Abstract
<div>Abstract<p><b>Purpose:</b> To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [<sup>18</sup>F]-3′deoxy-3′-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.</p><p><b>Experimental Design:</b> This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II–IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles).</p><p><b>Results:</b> Average and maximum tumor standardized uptake values at 60 minutes (SUV<sub>60,av</sub> and SUV<sub>60,max</sub>) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 × 10<sup>−5</sup> m<sup>2</sup>/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (<i>P</i> = 0.0003 for SUV<sub>60,av</sub> and <i>P</i> = 0.0002 for SUV<sub>60,max</sub>). Reduction in tumor SUV<sub>60,av</sub> was associated with target lesion size changes midtherapy (Pearson <i>R</i> for SUV<sub>60,av</sub> = 0.64; <i>P</i> = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV<sub>60,av</sub> in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, <i>K</i><sub>i</sub>). Docetaxel significantly reduced <i>K</i><sub>i</sub> by 51.1% (±28.4%, <i>P</i> = 0.0009).</p><p><b>Conclusion:</b> Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non–FLT-PET response. <i>Clin Cancer Res; 17(24); 7664–72. ©2011 AACR</i>.</p></div>
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