Phenylbutyrate is a prodrug of phenylacetate, an aromatic fatty acid. Patients are prescribed phenylbutyrate off-label to treat cancer. Sodium phenylbutyrate is classified by the FDA as an orphan drug for the treatment of urea cycle disorders. Phenylbutyrate and its metabolites have also been shown to increase fetal hemoglobin production in patients with thalassemia (1) and sickle cell disease (2).
Several phase I trials are underway to evaluate phenylbutyrate for leukemias, lymphomas, and refractory solid tumors. Published phase I studies indicate low toxicity and possible activity in these cancers. A number of patients experienced disease stabilization in these trials, although disease regression was not observed (3) (4) (5) (16). Although studies point to a potential role for phenylbutyrate in treating refractory cancers, additional clinical research is required.
Multiple dose escalation trials have been performed in patients with solid tumors (3) (4) (5), Huntington's disease (6), and Amyotrophic lateral sclerosis (7); however, the optimal dose has yet to be defined. Oral doses up to 36 grams per day have been used with minimal toxicity (4).
Reported adverse events include fatigue, dyspepsia, nausea, vomiting (4), body odor, anorexia, menstrual cycle irregularities, hypocalcemia, edema, skin rash, liver toxicity, and renal tubular acidosis. Each 500 mg tablet contains approximately 62 mg of sodium (8).