TPI 287 has emerged as a Tapestry's third generation taxane, which demonstrated the ability to inhibit tumour cell growth in a number of in vitro cell lines and has shown inhibition of human tumours in certain animal xenograft models when tested against standard comparative agents.
The in vitro activity was seen across multiple cell lines including cell lines known to be sensitive to taxanes and cell lines known to be resistant to taxanes.
In in vivo testing TPI 287 demonstrated reduction in the rate of tumour growth in both taxane resistant and taxane sensitive breast cancer xenografts.
Taxane sensitive cell lines in which TPI 287 shows activity include cell lines derived from breast cancer, uterine cancer and non-small cell lung cancer.
Taxane resistant cell lines in which TPI 287 shows activity include lines derived from breast cancer, colon cancer, prostate cancer and pancreatic cancer.
TPI 287 is currently in two Phase I studies in the United States and overseas to determine the safety and pharmacokinetic profile of the compound.
A number of Phase II studies are planned in several of the major tumour types and are projected to begin in this calendar year.
Data presented at the 97th Annual Meeting of the American Association for Cancer Research (AACR) in Washington DC indicated that TPI 287 is orally bioavailable in rats and that oral dosing of TPI 287 has antitumour activity in a mouse xenograft model.
In addition, data were presented from in vitro transport assays which demonstrate that TPI 287 is not a substrate for drug efflux in the MDCKII-MDR monolayer system and that TPI 287 demonstrates increased potency in cell cytotoxicity assays with MDR 1+ and mutant tubulin expressing tumour cell lines when compared to paclitaxel.
A poster entitled "Oral Bioavailability and antitumor activity of TPI 287 -- a new taxane analog with greater activity against tumour cells with demonstrated mutant tubulin," Abstract No. 493, by David Emerson, Carol Bell, Mark Jones, Barbara Schiemann and Gilles Tapolsky was presented at the conference.
Following heart disease, cancer is the second leading cause of death in the United States. In 2005, approximately 1.4 million new cancer cases will be diagnosed and about 570,000 cancer deaths will occur in the United States.
The overall survival rate for all types of cancer is 64 per cent. Today, there are nearly 10 million cancer survivors in the United States.
The most common types of cancer are breast, prostate, lung, and colorectal cancers, not including basal and squamous cell skin cancers.
Lung, breast, prostate, and colorectal cancers are also the four most common causes of cancer death in the United States. In fact, lung cancer remains the leading cause of cancer death and will account for more than 175,000 deaths in 2005.