Combination Therapy for Anaplastic Carcinoma of the Thyroid with Valproic Acid, Chemotherapy, and Surgery

  • Treatment for the anaplastic carcinoma of the thyroid has seen substantial advances with the introduction of tyrosine kinase inhibitors. However, although these drugs have shown amazing efficacy in the suppression of tumor size and extension of patient survival, there have been few incidences of disease free, treatment free remission. Combination therapy of surgery, chemotherapy, and radiation remains the best hope for complete remission. Starting in 2006, we have been adding oral valproic acid to a regimen of cisplatin (CDDP) and doxorubicin (DXR) with surgery. So far 6 out of 20 patients have survived disease free, treatment free, 5 of which still survive, 1 has died of unrelated causes after 13 years of remission. The remission rate of Stage IVa, with tumors confined to the thyroid and no metastasis, has been 100%. Our current regimen is 1200mg/day of oral valproic acid coupled with 37.5mg/m2 of DXR and 75mg/m2 of CDDP at four week intervals for 2 courses before surgery and an additional 1 course after surgery, with optional radiation where possible. The total amount of cytotoxic agents used is substantially smaller than with previous treatments. The treatment has been relatively well tolerated with no unexpected side effects. We hope to advance to a multicenter clinical trial in the near future.

 

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