Study results showed that menadione was well tolerated at all doses tested. The open-label, modified dose-escalation study assessed the bioavailability, safety and tolerability of three concentrations (0.05%, 0.1% and 0.2%) of menadione and placebo administered to 12 healthy subjects with intact skin.
Menadione or placebo was applied on the face, neck, upper chest and upper arms for 3.5 days every 7 days over a 28 day period. The study included skin biopsy specimens for analysis, patient tolerability questionnaires, and full pharmacokinetic sampling on all of the subjects at the various lotion strengths.
Results from past preclinical studies demonstrated that menadione does not affect the anti-tumor effect of erlotinib (Tarceva), an approved EGFR inhibitor. Other preclinical data showed menadione’s ability to restore kinase activity in the presence of specific kinase inhibitors.
A Phase I study in patients receiving EGFR inhibitors for anti-cancer therapy in both rash emergent and rash pre-emergent settings is ongoing, and the company expects to initiate a randomized Phase II trial during the first half of 2009.
Steven Deitcher, president and CEO of Hana Biosciences, said: We are encouraged by these study results that show study subjects experienced no appreciable systemic absorption of menadione at any concentration, which supports previously reported preclinical data that showed menadione does not interfere with the anti-cancer activity of EGFR inhibitors.
We are very excited about the potential for this promising novel agent and are convinced that successful prevention and treatment of this skin toxicity is needed to maintain compliance of the anti-cancer therapy.