PB, an aromatic fatty acid, demonstrates potent differentiating effects on multiple tumor cell lines. PB has pleiotropic molecular effects at concentrations of 0.5 -2.5 mM in vitro. This study of thrice daily oral PB is ongoing with 22 patients enrolled (12 advanced prostate cancer (CA), 4 renal cell CA, 2 breast CA, 2 thyroid CA, 1 colon CA, 1 bladder). Dose escalation is complete through 45g/day. Two dose-limiting toxicities were noted at 45 g/day, so patient accrual continues at the 36g/day to further evaluate toxicity and compliance. Compliance has been excellent, despite the oral formulation, with patients ingesting 12 -24 500 mg tablets 3X a day. Pharmacokinetics were obtained after equivalent oral and IV doses prior to chronic dosing. AUCoral /AUCiv for PAG equals the fraction of PB absorbed from the GI tract. The oral bioavailability of PB is less than the fraction of PB absorbed from the GI tract because of hepatic first pass metabolism. At higher doses, PB concentrations remain above 0.5 mmol/L (in vitro bioactive threshold) nearly 4 hours. Toxicity has been mild with fatigue and lethargy cited most frequently. No measurable responses have been noted, yet 6 patients have had stable disease for 6 months. PSA has declined by >50% in 1 patient at 36g/day, and 4 patients have had PSA stabilization over 2-6 months. Overall, oral PB is well-tolerated, with in vitro bioactive concentrations being consistently achieved in vivo.
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