In the study, animals treated with pemetrexed alone showed 9.7% tumor growth inhibition. Animals treated with lucanthone alone showed 20% tumor growth inhibition. Animals treated with a combination of lucanthone and pemetrexed showed an approximately 45% tumor growth inhibition demonstrating that lucanthone is synergistic with pemetrexed.
Lucanthone is an orally available small molecule inhibitor of DNA repair (AP endonuclease). Since DNA damage that is caused by pemetrexed is repaired by Base Excision Repair (BER) and since lucanthone inhibits AP endonuclease, a key component of BER pathway, it is hypothesized that lucanthone will potentiate the activity of pemetrexed.
The company is expected to initiate shortly a Phase I dose-escalation study of lucanthone in patients with recurrent malignant gliomas receiving temozolomide.
Rajesh Shrotriya, chairman, president and CEO of Spectrum, said: “Based on preclinical data, we believe we may have expanded the potential use of lucanthone to the treatment of lung cancer.”