Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness

BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources OBJECTIVE: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. DESIGN, SETTING AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75 mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. CONCLUSIONS: Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body

FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases.

PURPOSE: FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases. MATERIALS AND METHODS: We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis. RESULTS: Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of 106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only metastasis and in only the primary tumor, respectively. Overall and recurrence-free survival was not related to FGFR3 expression. CONCLUSIONS: FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy

The effect of noise on deoxyglucose uptake into inner ear tissues of the mouse

Die Aufnahme von Deoxyglukose in das Innenohrgewebe wurde bei Mäusen untersucht. Sechzig Minuten nach einmaliger i.v. Injektion von 5 mCi 2-Deoxy- D [ 3 H]-Glukose/kg Körpergewicht wurden Stria vascularis/Ligamentum spirale und Cortisches Organ sowie andere Körpergewebe seziert und ihre Radioaktivität gemessen. Die Aufnahme in das Innenohrgewebe war 3–5mal niedriger als in Herz oder Gehirn. Das Verhältnis von Deoxyglukose-6-Phosphat zu Deoxyglukose war 60∶40, und die Substanzen wurden mit einer kurzen Halbwertszeit (ca. 60 min) aus dem Innenohr ausgeschieden. Beschallung mit white noise (100 dB) während des radioaktiven Pulses führte zu einer 50%igen Erniedrigung der Einbaurate in die Innenohrgewebe. The uptake of deoxyglucose into inner ear tissues was studied in the mouse. Sixty minutes after a single i.v. injection of 5 mCi 2-deoxy- D -[ 3 H]glucose/kg body weight, stria vascularis/spiral ligament and organ of Corti as well as other body tissues were dissected and analyzed for radioactivity. Uptake into inner ear tissues was three to five times lower than into brain or heart. The ratio of deoxyglucose-6-phosphate to deoxyglucose was 60∶40 and the compounds were eliminated from the inner ear with a half life of approximately 60 min. Exposure to 100 dB of white noise during the radioactive pulse decreased uptake of deoxyglucose into both stria vascularis/spiral ligament and organ of Corti by 50%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47265/1/405_2004_Article_BF00456146.pd