Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib.

Background: Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events.

Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma.

Purpose: Validated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy.

Experimental Design: In SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis.

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours.

Aim: The safety, pharmacokinetics and efficacy of sorafenib plus docetaxel in patients with advanced refractory cancer were investigated in a phase I, dose-escalation trial.

Methods: Twenty-seven patients in four cohorts received docetaxel on day 1 (cohorts 1 and 4: 75 mg/m2; cohorts 2 and 3: 100 mg/m2) plus sorafenib on days 2-19 (cohorts 1 and 2: 200 mg twice-daily (bid); cohorts 3 and 4: 400 mg bid) in 21-day cycles.

Results: Most common adverse events (AEs) (grade 3-5) included neutropenia (89%), leucopaenia (81%), hand-foot skin reaction (30%) and fatigue (30%).

Safety and Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma (HCC) and Child-Pugh A versus B Cirrhosis.

Background: We performed a retrospective analysis of data from a phase II study evaluating sorafenib in patients with advanced hepatocellular carcinoma (HCC) to assess differences in safety and efficacy based on Child-Pugh (CP) status (A/B).

Methods: Patients received sorafenib 400 mg PO bid. We analyzed safety, pharmacokinetic (PK), and efficacy data in the two CP groups.

Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study.

Background: In vitro data indicate that the sorafenib is a moderate inhibitor of cytochrome P450 (CYP) enzymes, including CYP3A4, CYP2C19, and CYP2D6. This phase I/II study in patients with advanced melanoma evaluated the potential effect of sorafenib on the pharmacokinetics of midazolam, omeprazole, and dextromethorphan, specific substrates of CYP3A4, CYP2C19, and CYP2D6, respectively.

Methods: Twenty-one patients received sorafenib 400 mg twice daily for 28 consecutive days.