Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m2 intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. Results In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). Conclusion Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.

A new ion desorption method is described that utilizes a primary beam of massive, multiply charged cluster ions to generate secondary ions of peptides in a glycerol matrix. The massive cluster ion beam is generated via electrohydrodynamic emission using a 1.5 M solution of ammonium acetate in 30% aqueous glycerol. Negative ion spectra of peptides obtained using this technique show greatly decreased relative intensities for fragment ions and 'chemical noise' background when compared to spectra obtained using a xenon atom primary beam. The near absence of fragments derived from radiation damage to the sample solution is attributed to the impact of primary particles with energies less than 1 eV/nucleon.

LBA4511 Background: The preclinical activity of vascular endothelial growth factor (VEGF) blockade, the inverse relationship of plasma and urine VEGF levels and survival in mCRPC patients (pts), and encouraging phase II data testing estramustine and docetaxel with bevacizumab suggested that VEGF blockade was an appropriate potential strategy in mCRPC. A phase III study testing the effect of adding bevacizumab to standard docetaxel and prednisone therapy administered every 3 weeks in pts with mCRPC was conducted. Methods: 1050 pts with chemotherapy naïve, mCRPC with evidence of progressive disease despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal function were eligible. Pts were prospectively randomized with equal probability to receive docetaxel (D:75 mg/m2 IV over 1 hour q 21 days), plus prednisone (P) 5 mg po BID with either bevacizumab (B:15 mg/kg given intravenously q 3 weeks following D) or placebo. All patients received dexamethasone 8 mg PO 12, 3 and 1 hour prior to D. Randomization was stratified by predicted 24 mo survival probability, age and history of prior arterial thrombotic event. The primary endpoint was overall survival (OS). The trial was designed with 86% power to detect a 21% decrease in the hazard rate of death (equivalent to an increase in median OS from 19 months to 24 months) assuming a two-sided significance level of 0.05. The primary analysis was based on the stratified log-rank statistic adjusted for the stratification factors following observation of 748 deaths. Results: See Table . Conclusions: Despite an improvement in PFS, measurable disease response and post-therapy PSA decline, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC, and was associated with greater morbidity and mortality. The median OS of pts treated with standard DP (21.5 m) was longer than previously reported (19 m). [Table: see text] [Table: see text]