BackgroundThere is growing interest in the use of diammine silver fluoride (DSF) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world. While DSF has been available in various formulations for many years, most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized.MethodsThis preliminary study determined the applied doses (3 teeth treated), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 μL).ResultsOver the 4 hour observation period, the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 h and 2.5 h for fluoride and silver, respectively.ConclusionsFluoride exposure was below the U.S. Environmental Protection Agency (EPA) oral reference dose. Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime, but for occasional use was well below concentrations associated with toxicity. This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults.Clinical trials registrationNCT01664871.
1091 Background: Estrogen modulates angiogenesis via effects on endothelial cells with subsequent induction of vascular endothelial growth factor (VEGF). VEGF promotes tumor growth and is associated with poor response to antiestrogen therapy. This trial was designed to evaluate the progression-free survival (PFS) of bevacizumab (B) in combination with anastrozole (A) or fulvestrant (F) as first-line endocrine therapy (ET) in metastatic breast cancer (MBC). Methods: Eligibility criteria: no prior hormonal or chemotherapy for MBC, measurable or evaluable disease, normal LVEF, post-menopausal. Treatment: Arm A: anastrozole 1 mg po QD in pts who were a) ET naïve, b) ≥ 12 months from adjuvant ET, and c) intolerant of or progressed on prior tamoxifen. Arm B: fulvestrant 500 mg D1 and 250 mg D15 IM loading dose followed by 250 mg q28 days in pts who were a) < 12 months from adjuvant aromatase inhibitors (AIs), b) intolerant of or progressed on AIs, and c) MD's discretion. Bevacizumab 10 mg/kg IV D1 q2 weeks was given in both arms. Trastuzumab permitted in HER-2+ pts only. Response assessments were q8 weeks; pts were treated until disease progression or toxicity. Results: 79 pts were enrolled fromNovember 2006 to November 2008. 42 pts are evaluable for response and toxicity, Arm A - 25 pts and Arm B - 17 pts. Median age was 64, ECOG PS 0 - 55%, 1- 43 %, adjuvant chemo 27%, adjuvant hormonal -38%, hormone receptor status: ER+/PR+ 80%, ER+/PR- 14%, ER-/PR+ 2 %. HER-2+ 5 pts, 31% had ≥ 2 metastatic disease sites predominately lung and bone only disease - 40%. Median # cycles - 4. 24% achieved a partial response and 57% stable disease; 7 pts progressed. G3 hypertension (12%) was the most common toxicity. Median PFS for Arm A was 16.3 months and has not yet been reached for Arm B. Conclusions: Bevacizumab in combination with anastrozole or fulvestrant is feasible and well tolerated with no unanticipated toxicities. The addition of bevacizumab resulted in prolongation of the median PFS to16.3 months with anastrozole as compared to the 7–9 month historical control PFS reported for first-line AI monotherapy in MBC. Further evaluation of bevacizumab endocrine combinations is warranted. [Table: see text]
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