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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Vydáno v:	Cancer chemotherapy and pharmacology Ročník 71; číslo 2; s. 523 - 530
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer-Verlag 01.02.2013 Springer Springer Nature B.V
Témata:	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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	0344-5704 1432-0843 1432-0843
DOI:	10.1007/s00280-012-2045-1