For patients initially presenting with localized sarcoma the standard of care is surgery
followed by with radiation therapy (if feasible). Subsequent or adjuvant cytotoxic based
chemotherapy even for aggressive sarcoma histopathologies (as commonly done for colorectal
cancer or breast cancer) is controversial since over 20 individual adjuvant randomized
clinical trials have not been able to consistently demonstrate a statistically significant
improvement in overall survival. Maturation or differentiation therapy provides an
opportunity to fundamentally change the biology of the underlying cancer (and thus its
overall prognosis) by promoting cellular maturation within that cancer. A change from a
poorly 'differentiated/high grade' tumor to a well 'differentiated/low grade' tumor is
attainable and can change an individual's median time of survival from months to decades. The
investigators have significant preclinical data that differentiation therapy using a group of
drugs referred to as histone deacetylase inhibitors (such as Valproate, also a commonly used
and safe anti seizure medication) is feasible for sarcomas. This approach has not been
clinically addressed in solid tumors. Since adjuvant therapy is controversial for sarcomas,
and building on the investigators' preclinical data, adjuvant based differentiation therapy
using valproate would be predicted to be both safe and potentially extremely beneficial in
terms of a) increasing the time to disease recurrence, b) improving the histology upon
recurrence; and c) improving overall survival in patients with sarcomas.
Patients with high grade sarcomas will receive Valproate in the adjuvant setting daily and
clinically/radiologically followed until recurrence. Relapse free survival, time to local
failure, time to distant failure, overall survival, and comparative histopathology of primary
and recurrence will be assessed.