It is estimated that nearly 23,400 new cases of primary malignant brain and central nervous system (CNS) tumors will be diagnosed in the United States in 2014; of those, approximately 2,240 will be diagnosed in children ages 0 to 14 years and 540 will be diagnosed in adolescents ages 15 to 19 years. Overall mortality rates have not changed significantly in the past decade. Both incidence and mortality rates are higher for whites than for people of other racial/ethnic groups. In all racial/ethnic groups, men have higher incidence and mortality rates than women. Brain tumors are the leading cause of death from solid tumor cancers in children. Brain and CNS tumors make up approximately 21 percent of all childhood cancers. The incidence rate of brain and CNS cancers in children has been relatively stable since the mid-1980s, but the death rate has dropped over this period.
The causes of most brain and CNS cancers are not known. However, factors that may increase the risk of developing certain types of brain tumors include exposure to radiation, exposure to vinyl chloride, and having certain genetic syndromes. There are no screening tests for brain and CNS cancers. Standard treatments for adult brain cancer include watchful waiting, surgery, radiation therapy, chemotherapy, and targeted therapy. Newer treatments for adult brain cancer, such as biological therapy and proton beam radiation therapy are being studied in clinical trials. Assuming that incidence and survival rates follow recent trends, it is estimated that $4.9 billion will be spent on brain cancer care in the United States in 2014.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. To treat brain tumors, a wafer that dissolves may be used to deliver an anticancer drug directly to the brain tumor site after the tumor has been removed by surgery. The way the chemotherapy is given depends on the type and grade of tumor and where it is in the brain.
Anticancer drugs given by mouth or vein to treat brain and spinal cord tumors cannot cross the blood-brain barrier and enter the fluid that surrounds the brain and spinal cord. Instead, an anticancer drug is injected into the fluid-filled space to kill cancer cells there. This is called intrathecal chemotherapy.
Local, sustained drug release using biodegradable polyanhydride poly-(1,3 bis[p-carboxyphenoxy] propane-co-sebacic acid, or p[CPP:SA, 20:80], improves the anti-glioma efficacy of some chemotherapeutic agents for treatment of brain tumors. P[CPP:SA, 20:80] is an FDA-approved method of local drug delivery that has been shown to be biocompatible in the brain with no evidence of systemic or local toxicity and is currently clinically used for the local delivery of BCNU (GLIADEL®). Despite vast improvements in overall survival rates in systemic cancers, primary brain malignancies still have some of the worst 5-year survival rates among all human cancers (Macmillan Cancer Support. Living after diagnosis—median cancer survival times: An analysis of London School of Hygiene and Tropical Medicine, 2011).
There remains a need for efficacious treatments to extend the median survival of subjects with brain tumor or other solid tumors.
Therefore, it is an object of the present invention to provide local delivery forms of chemotherapeutics for treatment, prophylaxis, or management of proliferative diseases.
It is another object of the present invention to provide methods of making the local delivery formulations.
It is yet another object of the present invention to provide methods of using the local delivery forms of local delivery formulations.
USPTO Backgrounds
USPTO Backgrounds