everolimus + cyclophosphamide

Combination regimen of the mTOR inhibitor everolimus with low-dose metronomic cyclophosphamide evaluated primarily in metastatic renal cell carcinoma and other solid tumors to counteract everolimus-associated regulatory T cell expansion and enhance antitumor immunity. Everolimus inhibits mTORC1 to reduce tumor cell growth, proliferation, angiogenesis, and survival, but can expand immunosuppressive regulatory T cells; metronomic cyclophosphamide selectively depletes regulatory T cells, aiming to restore effector immune activity. In phase 1 studies, the recommended cyclophosphamide dose with everolimus 10 mg once daily was 50 mg once daily (continuous), showing Treg depletion, acceptable safety compared with everolimus alone, and predominantly stable disease with occasional partial responses in pretreated mRCC. A phase II evaluation and studies in prostate cancer explored similar low-dose schedules.

Other names

everolimus and cyclophosphamide