application): Paclitaxel (Taxol) has shown significant activity in human cancers. However, clinical utility of Paclitaxel is limited by its insolubility in water and toxic side effects. We developed a water-soluble poly (L-glutamic acid)-Paclitaxel conjugate (PG-TXL) that has shown striking anti-tumor effects yet has low toxicity. A single intravenous injection of PG-TXL at its maximum tolerated dose resulted in complete disappearance of well-established breast and ovarian tumors in vivo. Based on its outstanding anti-tumor efficacy, PG-TXL is considered a promising anticancer agent for future clinical trials. The objective of the proposed studies is to investigate in detail the pre-clinical anti-tumor efficacy and relevant pharmacology/toxicology of PG-TXL and to address those aspects which will most likely influence the therapeutic efficacy and safety of PG-TXL in subsequent Phase I/II clinical trials.
The specific aims are: 1. To define the dose-time sequence which would maximize the anti-tumor effects of PG-TXL. 2. To determine the pre-clinical toxicity of PG-TXL and define the starting dose for a clinical trial for breast and ovarian cancer patients. 3. To develop an analytical assay for determination of the time-dependent concentration changes of PG-TXL. The applicant's goal is expressed in the following sentence: """"""""It is expected that PG-TXL will be less toxic and more effective than Taxol and that commercialization of PG-TXL in cancer patients will have significant impact on the management and treatment of breast cancer and ovarian cancer.""""""""
As a anti cancer agent.
