Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia. Leukemia & lymphoma [Leuk Lymphoma] Journal article | | Title | Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia. | | Author(s) | Rao AV, Younis IR, Sand GJ, Spasojevic I, Adams DJ, Decastro CM, Gockerman JP, Peterson BL, Petros WP, Moore JO, Rizzieri DA | | Institution | Department of Medicine, Divisions of Medical Oncology, Pharmacology, and Cellular Therapy, Duke University Medical Center, Durham, NC, USA. | | Source | Leuk Lymphoma 2008 Aug; 49(8):1523-9. | | Abstract | Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with refractory or relapsed acute myeloid leukaemia (AML). Gemcitabine was administered at 10 mg/m(2)/min for 3-15 h, fludarabine at 25 mg/m(2) daily for days 1-5 and mitoxantrone at 10 mg/m(2) daily on days 1-3. PK studies revealed that fludarabine clearance was not affected by gemcitabine but mean terminal half-life and volume of distribution of fludarabine were slightly increased. The duration of MTD for gemcitabine was 12 h. Our previous in vitro work has demonstrated the binary combination of gemcitabine + fludarabine is most synergistic at a molar ratio around 0.002. However, with MTD dosing this drug ratio is not optimal to produce synergy and future studies using ratiometric dosing are required to confirm these findings. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 18766965 |
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