Phase II evaluation of DON (6-diazo-5-oxo-L-norleucine) in patients with advanced colorectal carcinoma
Abstract
Twenty-three patients with advanced colorectal carcinoma, previously treated with chemotherapy, were entered in a phase II trial of DON (6-Diazo-5-Oxo-l-Norleucine), an antagonist of l-glutamine. One of 14 adequately treated patients had a partial response of 6 weeks duration. The dose-limiting toxicity was nausea and vomiting; 48% of patients originally entered on the study withdrew because of vomiting. Myelosuppression was minimal, with only mild thrombocytopenia noted. The dose and schedule used in this study were beyond the maximally tolerated dose for many patients; future phase II studies of DON will be difficult to complete unless schedules and doses are found which result in less nausea and vomiting.
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DON was identified as a potential anti-cancer glutamine antagonist more than half a century ago, but its lack of substrate specificity caused too much off-target toxicity.
“6-Diazo-5-oxo-l-norleucine (DON) was identified as a potential anti-cancer glutamine antagonist more than a half century ago201, but its lack of substrate specificity provided too much off-target toxicity202.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [201]
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- Authors
- Lynch, G., Kemeny, N., & Casper, E.
- ORCID
- Kemeny, Nancy
- Venue
- American Journal of Clinical Oncology
- Published
- 1982-10
- Volume
- 5
- Issue
- 5
- Pages
- 541-543
- ISSN
- 0277-3732 (ISSN-L)
- OpenAlex
- W4255273898
- Cited by
- 53
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 3 · 2013: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- 6-diazo-5-oxo-L-norleucine, DON, advanced colorectal cancer, glutamine antagonist, chemotherapy, nausea and vomiting, myelosuppression, thrombocytopenia, dose-limiting toxicity, partial response
- MeSH terms
- Adult, Aged, Azo Compounds, Carcinoma, Colonic Neoplasms, Diazooxonorleucine, Drug Administration Schedule, Drug Evaluation, Humans, Middle Aged, Nausea, Rectal Neoplasms, Vomiting
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