Valproic Acid (Depakote ER) in Patients With Advanced Thyroid Cancer

A Phase II Trial of Valproic Acid (Depakote ER ®) in Patients With Advanced Thyroid Cancers of Follicular Origin, Who Are Thyroglobulin Positive/RAI Unresponsive

RATIONALE: Drugs such as valproic acid may make thyroid cancers more radioiodine sensitive, which will allow for detection of tumor and make further ablation treatment effective.

PURPOSE: This phase II trial is studying how well valproic acid works in treating patients with thyroid cancers that do not respond well to other treatments.

INCLUSION CRITERIA:

DISEASE CHARACTERISTICS

• Diagnosis of advanced/poorly differentiated thyroid cancer of follicular cell origin that is radioiodine-unresponsive
• Cumulative dose of radioiodine < 800 mCi
• No radioiodine uptake on whole body scan within 18 months of enrollment
• Inoperable extensive locoregional tumor mass and/or metastatic spread
• Failed conventional therapy that included total thyroidectomy AND radioactive iodine I 131 ablation
• Elevated thyroglobulin level (>2ng/ml on thyroid hormone, >10ng/ml off thyroid hormone)or Tg-antibody positive

PATIENT CHARACTERISTICS

-18 years or older

Entry lab results:

• Hemoglobin > 8.0 gm/dl
• Absolute Neutrophil Count > 750 cells/mm3
• Platelet count > 75000/mm3
• BUN < 1.5 times upper limit of normal (ULN)
• Creatinine < 1.5 times ULN
• Total protein > 6.4
• Total bilirubin should be < 1.5 times ULN.
• AST (SGOT), ALT (SGPT), ALKP and amylase < 1.5 times ULN
• Amylase < 1.5 times ULN
• Albumin > 2.5
• Ammonia < 1.5 times ULN

EXCLUSION CRITERIA:

• Not pregnant
• No nursing within the past 3 months
• No allergy to valproic acid
• No coexisting malignancy other than basal cell carcinoma
• No hepatic disease or significant dysfunction
• Karnofsky score > 80
• No pancreatitis
• No kidney dysfunction
• Fertile patients must use effective contraception