No abstract

BACKGROUNDThe efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castrationresistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODSWe randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTSA total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imagingbased progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgensignaling-targeted inhibitor. No new safety signals were observed. CONCLUSIONSCabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD ClinicalTrials.gov number, NCT02485691.

No abstract

The second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process.

Cytokeratins are released from carcinoma cells by unclear mechanisms and are commonly used serum tumor markers (TPA, TPS, and CYFRA 21-1). We here report that soluble cytokeratin-18 (CK18) is released from human carcinoma cells during cell death. During necrosis, the cytosolic pool of soluble CK18 was released, whereas apoptosis was associated with significant release of caspase-cleaved CK18 fragments. These results suggested that assessments of different forms of CK18 in patient sera could be used to examine cell death modes. Therefore, CK18 was measured in local venous blood collected during operation of patients with endometrial tumors. In most patient sera, caspase-cleaved fragments constituted a minor fraction of total CK18, suggesting that tumor apoptosis is not the main mechanism for generation of circulating CK18. Monitoring of different CK18 forms in peripheral blood during chemotherapy of prostate cancer patients showed individual differences in the patterns of release. Importantly, several examples were observed where the increase of apoptosis-specific caspase-cleaved CK18 fragments constituted only a minor fraction of the total increase. These results suggest that cell death of epithelially derived tumors can be assessed in patient serum and suggest that tumor apoptosis may not necessarily be the dominating death mode in many tumors in vivo.