Purpose: This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing. Experimental Design: Sixty-seven patients with advanced solid tu...

Vismodegib (Erivedge, GDC-0449) is a first-in-class, orally administered small-molecule Hedgehog pathway inhibitor that is approved for the treatment of advanced basal cell carcinoma. Previously, we reported results from preclinical and clinical radiolabeled mass balance studies in which we determined that metabolism is the main route of vismodegib elimination. The metabolites of vismodegib are...

PURPOSE This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing. EXPERIMENTAL DESIGN Sixty-seven patients with advanced solid tu...

The hedgehog (Hh) signaling pathway is aberrantly activated in a majority of basal cell carcinomas (BCC). Vismodegib and sonidegib are targeted inhibitors of Smoothened (SMO). Both drugs are approved for use in locally advanced BCC (laBCC), with vismodegib also approved for metastatic BCC (mBCC).

BACKGROUND Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib. OBJECTIVE We sought to assess efficacy and safety of vismodegib, while providing e...

IMPORTANCE Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. OBSERVATIONS The first case is that of a patient with locally advanced ba...

PURPOSE The Hedgehog signaling pathway is a key regulator of cell growth and differentiation during development. Whereas the Hedgehog pathway is inactive in most normal adult tissues, Hedgehog pathway reactivation has been implicated in the pathogenesis of several neoplasms including BCR-ABL1-positive leukemia. The clear link between the Hedgehog pathway and BCR-ABL1-positive leukemia led to an...

PURPOSE Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advanced basal cell carcinoma (BCC). We conducted a pharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure. EXPERIMENTAL DESIGN In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a ...

BACKGROUND On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. ME...

Purpose: Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advancedbasal cell carcinoma (BCC).We conducted apharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure. Experimental Design: In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a low...