Novel phase I study combining G1 phase, S phase, and G2/M phase cell cycle inhibitors in patients with advanced malignancies.

ABSTRACT:

Purpose

Cancer is a manifestation of aberrant cellular proliferation, and the cell cycle is one of the most successfully drugged targets in oncology. No prior study has been reported that simultaneously targets the 3 principal cell cycle phases populated by proliferating cells--G1, S, and G2/M.

Methods

Temsirolimus (G1 inhibitor), topotecan (S inhibitor), and bortezomib (G2/M inhibitor) were administered in combination to patients with advanced malignancies using a 3+3 dose escalation schedule to assess the safety and establish the maximum tolerated dose (primary endpoints) of this cell cycle targeting approach. An in silico pharmacodynamic model using established effects of each of these agents on the cell cycle was used to validate the regimen and to guide the dosing regim

SUBMITTER: Jain RK 

PROVIDER: S-EPMC4825574 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature