Dose-finding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma

Department of Hematology and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. In vitro statins induce apoptosis in myeloma and lymphoma cells in a dose-and time-dependent way. In combination with dexamethasone and doxorubicin, statins have a chemo-sensitizing effect. Twenty-e...

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Bibliographic Details
Published in:Haematologica (Roma) 2006-04, Vol.91 (4), p.542-545
Main Authors: van der Spek, E, Bloem, AC, van de Donk, NW, Bogers, LH, van der Griend, R, Kramer, MH, de Weerdt, O, Wittebol, S, Lokhorst, HM
Format: Article
Language:English
Subjects:
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - toxicity
Biological and medical sciences
Hematologic and hematopoietic diseases
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma - complications
Lymphoma - drug therapy
Maximum Tolerated Dose
Medical sciences
Multiple Myeloma - complications
Multiple Myeloma - drug therapy
Recurrence
Salvage Therapy
Simvastatin - administration & dosage
Simvastatin - toxicity
Treatment Outcome
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Summary:Department of Hematology and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. In vitro statins induce apoptosis in myeloma and lymphoma cells in a dose-and time-dependent way. In combination with dexamethasone and doxorubicin, statins have a chemo-sensitizing effect. Twenty-eight patients with relapsed myeloma or lymphoma were treated with a dose-escalating regimen of simvastatin for 7 days followed by VAD in myeloma patients and CHOP in lymphoma patients. The maximum tolerated dose was 15 mg/kg/day simvastatin. The most frequently reported side-effects were fatigue, gastrointestinal CTC grade 1-2 and neutropenic fever. The dose-limiting toxicity was neutropenic sepsis and grade 3 gastrointestinal side effects. High-dose simvastatin given immediately prior to chemotherapy is safe and tolerable up to a dose of 15 mg/kg/day.
ISSN:0390-6078
1592-8721