Phase II Trial of the Use of Paclitaxel and Gemcitabine as a Salvage Treatment in Metastatic Breast Cancer

Abstract

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.

The Efficacy and Safety of Gemcitabine Plus Paclitaxel Compared to Doxorubicin Plus Cyclophosphamide as Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

“…Two patients developed grade 4 neutropenia and one patient grade 4 thrombocytopenia [12]. The safety and effectiveness of combination chemotherapy with GP was confirmed in other phase II studies [16][17][18].…”

Phase II Study of Gemcitabine plus Cisplatin in Patients with Anthracycline- and Taxane- Pretreated Metastatic Breast Cancer

“…For the use of gemcitabinedocetaxel, an RR of 36∼79% and a TTP of 7∼8 months for first-line to third-line treatment have been reported (21)(22)(23). For the use of gemcitabine-paclitaxel, an RR of 55∼66.7% and a TTP of 11 months for first-line to third-line treatment have been reported (24,25). For the use of gemcitabine-paclitaxel-trastuzumab, an RR of 52.5% and a TTP of 13.7 months for first-line treatment for HER2-positve cases have been reported (20).…”

Role of Gemcitabine in the Treatment of Advanced and Metastatic Breast Cancer

“…Toxicities are manageable, with neutropenia being the main toxicity. The response rate of 55% obtained in anthracycline-pretreated patients [54] may be particularly appreciated in view of the low response rate to single-agent paclitaxel (16%) observed after doxorubicin failure in a phase III study [3]. Although preclinical data do not provide an established basis for synergistic drug interaction, these clinical data clearly support the use of this combination.…”

“…Murad et al [54] conducted a trial in patients who relapsed a second or third time after anthracycline-based chemotherapy. Initially, a 4-week regimen of gemcitabine at 1,000 mg/m 2 and paclitaxel at 175 mg/m 2 was given on day 1 (paclitaxel only), 8 and 15.…”