Whitehead
Robert P
RP
University of Texas Medical Branch, Galveston, USA.
Unger
Joseph M
JM
Flaherty
Lawrence E
LE
Kraut
Eric H
EH
Mills
Glenn M
GM
Klein
Catherine E
CE
Chapman
Robert A
RA
Doolittle
Gary C
GC
Hammond
Neel
N
Sondak
Vernon K
VK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use* / Q000633:toxicity
D000970:Antineoplastic Agents; D011719:Pyrazines; C051397:pyrazine-2-diazohydroxide