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

Clin Cancer Res. 1998 Jun;4(6):1567-71.


A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing 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 receive either oral pyridoxine or placebo daily during Doxil chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutaneous toxicity was determined by clinical and histological scoring. No difference was observed in remission rates (71.4 versus 75%) achieved between groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely abrogate PPES; however, it occurred later and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dose of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received 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 receiving pyridoxine, which was likely attributable to their ability to receive more Doxil without delay or discontinuation. We conclude that pyridoxine is effective in delaying the onset and severity of PPES in this canine model.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use
  • Dog Diseases / drug therapy*
  • Dog Diseases / mortality
  • Dog Diseases / pathology
  • Dogs
  • Double-Blind Method
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects*
  • Doxorubicin / therapeutic use
  • Drug Carriers
  • Female
  • Liposomes
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / veterinary*
  • Male
  • Neoplasm Staging
  • Pyridoxine / therapeutic use*
  • Skin / drug effects
  • Skin / pathology*
  • Survival Analysis
  • Time Factors


  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Liposomes
  • Doxorubicin
  • Pyridoxine