Role of gemcitabine in the treatment of advanced and metastatic breast cancer

Gemcitabine is an antimetabolite drug with proven antitumor
activity and tolerability in metastatic breast cancer. In a total
of nine studies, gemcitabine monotherapy has reached response rates
of up to 37% in the first-line setting, 26% in the second-line
setting, and 18% or better in the third-line setting. Gemcitabine
is an excellent choice for combination therapy by its unique
mechanism of action and favorable toxicity profile, thus limiting
the risk of pretreatment-related drug resistance and overlapping
toxicity, and by its potential for synergistic interaction with
some combination partners as indicated in preclinical studies.
Numerous phase II clinical studies have combined gemcitabine with
other active agents such as the taxanes, vinorelbine, vindesine,
cisplatin, 5-fluoro-uracil, as well as anthracyclines across
various regimens and conditions of pretreatment. Most of these
two-drug combinations have consistently demonstrated higher
efficacy than either single agent, particularly in pretreated
patients. Even higher efficacy has been obtained with triple-drug
regimens including gemcitabine, anthracyclines (epirubicin or
doxorubicin), and paclitaxel; these regimens have yielded overall
response rates of 58-92% as first-line treatment. In view of these
results, gemcitabine may be regarded as a valuable alternative to
the palliative treatment of metastatic breast cancer, and an
excellent option for the development of effective combination
treatment not only in first-line therapy, but also for intensively
pretreated patients previously exposed to anthracyclines and/or the
taxanes. Copyright (C) 2003 S. Karger AG, Basel.