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

R. H. Earhart, J. M. Koeller, H. L. Davis

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 > 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 decrease in serum calcium to 8.5-8.9 mg/dl were seen in seven of 12 patients receiving ≥67.5 mg/m2/day. Dose reduction was required for all patients who received a course of DON at > 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.

Original languageEnglish (US)
Pages (from-to)1215-1217
Number of pages3
JournalCancer Treatment Reports
Volume66
Issue number5
StatePublished - 1982
Externally publishedYes

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Diazooxonorleucine
Stomatitis
Maximum Tolerated Dose
Leukopenia
Anorexia
Glutamine
Thrombocytopenia
Nausea
Vomiting
Diarrhea
Appointments and Schedules
Urinary Bladder
Calcium
Carcinoma
Injections
Serum
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Earhart, R. H., Koeller, J. M., & Davis, H. L. (1982). Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses. Cancer Treatment Reports, 66(5), 1215-1217.

Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses. / Earhart, R. H.; Koeller, J. M.; Davis, H. L.

In: Cancer Treatment Reports, Vol. 66, No. 5, 1982, p. 1215-1217.

Research output: Contribution to journalArticle

Earhart, RH, Koeller, JM & Davis, HL 1982, 'Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses', Cancer Treatment Reports, vol. 66, no. 5, pp. 1215-1217.
Earhart, R. H. ; Koeller, J. M. ; Davis, H. L. / Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses. In: Cancer Treatment Reports. 1982 ; Vol. 66, No. 5. pp. 1215-1217.
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