Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age = grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy. Copyright (C) 2011 S. Karger AG, Base

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel (D2) for First-Line Treatment of Metastatic Breast Cancer

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly {[}75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia >= grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to non-hematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status. Copyright (C) 2011 S. Karger AG, Base

Bio-Functionalized Ultra-Thin, Large-Area and Waterproof Silicone Membranes for Biomechanical Cellular Loading and Compliance Experiments

Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3–4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications