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Cancer Treat Rep. 1982 May;66(5):1215-7.

Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses.


6-Diazo-5-oxo-L-norleucine (DON), an L-glutamine antagonist, was administered to 25 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 58 evaluable courses of five daily iv injections every 3-4 weeks were given, at doses ranging from 7.5 to 90 mg/m2/day. The major dose-limiting toxicity was a syndrome of nausea, vomiting, malaise, and anorexia, which became severe at doses greater than 52.5 mg/m2/day. Diarrhea and stomatitis were less frequent. Hematologic toxicity included mild leukopenia with nadir on Day 6-8 and mild thrombocytopenia with nadir on Day 7-12. Transient decreases in serum calcium to 8.5--8.9 mg/dl were seen in seven of 12 patients receiving greater than or equal to 67.5 mg/m2/day. Dose reduction was required for all patients who received a course of DON at greater than 67.5 mg/m2/day, and a maximum tolerated total dose of 250 mg/m2 (50 mg/m2/day x 5) is suggested for this schedule. Mixed responses were seen in one patient with bladder carcinoma and in one with pulmonary adenocarcinoma.

[Indexed for MEDLINE]

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