RESUMO
The purpose of this study was to evaluate gemcitabine plus paclitaxel in heavily pretreated patients with metastatic breast cancer (MBC). Patients with MBC with second or third relapse to anthracycline-containing regimens received a 3-hour infusion of paclitaxel 175 mg/m2 on day 1, and gemcitabine 1.0 g/m2 on days 1, 8, and 15, every 28 days. Because of unacceptable thrombocytopenia seen in the first 5 patients, the gemcitabine schedule was changed to days 1 and 8 (G-1,8) for the remainder of the study, every 21 days. Twenty-nine patients (median age, 46 years; range, 32-68 years) received 137 cycles (median: 4 per patient). The regimen was well tolerated. World Health Organization grades III and IV thrombocytopenia were observed in 5 (18.5%) of the first 27 cycles (G-1,8,15), and in 6 (5.4%) of the 110 subsequent cycles (G-1,8)--p = 0.04 for the difference between schedules. Five patients had grade I and two had grade III neuropathy. Eight patients had grade III neutropenia, two had grade IV neutropenia associated with fever (G-1,8,15), and eight had grades I and II myalgia and fatigue. There were 16 (55%) objective responses (95% CI 36-73%); 5 (17%) complete responses, 11 (38%) partial responses (95% CI 3-30% and 19-56%, respectively), and 6 (20.5%) patients with stable disease. Median response duration was 8 months (range, 4-26 months). Median overall survival was 12 months (range, 4-28+ months), and 1-year and 2-year survival rates were 45% and 30%, respectively. This phase II study demonstrated a manageable toxicity profile with the gemcitabine day 1, 8 schedule in combination with paclitaxel and significant and promising activity in heavily pretreated patients with MBC. A confirmatory phase III trial is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Terapia de Salvação , GencitabinaRESUMO
In a phase II trial, 29 patients with anthracycline-pretreated or anthracycline-resistant metastatic breast cancer in whom anthracycline-containing first- or second-line chemotherapy failed received combination paclitaxel (Taxol)/gemcitabine (Gemzar). The initial regimen of paclitaxel at 175 mg/m2 on day 1 and gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle was given to five patients for a total of 27 cycles. The regimen resulted in excessive thrombocytopenia and was subsequently changed to gemcitabine at the same dose on days 1 and 8 of a 21-day cycle, with study treatment being given for a maximum of eight cycles. This regimen was well tolerated. Further evaluation of this regimen in minimally and heavily pretreated patients with advanced breast cancer is warranted.