Feasibility and safety of dose-dense docetaxel after conventional epirubicin and cyclophosphamide as adjuvant treatment for early breast cancer patients.

BACKGROUND: Although dose-dense chemotherapy may reduce breast cancer recurrence and death, phase II studies show that dose-dense docetaxel is poorly tolerated following administration of dose-dense anthracycline-based chemotherapy mainly because of cutaneous toxicity. MATERIAL AND METHODS: This pilot study was designed to explore feasibility and safety of dose-dense docetaxel after conventional anthracycline-based therapy. Treatment consisted of sequential administration of 4 cycles of 3-weekly epirubicin (90 mg/m(2)) plus cyclophosphamide (600 mg/m(2)), followed by 4 cycles of bi-weekly docetaxel with pelfilgrastim on day 2 of each docetaxel cycle. Two docetaxel dose levels were planned: 75 mg/m(2) (D75) and 100 mg/m(2) (D100). Patients could only be assigned to the higher docetaxel dose if no early treatment discontinuations due to toxicity were seen, and a median relative dose intensity of docetaxel >90% among the first 5 evaluable patients was achieved. RESULTS: Fifty three patients received 4 cycles of epirubicin/cyclophosphamide (EC). Six patients withdrew from study before commencing docetaxel: four for toxicity, and two who declined further study participation. Eight patients, 2 in the first dose level and 6 in the second dose level, stopped treatment for toxicity after the first cycle of docetaxel and before densification. Therefore these events were not considered early treatment discontinuations. No patients required dose interruption after the second docetaxel administration. Overall 5 patients in the first dose level and 34 patients in the second dose level received 4 cycles of accelerated (dose-dense) docetaxel. No grade 3 or grade 4 toxicities occurred at the first dose level. No grade 4 toxicities occurred at the second dose level, while grade 3 toxicities occurring in >2 patients were myalgia and bone pain (5 and 8 patients respectively, 13% and 20%) and skin-nail toxicity (7 patients, 21%). No dose-reductions or significant treatment delays were required, translating to median relative dose intensity of 100% for docetaxel 75 mg/m(2), and 99% for 100 mg/m(2). CONCLUSIONS: Administration of docetaxel 100 mg/m(2) bi-weekly after conventional EC is feasible in selected early breast cancer patients. Lack of prior exposure to dose-dense anthracycline, as well as the use of stringent criteria implemented in the treatment protocol, might explain the improved safety profile and high treatment compliance observed in this study.

Most sensitive urinary cotinine cut-off level for environmental tobacco smoke exposure assessment: a pilot study.

The aim of this pilot study was to determine the most sensitive urinary cotinine level able to assess environmental tobacco smoke (ETS) exposure. 54 Florentine subjects (29 males and 25 females), reporting to be nonsmokers and exposed (E) or not exposed (NE) to ETS at home, at work or in places of recreation, were examined. The urinary cotinine concentration was determined using gaschromatographic analysis in samples collected on three consecutive days. 18 subjects (33.3%) reported to be exposed to ETS had a greater median cotinine concentration than 36 ETS-NE subjects (E = 3.3 pg/L vs NE = 2.2 microg/L, median values), with borderline statistical significance (P = 0.05). The 2.5 microg/L cotinine concentration was the only statistically significant cut-off (P = 0.04) discriminating between ETS-E to ETS-NE subjects, identifying 51.9% of the subjects examined as exposed (E). Considering the expanded uncertainty of measurement of the method used (20%), urinary cotinine concentrations higher than 3.1 microg/L, a value whose confidence interval is higher than our proposed cut-off of 2.5 microg/L, mean that to be sure that a subject is exposed to ETS.