Randomized, Controlled Phase II Study of Valproic Acid in Patients With Non-metastatic Biochemical Progression of Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed prostate cancer

- Asymptomatic, non-metastatic disease

- Biochemical progression after definitive local therapy (radical prostatectomy)

- Most recent prostate-specific antigen (PSA) level ≥ 1.0 ng/mL AND rising over
the prior value

- No clinical or radiological evidence of local progression

- PSA doubling time (DT) < 10 months after local therapy (in patients who have not
received prior hormone therapy)

- At least three PSA values (each at least 4 weeks apart) are required to
calculate the PSA-DT

- No clinical or radiological evidence of metastatic disease, including bone metastasis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 3 months

- Total bilirubin normal

- AST/ALT < 2.5 times upper limit of normal

- Creatinine ≤ 2.5 mg/dL

- Platelet count > 125,000/mm^3

- PT and aPTT ≤ 1.3 times above the standard reference

- Albumin ≥ 3.5 g/dL

- Geographically accessible and willing to participate in all stages of study treatment

- No active second malignancy

- No known HIV positivity

- No active, uncontrolled infection (e.g., hepatitis A, B, or C infection)

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to valproic acid

- No debilitating medical or psychiatric illness that would preclude giving informed
consent or receiving optimal study treatment and follow-up

- No history of hepatic disease or significant hepatic dysfunction

- No history of pancreatitis

- No history of seizure disorder or clinically treated bipolar disorder

PRIOR CONCURRENT THERAPY:

- More than 6 months since prior hormone therapy

- No prior valproic acid

- At least 2 weeks since prior drugs specifically known to interact with valproic acid
including, but are not limited to, aspirin, felbamate, rifampin,
amitriptyline/nortriptyline, carbamazepine, clonazepam, diazepam, ethosuximide,
lamotrigine, phenobarbital, primidone, phenytoin, tolbutamide, warfarin, or
zidovudine

- No concurrent systemic chemotherapy for prostate cancer

- No other concurrent investigational drugs