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KX-ORAX-007 A Clinical study to determine the pharmacokinetics of Oraxol in breast cancer patients

Background

Breast cancer is the most common invasive cancer in women. It affects about 12% of women worldwide. Risk factor for breast cancer include drinking alcohol, obesity, older age, family history of breast cancer having children late or not etc. About 5-10% of breast cancer are cause by inherited. Women whose BRCA1 and BRCA2 gene mutation have higher risk of breast cancer. Breast cancer mostly develops from the lining of milk ducts and the lobules, 90% of breast cancer are adenocarcinomas, which arise from glandular tissue. The earliest sign of breast cancer is an abnormality that shows up on a mammogram before it can be felt by the woman.

If untreated, the cancer can spread to other areas of the body through lymph or blood. The diagnosis of breast cancer is confirmed by taking a biopsy of the concerning lump. Once confirmed of diagnosis, further tests are done to determine if the cancer has spread beyond the breast.

Unmet medical needs

Currently, several therapies are used for breast cancer, including surgery, radiation therapy, target drug, hormone therapy and chemotherapy. Chemotherapy is a treatment option for most type of breast cancer. The most common chemotherapy is intravenous (IV) paclitaxel with 80mg/m2 weekly. Mechanism of action is through tubulin-binding, causing stabilization of the microtubule assembly, ultimately leading to mitotic arrest and apoptosis. IV paclitaxel could reduce cancer-related symptom and prolong survival. Weekly infusions of paclitaxel have gained wide popularity because of the favorable toxicity profile allowing dose intensification. However, IV administration of paclitaxel is inconvenient to patients and associated with significant and unpredictable side effects. Hospitalization, medical and nursing assistance and infusion equipment are required for IV administration of paclitaxel. Implement of artificial blood vessel are also uncomfortable.

Oral administration of paclitaxel is convenient and practical for patients, oral administration enables the development of chronic treatment schedules, resulting in sustained plasma concentrations above a pharmacologically. Effective blood concentrations of paclitaxel and duration can predict clinical outcomes. Unfortunately, paclitaxel has very low level of oral bioavailability, at less than 10%. This poor bioavailability level results from limited aqueous solubility and dissolution affinity for the intestinal and liver cytochrome P450 metabolic enzymes and the multidrug efflux pump p-glycoprotein, which is present abundantly in the gastrointestinal tract.

Incentive of the trial

Oraxol is an oral dosage form of the chemotherapeutic agent paclitaxel administered with a novel p-glycoprotein inhibitor, to enhance the oral absorption of paclitaxel in cancer patients. Previous study show that the dose of this study is likely to produce a paclitaxel exposure similar to that of 80mg/m2 IV paclitaxel per week. Effective blood concentrations of paclitaxel and duration can predict clinical outcomes. The primary objective of the study is to investigate the PK of orally administered paclitaxel in breast cancer patients.