This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rizzieri, D. A. Articles by Moore, J. O. Search for Related Content PubMed PubMed Citation Articles by Rizzieri, D. A. Articles by Moore, J. O. Social Bookmarking                            What's this?

Phase I Evaluation of Prolonged-Infusion Gemcitabine With Mitoxantrone for Relapsed or Refractory Acute Leukemia

From the Division of Medical Oncology and Transplantation, Duke University Medical Center, and Duke Oncology Consortium, Durham, NC.

Address reprint requests to David A. Rizzieri, MD, Division of Medical Oncology and Transplantation, Duke University Medical Center, Box 3961, Durham, NC 27710; email: rizzi003{at}mc.duke.edu

PURPOSE: To ascertain the maximum tolerated duration of infusion of gemcitabine at 10 mg/m²/min in combination with mitoxantrone at 12 mg/m² daily for 3 days in the treatment of acute leukemia.

PATIENTS AND METHODS: Thirty-four patients were enrolled. Stratum I consisted of 26 patients, median age 50 years (range, 25 to 71 years), with relapsed or refractory leukemia. Stratum II contained eight patients, median age 62.5 years (range, 38 to 83 years), who had received fewer than three cycles of myelotoxic therapy for chronic myeloid leukemia or myelodysplasia that had evolved into leukemia. Patients received mitoxantrone at 12 mg/m² daily for 3 days. After the first mitoxantrone dose, gemcitabine was provided intravenously at 10 mg/m²/min with the duration adjusted by following a continuous reassessment model.

RESULTS: Severe myelosuppression, and stomatitis or esophagitis were the most common hematologic and nonhematologic dose-limiting toxicities. Several patients developed febrile neutropenia, nausea, or vomiting. In both strata, the maximum recommended duration of infusion of gemcitabine was 12 hours (7,200 mg/m²). The mean steady-state concentration of gemcitabine was 24.72 µmol/L and varied over a fivefold range among patients. Overall response rates in this phase I trial for strata I and II were 42% and 63%, respectively.

CONCLUSION: Prolonged-infusion gemcitabine at a fixed dose rate of 10 mg/m²/min for 12 hours with 12 mg/m²/d mitoxantrone for 3 days is a tolerable induction regimen and achieves plasma concentrations sufficient for maximal intracellular activation. Stomatitis or esophagitis should be anticipated; however, this regimen may induce significant responses in patients with difficult-to-treat leukemias.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. A. Veltkamp, J. H. Beijnen, and J. H.M. Schellens Prolonged Versus Standard Gemcitabine Infusion: Translation of Molecular Pharmacology to New Treatment Strategy Oncologist, March 1, 2008; 13(3): 261 - 276. [Abstract] [Full Text] [PDF]

				R. H. Shanks, D. A. Rizzieri, J. L. Flowers, O. M. Colvin, and D. J. Adams Preclinical Evaluation of Gemcitabine Combination Regimens for Application in Acute Myeloid Leukemia Clin. Cancer Res., June 1, 2005; 11(11): 4225 - 4233. [Abstract] [Full Text] [PDF]

				V. Gandhi, H. Kantarjian, S. Faderl, P. Bonate, M. Du, M. Ayres, M. B. Rios, M. J. Keating, and W. Plunkett Pharmacokinetics and Pharmacodynamics of Plasma Clofarabine and Cellular Clofarabine Triphosphate in Patients with Acute Leukemias Clin. Cancer Res., December 15, 2003; 9(17): 6335 - 6342. [Abstract] [Full Text] [PDF]

				D. A. Rizzieri, V. K. Ibom, J. O. Moore, C. M. DeCastro, G. L. Rosner, D. J. Adams, T. Foster, N. Payne, M. Thompson, J. J. Vredenburgh, et al. Phase I Evaluation of Prolonged-infusion Gemcitabine with Fludarabine for Relapsed or Refractory Acute Myelogenous Leukemia Clin. Cancer Res., February 1, 2003; 9(2): 663 - 668. [Abstract] [Full Text] [PDF]

				V. Gandhi, W. Plunkett, M. Du, M. Ayres, and E. H. Estey Prolonged Infusion of Gemcitabine: Clinical and Pharmacodynamic Studies During a Phase I Trial in Relapsed Acute Myelogenous Leukemia J. Clin. Oncol., February 1, 2002; 20(3): 665 - 673. [Abstract] [Full Text] [PDF]