Phase II study of pyrazine diazohydroxide (NSC 361456) for advanced non small-cell lung cancer.

Pyrazine diazohydroxide (NSC 361456) (PZDH) was selected for further development after demonstrating more stability than its parent compound and significant antitumor activity in a number of in vivo tumor models. Its proposed mechanism of action is through the formation of DNA adducts via the reactive pyrazine diazonium ion. The aim of this phase II trial was to determine the toxicity and antitumor activity of PZDH in advanced non small-cell lung cancer (NSCLC). From May 1995 through April 1996, 17 chemo-therapy-naive patients were entered into this study. PZDH was administered via a 5-minute intravenous bolus injection at a dose of 100 mg/m2 for 5 days and repeated every 42 days. Per interim guidelines, the study was closed early due to lack of activity. Seventeen patients were evaluable for toxicity while 15 patients were evaluable for response. The median number of cycles administered was 2 (range, 1-7). Toxicity was moderate with grade 3-4 thrombocytopenia being the most common and occurring in six of 17 patients. Of the 15 patients evaluable for response, no partial or complete responses were observed (95% confidence interval [CI]: 0%-22%), while seven patients had stable disease and eight patients progressed during therapy. All but one patient have died. The median survival for the group is 6.6 months (95% CI: 3.4-10.8 months). PZDH possesses modest but acceptable hematologic toxicity when delivered at the above dose and dosing scheme. Our results demonstrate that PZDH has no clinical activity in advanced NSCLC with this dose and schedule.