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

Clinical Breast Cancer
Winston W TanEdith A Perez

Abstract

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. 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. 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. The reco...Continue Reading

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Citations

Sep 28, 2017·Expert Opinion on Investigational Drugs·Palma FedeleSaverio Cinieri
May 18, 2019·Molecular Oncology·Aurélien LinaresVincent Cavaillès
Oct 11, 2019·Journal of breast cancer·Maryam NakhjavaniAmanda R Townsend
Nov 18, 2017·BMC Biology·Sara Sannino, Jeffrey L Brodsky
Oct 11, 2019·Cells·Mohammad Mijanur RahmanTrygve O Tollefsbol
Jul 2, 2017·Clinical Pharmacokinetics·Mathilde Van VeggelPaul Hamberg
Jun 21, 2018·Molecular Cancer Research : MCR·Deborah MolehinKevin Pruitt
Aug 14, 2019·Bioorganic Chemistry·Meiling HuangRui Ling
Mar 7, 2021·International Journal of Molecular Sciences·Jinsha LiuSepideh Afshar
May 17, 2021·Molecular and Cellular Endocrinology·Deborah MolehinKevin Pruitt

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