sirolimus + cyclophosphamide + methotrexate + zoledronic acid

This is an investigational combination therapy regimen consisting of the mTOR inhibitor sirolimus, metronomic (low-dose continuous) chemotherapy agents cyclophosphamide and methotrexate, and the bone-targeting bisphosphonate zoledronic acid. Developed by Institut Bergonié and evaluated in the METZOLIMOS trial, the regimen is designed to treat advanced solid tumors with bone metastases and advanced pretreated osteosarcoma. The rationale for this combination is based on preclinical data suggesting synergistic effects on both the tumor microenvironment and cancer cells, particularly by targeting the bone niche. Sirolimus acts as a targeted inhibitor of the PI3K/Akt/mTOR pathway, while the metronomic dosing of cyclophosphamide and methotrexate aims to provide anti-angiogenic and immunomodulatory effects alongside direct cytotoxicity. Zoledronic acid is included to inhibit osteoclast activity and potentially exert direct anti-tumor effects in bone-involved malignancies.

Other names

sirolimus + CP + MT + ZAmetronomic cyclophosphamide and methotrexate combined with zoledronic acid and sirolimus