A small subgroup of heavily pre-treated patients with soft tissue sarcoma may benefit from treatment with the histone deacetylase inhibitor (HDAC) vorinostat, a study published in the European Journal of Cancer has shown.1

Preclinical trials have demonstrated potential activity of vorinostat in soft tissue sarcoma; researchers therefore conducted this multicenter, open-label, phase 2 trial, for which 40 patients with locally advanced or metastatic soft tissue sarcoma who failed first-line anthracycline-based chemotherapy were enrolled. Of those, 20%, 25%, and 55% had received 1, 2, and 3 or more prior lines of therapy, respectively.

All participants received vorinostat 400 mg orally daily for 28 days of each 5-week cycles. Restaging of disease was performed every 3 cycles or at the time of clinical progression.

The best response after 3 cycles of vorinostat therapy was stable disease, which was observed in 23% of patients. Median progression-free survival and overall survival were 3.2 months and 12.3 months, respectively. Six patients demonstrated long-lasting disease stabilization for up to 10 cycles, though analyses were unable to identify baseline predictive markers in this small subgroup.

RELATED: Droplet Digital PCR Promising for Detecting Recurrent Ewing Sarcoma

Some grade 3 or higher toxicities were observed: 15% experienced hematologic toxicity, 13% had gastrointestinal disorders, 10% reported fatigue, 10% reported musculoskeletal pain, and 5% had pneumonia.

Further studies are warranted to identify predictive markers for treatment response to vorinostat, and vorinostat should be evaluated in combination with other agents in this difficult-to-treat patient population.                   

Reference

  1. Schmitt T, Mayer-Steinacker R, Mayer F, et al. Vorinostat in refractory soft tissue sarcomas – Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO). Eur J Cancer. 2016. [Epub ahead of print]