Journal
LEUKEMIA RESEARCH
Volume 33, Issue 11, Pages 1475-1480Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.01.039
Keywords
Multiple myeloma; mTOR; Temsirolimus; Pharmacokinetics
Categories
Funding
- National Cancer Institute of the United States [R21 CA11289, UO1 CA76576]
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In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25 mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3-4 toxicity included fatigue (n = 3), neutropenia (n = 2), thrombocytopenia (n = 2), interstitial pneumonitis(n = 1), stomatitis (n = 1) and diarrhea (n = 1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70(S6)K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. investigation of alternate dosing schedules and use in combinations is indicated. (C) 2009 Elsevier Ltd. All rights reserved.
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