PURPOSE: Paclitaxel (PACL) plus gemcitabine (GEM) is an effective regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged GEM infusion at a fixed dose rate (FDR) of 10 mg/m²/min produces higher levels of intracellular active metabolites of GEM when compared with a standard 30-min infusion. In the present phase I/II trial, we investigated the association of FDR GEM plus PACL. METHODS: 1,200 mg/m² was the dose of GEM recommended for the phase II study, in which patients received PACL at 150 mg/m², followed by FDR GEM at 1,200 mg/m² (total GEM infusion time = 120 min), both drugs administered biweekly. RESULTS: Forty-two anthracycline-pretreated advanced breast cancer patients with disease recurrence following at least one line of chemotherapy were enrolled. Two (4.8%) and 12 (33.3%) patients experienced a complete and partial response, respectively, for an overall response rate of 38.1% (95% CI 23.4-52.8%). Median progression free survival and overall survival were 5 and 19.9 months, respectively. No statistically significant association was noted between in situ protein expression of RRM1 and BRCA1 (as assessed by immunofluorescence combined with automated quantitative analysis) and response to treatment in 15 patients with tissue available for analysis. Toxicity was mostly mild to moderate, mainly consisting of G3-G4 neutropenia (9.6%) and hypertransaminasemia (9.5%). CONCLUSIONS: Biweekly FDR GEM in combination with PACL is an active and safe regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged infusion regimen of GEM does not seem to improve the efficacy of a standard 30-min infusion.
PURPOSE:Paclitaxel (PACL) plus gemcitabine (GEM) is an effective regimen for advanced breast cancerpatients pretreated with anthracyclines. A prolonged GEM infusion at a fixed dose rate (FDR) of 10 mg/m²/min produces higher levels of intracellular active metabolites of GEM when compared with a standard 30-min infusion. In the present phase I/II trial, we investigated the association of FDR GEM plus PACL. METHODS: 1,200 mg/m² was the dose of GEM recommended for the phase II study, in which patients received PACL at 150 mg/m², followed by FDR GEM at 1,200 mg/m² (total GEM infusion time = 120 min), both drugs administered biweekly. RESULTS: Forty-two anthracycline-pretreated advanced breast cancerpatients with disease recurrence following at least one line of chemotherapy were enrolled. Two (4.8%) and 12 (33.3%) patients experienced a complete and partial response, respectively, for an overall response rate of 38.1% (95% CI 23.4-52.8%). Median progression free survival and overall survival were 5 and 19.9 months, respectively. No statistically significant association was noted between in situ protein expression of RRM1 and BRCA1 (as assessed by immunofluorescence combined with automated quantitative analysis) and response to treatment in 15 patients with tissue available for analysis. Toxicity was mostly mild to moderate, mainly consisting of G3-G4 neutropenia (9.6%) and hypertransaminasemia (9.5%). CONCLUSIONS: Biweekly FDR GEM in combination with PACL is an active and safe regimen for advanced breast cancerpatients pretreated with anthracyclines. A prolonged infusion regimen of GEM does not seem to improve the efficacy of a standard 30-min infusion.
Authors: Teresa Gamucci; Andrea Michelotti; Laura Pizzuti; Lucia Mentuccia; Elisabetta Landucci; Isabella Sperduti; Luigi Di Lauro; Alessandra Fabi; Giuseppe Tonini; Valentina Sini; Nello Salesi; Ilaria Ferrarini; Angela Vaccaro; Ida Pavese; Enzo Veltri; Luca Moscetti; Paolo Marchetti; Patrizia Vici Journal: J Cancer Date: 2014-03-20 Impact factor: 4.207