title: A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The recommended dose of 2DG in combination with weekly docetaxel is 63 mg/kg/day with tolerable adverse effects.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, PO Box 016960, Miami, FL 33101, USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Papadopoulos
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Ricart
authors.forename: E Gabriella
authors.initials: EG
authors.lastname: Chiorean
authors.forename: Robert S
authors.initials: RS
authors.lastname: Dipaola
authors.forename: Mark N
authors.initials: MN
authors.lastname: Stein
authors.forename: Caio M
authors.initials: CM
authors.lastname: Rocha Lima
authors.forename: James J
authors.initials: JJ
authors.lastname: Schlesselman
authors.forename: Khaled
authors.initials: K
authors.lastname: Tolba
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Langmuir
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: Donald T
authors.initials: DT
authors.lastname: Jung
authors.forename: Metin
authors.initials: M
authors.lastname: Kurtoglu
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenblatt
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Lampidis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003847:Deoxyglucose / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D043823:Taxoids; D000077143:Docetaxel; D003847:Deoxyglucose