Case Number 113035 - Letrozole Treatment of Primary Brain Tumors

Contact: Jill Uhl
Phone: 513-558-5621

Description:  Dr. Pankaj Desai has discovered that aromatase inhibitors usually used in the treatment of estrogen receptor (ER+) positive breast cancer surprisingly exhibited potent activity against brain tumors in various preclinical models.

Treatment of primary and metastatic brain tumors remains one of the most formidable challenges in oncology. According to the Central Brain Tumor Registry of the United States close to 70,000 new cases of primary brain tumors were diagnosed in 2013 consisting of about 25,000 malignant and 45,000 non-malignant brain tumors. As many as 175,000 cases of secondary brain tumors are diagnosed annually in the US. Currently the overall prognosis for brain tumors is dismally poor. The average survival rate for all malignant brain tumor patients is 33.8% and an estimated 14,000 people in the USA will have died from brain cancer in 2013. Neurosurgical techniques and radiation therapy of brain tumors is often complicated by the deep tissue location of many tumors or invasion of critical function sites. Chemotherapy treatment of primary and metastatic brain tumors is impeded by the lack of well-identified targets as well as by the difficulty of finding drugs that pass through the blood-brain and blood-tumor barriers. Patients with primary malignant brain tumors often experience significant neurological disability, impaired quality of life and reduced survival.

Dr. Desai's laboratory used cutting edge pharmacokinetic and pharmacodynamics assessment tools to discover that letrozole selectively accumulates in brain tumor tissue 2-to-3 fold higher relative to normal brain tissue and causes marked reduction in the size of C6 glioma orthotopically implanted in rats. Via PET/CT scanning of tumors in experimentally implanted rats it was shown that letrozole treatment resulted in a significant reduction of 75-90% of active tumor volume after only 8-10 days of treatment with this aromatase inhibitor.

In summary, letrozole which is the most efficacious and safe aromatase inhibitor in the treatment of ER+ breast tumors in post-menopausal women, and is FDA approved, has similar promise for the treatment of human brain tumors. Human clinical trial studies are in the planning stage currently.

Patent application filed (US 14/096,536 filed 12-4-13 with priority claim to US 61/732,976 filed 12-4-12) titled "Methods of Treating Primary Brain Tumors by Administering Letrozole"