Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors

Abstract

This Phase I clinical trial has demonstrated that these 2-drug and 3-drug combinations are generally well tolerated and safely administered. The main DLTs in both regimens were hematologic, specifically thrombocytopenia. The 3-drug combination can be considered as a platform for future studies in specific tumor types.

Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

“…Therefore, elucidation of the mechanism of chemoresistance in PDAC patients may contribute to the development of novel therapeutic strategies for advanced PDAC. This study demonstrated that chronic gemcitabine exposure led to the isolation of DR cells that displayed higher resistance to gemcitabine, a prototype genotoxic drug that is a first-line treatment in human PDAC therapy [31]. These findings suggest that PDAC cells had strong capabilities to adapt to hostile factors, which led to the selection of DR subpopulations.…”

Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets

“…Several mTOR inhibitors, such as temsirolimus and everolimus, are available in the market and are US Food and Drug Administration-approved for several tumour types. A phase I clinical trial of everolimus in combination with gemcitabine and cisplatin for solid tumours, including cholangiocarcinoma, showed some promise 44. Another phase I clinical trial of MK-2066, oral pan-AKT inhibitor, also showed favourable outcome in a subset of patients with solid tumours 45.…”

“…Another phase I clinical trial of MK-2066, oral pan-AKT inhibitor, also showed favourable outcome in a subset of patients with solid tumours 45. In addition, various PI3K inhibitors such as GDC-0980 and BAY80-6946 are under investigation for clinical trials 44 46…”

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression

“…Cisplatin is a first line platinum-based chemotherapeutic agent, which exerts marked antitumor activity in a number of solid tumors (8)(9)(10)(11)(12). It is also one of the most commonly used agents for the treatment of ovarian cancer.…”