The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma

PLoS One. 2018 Oct 4;13(10):e0204830. doi: 10.1371/journal.pone.0204830. eCollection 2018.


The objective of this study was to evaluate the effect of low-dose naltrexone (LDN) as a carboplatin chemotherapy-associated drug in female dogs with mammary carcinoma in benign mixed tumors (MC-BMT) after mastectomy and to assess its association with quality of life and survival rates. Sixty female dogs were included in this study, all of which had histopathological diagnosis of MC-BMT and were divided into three groups: G1 (control), consisting of animals submitted only to mastectomy with or without regional metastasis; G2, composed of treated animals that did not present with metastasis; and G3, treated dogs that presented with metastasis. G2 and G3 were also subdivided according to the treatment administered: chemotherapy alone (MC-BMT(-) C/MC-BMT(+) C) or LDN and chemotherapy (MC-BMT(-) C+LDN/MC-BMT(+) C+LDN). All animals were subjected to clinical evaluation, mastectomy, peripheral blood lymphocyte immunophenotyping, beta-endorphin and met-enkephalin quantification, and evaluation of survival rates and quality of life scores. The results showed higher serum concentrations of beta-endorphin and met-enkephalin, fewer chemotherapy-related side effects, and better quality of life and survival rates in the LDN-treated groups than in LDN-untreated groups (P < 0.05). Evaluation of clinical and pathological parameters indicated a significant association between the use of LDN and both prolonged survival and enhanced quality of life. These results indicate that LDN is a viable chemotherapy-associated treatment in female dogs with MC-BMT, maintaining their quality of life and prolonging survival rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboplatin / administration & dosage*
  • Carboplatin / pharmacology*
  • Dogs
  • Drug Synergism
  • Enkephalin, Methionine / metabolism
  • Female
  • Immunophenotyping
  • Lymphocytes / metabolism*
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / immunology
  • Mammary Neoplasms, Animal / surgery
  • Mastectomy / veterinary
  • Naltrexone / administration & dosage*
  • Naltrexone / pharmacology
  • Neoplasm Metastasis
  • Quality of Life
  • Survival Analysis
  • Treatment Outcome
  • beta-Endorphin / metabolism


  • Enkephalin, Methionine
  • Naltrexone
  • beta-Endorphin
  • Carboplatin

Grant support

This work was supported by the Foundation for Research Support of Bahia State (FAPESB - grant 3538/2013). The authors are profoundly grateful to the Program of Postgraduate Studies in Tropical Animal Science (PPgCAT). Marília Carneiro Machado is a Master fellow from the Coordination on Higher Education Personnel Improvement (CAPES). Alessandra Estrela-Lima and Olindo Assis Martins-Filho are research fellows from National Council for Scientific and Technological Development (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.