A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma.

ABSTRACT:

Lessons learned

This study is a rare example of effective doses of both targeted agents being both administered and tolerated.This combination should not be used in melanoma.

Background

Sorafenib and bortezomib affect BCL family member expression. We previously demonstrated that bortezomib augmented sorafenib-mediated cytotoxicity in melanoma cell lines in vitro. We aimed to combine sorafenib 400 mg b.i.d. with increasing doses of weekly bortezomib.

Methods

Patients with metastatic melanoma were enrolled in dose-escalation cohorts to determine the maximum tolerated dose (MTD) of sorafenib (twice daily) in combination with bortezomib (weekly for 3 of 4 weeks). The MTD was defined as the highest dose level at which less than 33% of patients exhibited a dose-limiting tox

SUBMITTER: Sullivan RJ 

PROVIDER: S-EPMC4571786 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature