Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer.

ABSTRACT:

Objectives

Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open-label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage non-small cell lung cancer (NSCLC).

Materials and methods

This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV NSCLC or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions.

Results and concl

SUBMITTER: Garon EB 

PROVIDER: S-EPMC3939783 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature