A phase I dose-escalation trial of 2-deoxy-d-glucose alone or combined with docetaxel in patients with advanced solid tumors

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 us...

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Published in:Cancer chemotherapy and pharmacology Vol. 71; no. 2; pp. 523 - 530
Main Authors: Raez, Luis E., Papadopoulos, Kyriakos, Ricart, Alejandro D., Chiorean, E. Gabriella, DiPaola, Robert S., Stein, Mark N., Rocha Lima, Caio M., Schlesselman, James J., Tolba, Khaled, Langmuir, Virginia K., Kroll, Stewart, Jung, Donald T., Kurtoglu, Metin, Rosenblatt, Joseph, Lampidis, Theodore J.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer-Verlag 01.02.2013
Springer
Springer Nature B.V
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Blood Glucose - analysis
Cancer Research
Clinical Trial Report
Deoxyglucose - administration & dosage
Deoxyglucose - adverse effects
Deoxyglucose - therapeutic use
Electrocardiography - drug effects
Female
Gynecology. Andrology. Obstetrics
Humans
Male
Mammary gland diseases
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neoplasms - drug therapy
Oncology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pneumology
Taxoids - administration & dosage
Taxoids - adverse effects
Taxoids - therapeutic use
Tumors
Tumors of the respiratory system and mediastinum
Phase I
Head and neck cancers
Lung cancer
Docetaxel
Breast cancer
2-Deoxy
Glucose
Antineoplastic agent
Solid tumor
Breast disease
Dose escalation
Bronchopulmonary
Increasing dose
Taxane derivatives
ENT disease
Bronchus disease
Clinical trial
Advanced stage
Antimitotic
Human
Lung disease
Respiratory disease
Malignant tumor
Mammary gland diseases
2-Deoxy-D-Glucose
Head and neck cancer
Cancer
ISSN:0344-5704, 1432-0843, 1432-0843
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Summary: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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ISSN:0344-5704
1432-0843
1432-0843
DOI:10.1007/s00280-012-2045-1