LONDON Xenova Group plc said it will begin Phase II trials of XR9576 for the prevention of multi-drug resistance in cancer chemotherapy early in 1999, following the successful completion of Phase I studies, which showed the drug was safe and well tolerated.

XR9576 acts by inhibiting the P-glycoprotein (P-gp) pump, which mediates the removal of anticancer drugs from cancer cells. A method of assessing the potential activity of XR9576 used in the Phase I trial suggested that once a day dosing can inhibit the activity of the P-gp pump for up to 24 hours.

The Phase II program will study the effect of XR9576 in combination with a variety of cytotoxic drugs such as doxorubicin, paclitaxel and vincristine, and will be carried out at a number of centers in the U.S. and the U.K. Although XR9576 is a small molecule, it was administered intravenously in Phase I trials, and Xenova, which specializes in the discovery and development of small-molecule drugs from microorganisms, says it is also starting development of an oral formulation in January.

Of 3 million people diagnosed with cancer annually in the U.S., Europe and Japan, 60 percent are treated by chemotherapy. Despite initial improvement, many later relapse and fail to respond to treatment because of drug resistance. The proportion of patients that become resistant varies by tumor type, and is as high as 90 per cent. The most common mechanism is an increase in the efflux of a drug from the cell, mediated by P-gp, which is believed to cause 40 per cent of cases of drug resistance.

David Oxlade, CEO of Slough-based Xenova, said the company is in discussions with potential partners, and hopes to find a partner before the start of Phase III trials. *

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