Treatment with panobinostat and epirubicin is well tolerated and may be active in patients with sarcoma who are refractory to anthracycline-based therapy, a study published in the journal Annals of Oncology has shown.1
Treatment options are limited for patients with sarcoma. Because inhibition of histone deacetylase appears to improve the efficacy of topoisomerase 2 inhibitors, researchers sought to evaluate panobinostat combined with epirubicin in patients with refractory sarcoma.
For the phase 1 study, researchers enrolled 40 patients with advanced solid tumors. Participants received panobinostat 20 to 60 mg orally on days 1, 3, and 5, followed by epirubicin 75 mg/m2 intravenously on day 5 in 3-week cycles. Researchers also conducted a dose expansion at the maximum tolerated dose of panobinostat in the 20 patients with sarcoma.
Results showed that thrombocytopenia, febrile neutropenia, and fatigue were dose-limiting toxicities at 60 mg of panobinostat, making 50 mg the maximum tolerated dose.
Researchers found that 4 of the 37 evaluable patients achieved a response, all of which were after progression on prior topoisomerase 2 inhibitors, such as doxorubicin and epirubicin.
Of the 20 patients with refractory sarcoma, 1 achieved a partial response and 11 had stable disease. Median overall survival for these patients was 8.3 months.
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“Panobinostat and epirubicin treatment…may reverse anthracycline resistance,” the authors wrote.
The study also demonstrated that increased mononucleocyte histone acetylation in the peripheral blood and reduced neutrophil count on day 5 correlated with treatment benefit, suggesting a role as predictive biomarkers.
- Thomas S, Aggarwal R, Jahan T, et al. A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma [published online ahead of print February 21, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw044.