Gemcitabine in metastatic breast cancer

Gemcitabine is a pyrimidine antimetabolite which has shown activity in metastatic breast cancer both as a single agent, but also In various combination regimens. It is characterized by a unique mechanism of action which includes cytotoxic self-potenflation, masked DNA chain termination and potent inhibition of DNA repair. The clinical application of gemcitabine is supported by a favorable toxicity profile. In metastatic breast cancer, several Phase II trials document the activity of gemcitabine in pretreated and unpretreated patients. In a single Phase III trial performed in elderly patients not pretreated, gemcliabine was inferior to epirubicin. High activity has, however, been obtained by the combination of gemcitabine with taxanes such as paclitaxel or docetaxel. In a randomized trial performed in anthracycline-pretreated patients, the combined use of gemcitabine and paclitaxel induced a significant improvement not only of response rate and time to disease progression, but also caused a significant increase in quality of life and survival when compared with paclitaxel alone. The combination of gemcitabine with vinorelbine and cisplatin has been validated in numerous Phase II trials and promises reliable activity in anthracycline- and/or taxane-pretreated patients. Triple-agent regimens such as gemcitabine/epirubicin/paciffaxel provided consistently high response rates in Phase II trials, but failed to show superiority over the 5-fluorouracil/epirubicin/cyclophosphamide regimen in a randomized Phase III trial. Based on high response rates and pathological complete remission rates achieved by preoperative induction therapy with gemcitabine/epirubicin/taxang regimens, ongoing trials focus on the incorporation of gemcitabine into neoadjuvant and adjuvant regimens.