Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer

J Clin Oncol. 2003 Mar 15;21(6):999-1006. doi: 10.1200/JCO.2003.05.068.


Purpose: Bexarotene is a retinoid X receptor-selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer.

Patients and methods: The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m(2)/d.

Results: One hundred forty-eight patients were randomized; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m(2)/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis.

Conclusion: The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bexarotene
  • Breast Neoplasms / blood
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Estrogen Receptor Modulators / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / adverse effects
  • Tetrahydronaphthalenes / therapeutic use*
  • Thyroid Hormones / administration & dosage
  • Thyroid Hormones / blood
  • Toremifene / administration & dosage
  • Treatment Outcome


  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tetrahydronaphthalenes
  • Thyroid Hormones
  • Tamoxifen
  • Toremifene
  • Bexarotene