Pharmacodynamic and Pharmacokinetic Properties of AFPep, a Novel Peptide for the Treatment of Breast Cancer

AFPep is a small synthetic cyclized peptide derived from alpha-fetoprotein that has been shown to have anti-estrogenic and anti-breast cancer activity. The purpose of this study was to establish blood levels of AFPep that are associated with biological activity. Blood levels of AFPep were measured by LC/MS/MS. Once daily treatment of mice with 4 mg/kg i.p. AFPep yielded a C_max of 7 µg/ml and was sufficient to inhibit estrogen-stimulated growth of mouse uterus and of human breast cancer xenografts even though the half-life of this drug was only 11 min in mice, suggesting that its biological effects last much longer than its chemical half-life. In dose de-escalation studies, blood levels of 100 ng/ml of AFPep were still found to be biologically active. AFPep was effective by parenteral routes and with dose escalation also by the oral route. Blood levels of AFPep that were biologically effective in mice were readily achieved in dogs through parenteral as well as oral routes with no apparent evidence of host toxicity. In conclusion, AFPep blood levels can be measured by LC/MS/MS with accuracy into the ng/ml range. Blood levels in the 100 ng/ml range are associated with efficacious biological activity. This drug shows great promise for the treatment as well as prevention of breast cancer.