High dose simvastatin combined with standard chemotherapy in patients with refractory Multiple Myeloma: a phase II study

Simvastatin reduces VCAM-1 expression in human umbilical vein endothelial cells exposed to lipopolysaccharide

“…The human subject may be able to tolerate a much higher dosage of simvastatin in the clinical setting. In a dose-finding study of high-dose simvastatin combined with standard chemotherapy in patients with relapsed or refractory myeloma or lymphoma, simvastatin could be administered safely followed by standard chemotherapy with acceptable toxicity at a dose of 15 mg/kg for 7 days, which was almost 20 times the recommended therapeutic dosage [22]. Further experiments are required to elucidate the in-vivo effect of simvastatin on endothelial cells.…”

HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence?

“…Patients with relapsed multiple myeloma and non-Hodgkin lymphoma (NHL), who had been treated with at least two lines of chemotherapy, including anthracyclines, were treated with a dose-escalating regimen of simvastatin for 7 days followed by vincristine, adriamycin, and dexamethasone (VAD) in myeloma patients and cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) in NHL patients. High-dose simvastatin was administered with acceptable toxicity at a dose of 15 mg/kg for 7 days followed by standard chemotherapy [91]. The results of ongoing phase II trials on the use of statins in patients with refractory NHL and myeloma are awaited ( Table 2).…”

“…The optimal dosing regimen of statins when combined with other chemotherapies including anthracyclines was examined in a phase I dose escalation study [91]. Patients with relapsed multiple myeloma and non-Hodgkin lymphoma (NHL), who had been treated with at least two lines of chemotherapy, including anthracyclines, were treated with a dose-escalating regimen of simvastatin for 7 days followed by vincristine, adriamycin, and dexamethasone (VAD) in myeloma patients and cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) in NHL patients.…”

Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma

“…1,2 Some epidemiologic analyses have demonstrated up to a 50% reduction in cancer risk among statin users [3][4][5] and partial or complete responses have been observed in some, but not all, patients undergoing early phase 1/2 trials. [6][7][8][9][10][11][12] These mixed responses underscore the importance of reliably identifying the appropriate subset of patients who stand to benefit most from statin-based anticancer therapy. To ultimately advance statins as anticancer agents, it is therefore crucial to understand the molecular mechanisms involved in their anticancer activity and to delineate markers that distinguish the subset of tumors that are sensitive to statin-induced apoptosis.…”