OP26 – Combination Therapy of Oral Valproic Acid, Cisplatin, Doxorubicin, Surgery, and Radiation for Anaplastic Thyroid Cancer

      Noguchi, Hitoshi1; Uchino, Shinya1; Murakami, Tsukasa1; Noguchi, Shiro1 1 Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, Japan   Background: We have been using oral valproic acid (VA) as an HDAC inhibitor in combination with cisplatin (CDDP), doxorubicin (DXR), surgery and radiation for anaplastic thyroid cancer (ATC) since 2006. Methods: On a trial and error bases, we started with 100mg/m2 of CDDP and 50mg/m2 of DXR with 1200mg of VA at 4 week intervals for 3 courses before surgery and 1 course after. We eventually settled on 75mg/m2 of CDDP and 37.5mg/m2 with 1200mg of VA for 2 courses before surgery and 1 course after. Results: Out of 16 cases, 4 were in complete remission more than 12 months after treatment. Median survival of 16 cases were 222 days, non-survivors 187 days. Discussion: The results were equivalent to previous reports treated with CDDP and DXR without VA but with more than twice the chemotherapy agents. The addition of VA may have decreased the amount of chemo by half to two thirds. Conclusion: VA combination therapy merits further study.   References:
    1. De Crevoisier R et al. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1137-43.
    2. Catalano MG et al. Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells. J Endocrinol. 2006 Nov;191(2):465-72.


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