Fast track — ArticlesGemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial
Introduction
Anthracyclines and taxanes are the current standard treatments in the management of hormone-unresponsive metastatic breast cancer. Anthracycline combinations such as fluorouracil-doxorubicin-cyclophosphamide, fluorouracil-epirubicin-cyclophosphamide, and doxorubicin-cyclophosphamide are commonly used as first-line regimens for metastatic breast cancer. The results achieved with these treatments have been objective responses in more than 50% of patients, and complete responses in about 10% of patients.1 Taxanes (paclitaxel and docetaxel) are also very active agents in metastatic breast cancer, and are extensively used both in combination with anthracyclines or after anthracycline failure.2, 3, 4, 5 Chemotherapy regimens that include anthracyclines and taxanes are now the standard adjuvant treatment for high-risk early breast cancer.6, 7, 8 Such regimens have been used increasingly worldwide in this setting, which has led to a restricted use of these drugs in patients with disease relapse. New cytotoxic treatments for disseminated disease, such as gemcitabine, capecitabine, and vinorelbine are now available to treat patients who have been previously treated with anthracyclines and taxanes.9, 10, 11 Vinorelbine was extensively used in the 1990s in Europe and the USA in patients who were pretreated with anthracyclines and taxanes. Gemcitabine was introduced in the late 1990s and was also tested in patients with metastatic breast cancer and showed moderate antitumour activity and low toxicity. On the basis of the single-agent activities of vinorelbine and gemcitabine and the paucity of overlapping extra-haematological toxic effects, phase II trials12, 13, 14, 15, 16, 17, 18, 19 have tested the activity of different schedules of combinations of these two drugs, and have found encouraging antitumour activity. In 1998, the Spanish Breast Cancer Research Group (GEICAM) published the results of a phase II trial20 with gemcitabine plus vinorelbine with a response rate of 44% (95% CI 24–65) and a median time-to-treatment failure of 17 weeks months (14–20 weeks).
To assess the contributing effect of gemcitabine to this promising antitumour activity, we undertook a randomised, phase III, multicentre study that compared gemcitabine plus vinorelbine with vinorelbine alone in patients with metastatic breast cancer who had been previously treated with anthracyclines and taxanes. This report summarises the final results of this trial (GEICAM 2000–04).
Section snippets
Patients and procedures
Women with histologically confirmed locally recurrent and metastatic breast cancer who were not amenable to curative surgery or radiotherapy and who had undergone previous treatment with anthracyclines and taxanes were eligible to enter into the trial. Other eligibility criteria included: a maximum of two previous chemotherapy regimens for metastatic disease; age at least 18 years; WHO performance status of 2 or lower; sufficient bone marrow reserve (neutrophil count ≥2×109/L, platelets ≥100×109
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