Chemosensitivity testing as an aid to anti-cancer drug and regimen development.

The ATP-based chemosensitivity assay has proved particularly useful for the evaluation of new anti-cancer agents and combinations. The majority of our publications in this area have concentrated on topoisomerase inhibitors. Comparison of mitoxantrone with doxorubicin convinced us that these two agents were not completely cross-resistant and led to the design of the mitoxantrone + paclitaxel regimen which is now in clinical practice. Re-assessment of treosulfan in uveal melanoma led to the design of a new regimen combining this alkylating agent with gemcitabine, again with rapid introduction of this combination to clinical practice. The assay has recently been used to examine the concentration-activity curve to determine which tumours might benefit from liposomal preparations capable of delivering 4-16 times the standard dose without cardiotoxicity. Assay-directed use of Caelyx is producing encouraging results, and we are now examining this drug in combination with others. We recently showed that XR5000, a combined inhibitor of topoisomerase I and II, was effective against melanoma as well as ovarian cancer, but at concentrations which were unlikely to be achieved in patients. These data confirm our suggestion that use of the assay could reduce the time to introduction of new anti-cancer drugs and the cost of this process.