The rational for this trial is given by the knowledge that gemcitabine acts as a potent
inhibitor of DNA repair and therefore may prevent adequate repair of platin-induced DNA
damage. Gemcitabine is an excellent choice for combination therapy by its unique mechanism of
action and favourable toxicity profile. The combination of gemcitabine and cisplatin was
shown to be effective in several trials, producing response rates of 30-52 % in patients with
pretreated metastatic breast cancer. To improve on tolerability and handling of the regime
carboplatin may be the more appropriate choice for treatment. The mechanism of action of
carboplatin is very similar to that of cisplatin. The rational for combining gemcitabine and
carboplatin is based on their single-agent activities in metastatic breast cancer, the
activity of this combination in other malignancies and on the fact that carboplatin has
demonstrated efficacy comparable with cisplatin in several tumor types.