A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors
Abstract
Purpose This phase I trial was initiated to evaluate the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) in combination with docetaxel, in patients with advanced solid tumors.Methods A modified accelerated titration design was used. 2DG was administered orally once daily for 7 days every other week starting at a dose of 2 mg/kg and docetaxel was administered intravenously at 30 mg/m(2) for 3 of every 4 weeks beginning on day 1 of week 2. Following the completion of dose escalation, cohorts of patients were then treated with 2DG for 21 days or every day of each 4-week cycle for up to 12 cycles.Results Thirty-four patients were enrolled: 21 on every other week, 6 on a 21 of 28-day cycle and 7 on the continuous 2DG dosing schedule. There were no dose-limiting toxicities which met the MTD criteria. The most common adverse events were fatigue, sweating, dizziness and nausea mimicking the hypoglycemic symptoms expected from 2DG administration. Therefore, 63 mg/kg was selected as the clinically tolerable dose. The most significant adverse effects noted at 63-88 mg/kg doses were reversible hyperglycemia (100 %), gastrointestinal bleeding (6 %) and reversible grade 3 QTc prolongation (22 %). Eleven patients (32 %) had stable disease, 1 patient (3 %) partial response and 22 patients (66 %) progressive disease as their best response. There was no PK interaction between 2DG and docetaxel.Conclusion The recommended dose of 2DG in combination with weekly docetaxel is 63 mg/kg/day with tolerable adverse effects.
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Recent clinical trials revisited 2-DG at lower doses, but these doses are insufficient to inhibit disease progression.
“Recent clinical trials have revisited use of 2-DG at lower doses, but these doses are insufficient to inhibit disease progression (Raez et al., 2013; Stein et al., 2010).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Raez et al., 2013
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- Authors
- Raez, L. E., Papadopoulos, K., Ricart, A. D., Chiorean, E. G., DiPaola, R. S., Stein, M. N., Rocha Lima, C. M., Schlesselman, J. J., Tolba, K., Langmuir, V. K., Kroll, S., Jung, D. T., Kurtoglu, M., Rosenblatt, J., & Lampidis, T. J.
- Affiliations
- University of Miami (US)
- The University of Texas at San Antonio Health Science Center (US)
- Rutgers, The State University of New Jersey (US)
- Threshold Pharmaceuticals (United States) (US)
- ORCID
- Venue
- Cancer Chemotherapy and Pharmacology
- Published
- 2012-12-11
- Volume
- 71
- Issue
- 2
- Pages
- 523-530
- ISSN
- 0344-5704 (ISSN-L)
- 1432-0843
- OpenAlex
- W1997909566
- Cited by
- 543
- References
- 30
- Citations by year
- 2026: 52 · 2025: 63 · 2024: 60 · 2023: 43 · 2022: 54 · 2021: 47 · 2020: 40 · 2019: 35 · 2018: 26 · 2017: 33 · 2016: 30 · 2015: 29 · 2014: 19 · 2013: 11 · 2012: 1
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Chemotherapy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- 2-deoxyglucose, docetaxel, glycolysis inhibitors, advanced solid tumors, maximum tolerated dose, dose escalation, pharmacokinetics, drug safety, hyperglycemia, QTc prolongation, gastrointestinal bleeding, combination chemotherapy
- MeSH terms
- Docetaxel, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Blood Glucose, Deoxyglucose, Electrocardiography, Female, Humans, Male, Middle Aged, Neoplasms, Taxoids
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