Background Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy. Many mCRPC patients never receive chemotherapy and thus cannot benefit from abiraterone acetate; we evaluated this agent in mCRPC patients who had not received chemotherapy. Methods In this double-blind study, 1088 patients were randomized 1:1 to abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. Co-primary end points were radiographic progression-free survival (rPFS) and OS. Secondary end points measured clinically relevant landmarks of mCRPC progression. Patient-reported outcomes included pain progression and quality of life. Results The study was unblinded after a planned interim analysis (IA) at 43% of OS events. Treatment with abiraterone acetate-prednisone resulted in a 57% reduction in the risk of radiographic progression or death (hazard ratio [HR], 0.43; 95% confidence interval [CI]: 0.35 to 0.52; P<0.001; 13% OS events IA) and an estimated 25% decrease in the risk of death (HR, 0.75; 95% CI: 0.61 to 0.93; P=0.009; 43% OS events IA). Secondary end points supported superiority of abiraterone acetate-prednisone: time to cytotoxic chemotherapy initiation, opiate use for cancer-related pain, prostate-specific antigen progression (all P<0.001) and performance status deterioration (P=0.005). Self-reported time to pain progression and patient functional status degradation favored abiraterone acetate-prednisone (P=0.05 and P=0.003). Grade 3/4 mineralocorticoid-related adverse events and liver function test abnormalities were more common with abiraterone acetate-prednisone. Conclusions Abiraterone acetate produces OS and rPFS benefits, as well as significant delays in clinical deterioration and initiation of chemotherapy, in mCRPC.

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A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed.

See also van den Berg YW, Reitsma PH. Not exclusively tissue factor: neutrophil extracellular traps provide another link between chemotherapy and thrombosis. This issue, pp 2311–2. Summary.  Background: Thrombosis is a common complication for breast cancer patients receiving chemotherapy. However, the mechanisms by which breast cancer chemotherapeutic agents increase this risk are largely uncharacterized. Nucleic acids released by injured cells may enhance coagulation via the activation of the contact pathway. Objectives: In this study, we examined the effects of breast cancer chemotherapy agents on the release of cell‐free DNA (CFDNA) and its relationship to thrombin generation using in vitro and in vivo methods. Methods: CFDNA release and thrombin‐antithrombin (TAT) levels were measured in plasma of breast cancer patients and healthy mice receiving chemotherapy. Venous whole blood and cultured cells were exposed to chemotherapy and CFDNA release and levels of DNA‐histone complexes were measured. The procoagulant activity of isolated CFDNA was measured with calibrated, automated thrombin generation. Results: Breast cancer patients receiving chemotherapy had elevated levels of CFDNA 24 h post‐chemotherapy, a time‐point at which elevated thrombin‐antithrombin levels have been previously reported. Treatment of healthy mice with doxorubicin, epirubicin and 5‐fluorouracil increased CFDNA release, with a corresponding elevation in TAT complex formation. Venous whole blood and neutrophils incubated with chemotherapeutic agents had elevated CFDNA in plasma or cell supernatants. In addition, incubation of venous whole blood with chemotherapy decreased histone‐DNA complex levels. CFDNA released from epirubicin‐treated whole blood significantly elevated thrombin generation in a dose‐dependent manner, and involved activation of the contact pathway. Conclusions: Release of CFDNA from chemotherapy‐injured cells may represent a novel mechanism by which thrombosis is triggered in cancer patients.