abstract: Phase I trial of ATRA-IV and depakote in patients with advanced solid tumor malignancies

Phase I trial of ATRA-IV and Depakote in patients with advanced solid tumor malignancies.
David KA, Mongan NP, Smith C, Gudas LJ, Nanus DM.
Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College - New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA.

Retinoic acid derivatives have shown their greatest benefit in acute promyelocytic leukemia, but have also demonstrated pre-clinical anti-cancer effects in some solid tumors. Histone deacetylase inhibitors, by upregulating gene expression, are able to limit cancer cell proliferation and induce apoptosis. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid has been previously studied in hematologic malignancies. We conducted a phase I two-step dose escalation trial of the liposomal ATRA analog ATRA-IV and divalproex sodium (Depakote((R))) in nine patients with advanced solid tumors refractory to prior therapy. Side effects attributed to therapy had a severity