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

Raez, LE, Papadopoulos, K, Ricart, AD et al. (2013). A phase i dose-escalation trial of 2-deoxy-d-glucose alone or combined with docetaxel in patients with advanced solid tumors . CANCER CHEMOTHERAPY AND PHARMACOLOGY, 71(2), 523-530. 10.1007/s00280-012-2045-1

cited authors

  • Raez, LE; Papadopoulos, K; Ricart, AD; Chiorean, EG; Dipaola, RS; Stein, MN; Rocha Lima, CM; Schlesselman, JJ; Tolba, K; Langmuir, VK; Kroll, S; Jung, DT; Kurtoglu, M; Rosenblatt, J; Lampidis, TJ

authors

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/m2 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. © 2012 Springer-Verlag Berlin Heidelberg.

publication date

  • February 1, 2013

published in

Digital Object Identifier (DOI)

start page

  • 523

end page

  • 530

volume

  • 71

issue

  • 2