An open label phase II study of safety and clinical activity of naltrexone for treatment of hormone refractory metastatic breast cancer

Jayanthi Vijayakumar, Tufia Haddad, Kalpna Gupta, Janet Sauers, Douglas Yee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The opioid receptor (OR) antagonist naltrexone inhibits estrogen receptor-α (ER) function in model systems. The goal of this study was to determine the clinical activity of naltrexone in patients with ER-positive metastatic breast cancer. Patients with hormone receptor positive metastatic breast cancer were enrolled on a phase II study of naltrexone. An escalating dose scheme was used to reach the planned dose of 50 mg daily. The primary objective of the study was to evaluate response to therapy as measured by stabilization or reduction of the tumor Maximum Standardized Uptake Value (SUVmax) at 4 weeks by PET-CT scan. The secondary objectives included safety assessment and tumor SUVmax at 8 weeks. Out of 13 patients we enrolled, 8 patients had serial PET-CT scans that were evaluable for response. Of these 8 patients, 5 had stable or decreased SUVmax values at 4 weeks and 3 had clinical or imaging progression. Median time to progression was short at 7 weeks. Naltrexone was well tolerated. There were no discontinuations due to toxicity and no grade 3 or 4 toxicities were noted. Naltrexone showed modest activity in this short study suggesting the contribution of opioid receptors in ER-positive breast cancer. Our data do not support further development of naltrexone in hormone refractory breast cancer. It is possible that more potent peripherally acting OR antagonists may have a greater effect. ( Identifier: NCT00379197 September 21, 2006).

Original languageEnglish (US)
Pages (from-to)70-75
Number of pages6
JournalInvestigational New Drugs
Issue number1
StatePublished - Feb 2023

Bibliographical note

Funding Information:
This single center open label phase II study was conducted at the M Health Fairview Masonic Cancer Clinic. Informed consent was obtained prior to performance of any study related procedures or assessments. The study was reviewed and protocol approved by institutional review board. The study was funded by a supplement to the Masonic Cancer Center’s Cancer Center Support Grant (P30 CA 077598) and registered as clinical trials number NCT00379197. Naltrexone was purchased for use in this trial.

Funding Information:
This work was supported by a supplement to P30 CA 077598 Avon-NCI “Progress for Patients” award.

Publisher Copyright:
© 2022, The Author(s).


  • Breast cancer
  • Estrogen receptor
  • Mu-opioid receptor
  • Naltrexone
  • Positron emission tomography

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Journal Article
  • Research Support, N.I.H., Extramural


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