Phase i Study of Panobinostat (LBH589) and Letrozole in Postmenopausal Metastatic Breast Cancer Patients

Winston W. Tan, Jacob B. Allred, Alvaro Moreno-Aspitia, Donald W. Northfelt, James N. Ingle, Matthew P. Goetz, Edith A. Perez

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Introduction Histone deacetylase inhibitors have been found to restore sensitivity to the estrogen receptor in endocrine-resistant and triple-negative breast cancer cell lines. We decided to test panobinostat, a pan-histone deacetylase inhibitor, because of preclinical data, combined with letrozole in a phase I study. Patients and Methods We enrolled patients with metastatic breast cancer to determine the safety and tumor response using Response Evaluation Criteria In Solid Tumors. Dose level 1 was panobinostat 20 mg orally 3 times weekly with oral letrozole 2.5 mg daily. Dose level 2 was panobinostat 30 mg orally 3 times weekly, with the same dose of letrozole. Results A total of 12 patients (6 at each dose level) were enrolled, and 43 cycles of treatment were given. Of the 6 patients at dose level 1, 1 experienced dose-limiting toxicity (20-mg dose level; an increase in creatinine). At the 30-mg dose level, 3 of 6 patients experienced dose-limiting toxicity, 1 each of grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia, and grade 3 diarrhea. The maximum tolerated dose was 20 mg. Of the 12 patients, 2 experienced a partial response, and 5 had stable disease. The most common severe adverse event was thrombocytopenia, occurring in 4 of 12 patients. Conclusion The recommended phase II starting dose is panobinostat 20 mg orally 3 times weekly (eg, Monday, Wednesday, Friday) and oral letrozole 2.5 mg daily. This dose should be escalated to 30 mg orally 3 times weekly if no grade 3 toxicity has developed, because the partial responses occurred in patients receiving the 30-mg dose.

Original languageEnglish (US)
Pages (from-to)82-86
Number of pages5
JournalClinical breast cancer
Issue number2
StatePublished - Apr 1 2016


  • Aromatase refractory
  • Endocrine resistant breast cancer
  • Histone deacetylase inhibitors
  • Phase I study

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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