Phase I Trial of Everolimus Plus Sorafenib for Patients with Advanced Renal Cell Cancer

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial

“…Notwithstanding, our younger cohort tolerated this combination slightly better than what is reported in previous experiences [23][24][25] . In synthesis, toxicity was relevant, but manageable in most cases.…”

“…In phase I/II trials this combination has been extensively studied in renal and hepatic cancers at several different doses [23][24][25] showing that it is feasible. Given our former experience with sorafenib at full dose, we regarded sorafenib and everolimus at the daily dose of 800 and 5 mg, respectively, as the most appropriate dose to be explored in HG-OS.…”

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation

“…Preclinical studies have shown synergistic effects in mice with a combination of everolimus (mTOR inhibitor) and sorafenib (30). Phase I studies in renal cell and hepatocellular cancer have shown that the combination of everolimus and sorafenib was active and tolerable (31)(32)(33). Other phase I studies with everolimus and sorafenib are ongoing, among others in patients with lung cancer (34).…”

Phase I study of the combination of temsirolimus and pazopanib in advanced solid tumors

“…Additionally, several trials of the oral mTOR inhibitor everolimus in combination with the VEGFR inhibitors sorafenib and sunitinib have recently been reported [15–18]. In one study, the combination of full dose sorafenib was tolerable with half doses of everolimus, although DLT was observed in 25% of patients treated at these doses and full dose everolimus with half dose sorafenib was not tolerated [16].…”

“…Due to chronic toxicities seen at lower doses over time, no attempt was made to dose both drugs at the full monotherapy doses in this trial. In contrast, Amato et al found that full doses of everolimus and sorafenib could be given without DLT, at least in their population of predominantly Zubrod 0 performance status patients with RCC [15]. Significant modification of both the dose and schedule of everolimus and sunitinib were required to find a tolerable dose of this combination, and the dose had to be reduced further if patients were to be treated chronically [17].…”