Dose-finding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma.
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.
Department of Hematology and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Ellen
E
van der Spek
Andries C
AC
Bloem
Niels W C J
NW
van de Donk
Lijnie H
LH
Bogers
René
R
van der Griend
Mark H
MH
Kramer
Okke
O
de Weerdt
Shulamiet
S
Wittebol
Henk M
HM
Lokhorst
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D016879:Salvage Therapy; D019821:Simvastatin / Q000008:administration & dosage* / Q000633:toxicity; D016896:Treatment Outcome
D019821:Simvastatin