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

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. (ClinicalTrials.gov Identifier: NCT00379197 September 21, 2006).