Panobinostat Plus Epirubicin May Be Active in Refractory Sarcoma

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.

“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.

Reference

1. 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.