EFFICACY OF PYRIDOXINE TO AMELIORATE THE CUTANEOUS TOXICITY ASSOCIATED WITH DOXORUBICIN CONTAINING PEGYLATED (STEALTH) LIPOSOMES - A RANDOMIZED, DOUBLE-BLIND CLINICAL-TRIAL USING A CANINE MODEL

A cutaneous reaction termed palmar-plantar erythro-dysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin co ntaining pegylated (Stealth) liposome, The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non -Hodgkin's lymphoma were randomized in a double-blind fashion to recei ve either oral pyridoxine or placebo daily during Doxil chemotherapy ( 1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutane ous toxicity was determined by clinical and histological scoring. No d ifference was observed in remission rates (71.4 versus 75%) achieved b etween groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) g reater in placebo group dogs than in pyridoxine group dogs (P = 0.032) , Pyridoxine did not completely abrogate PPES; however, it occurred la ter and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulat ive dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dos e of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs receive d a median of 2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028), A trend (P = 0. 084) toward prolongation of remission length was observed in dogs rece iving pyridoxine, which was likely attributable to their ability to re ceive more Doxil without delay or discontinuation. We conclude that py ridoxine is effective in delaying the onset and severity of PPES in th is canine model.