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.