ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

PURPOSE: Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS: As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT (P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION: Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer

Correction: Kanie, N., et al. Integration and Diffusion in Sustainable Development Goals: Learning from the Past, Looking into the Future. Sustainability 2014, 6, 1761?1775

The authors wish to make the following correction, due to a typographical error, to this paper [1]. On page 1761, the author name “Shunsuke Mangagi” should be “Shunsuke Managi”. [...

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: study protocol for a multicenter randomized phase II trial (the OCUU-CRPC study)

Abstract Background Enzalutamide is an oral androgen receptor targeted agent that has been shown to improve survival in PREVAIL trials and has been approved for patients with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). Meanwhile, flutamide is a non-steroidal oral anti-androgen that was commonly used before the approval of bicalutamide. The objective of the OCUU-CRPC study is to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative anti-androgen therapy (AAT) after combined androgen blockade (CAB) therapy that included bicalutamide in patients with CRPC. Methods A total of 100 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day, 4 × 40 mg capsules once daily) and flutamide (375 mg/day; 3 × 125 mg tablets thrice daily) groups. The primary endpoint for the drug efficacy is the response rate of prostate-specific antigen (PSA) (i.e., the ratio of patients whose PSA declined by ≥50% from baseline) at 3 months. Meanwhile, the secondary endpoints are PSA progression rate at 3 and 6 months, PSA response rate at 6 months, change in quality of life, PSA progression-free survival, and safety. The patient registration started in January 2015 and will end in March 2018, and the follow-up period is 6 months after the last patient registration. The main result will be reported in March 2019. Discussion In the OCUU-CRPC study, we compare the efficacy and safety of enzalutamide or alternative AAT with flutamide in participants with CRPC who were previously treated with a CAB therapy with bicalutamide. The expected results of this study will be that enzalutamide is superior to flutamide in terms of PSA response. A longer time to disease progression with enzalutamide over flutamide may translate to better overall survival. However, flutamide may be more accessible for patients owing to its lower cost than enzalutamide. Trial registration The OCUU-CRPC study was prospectively registered at clinicaltrials.gov (NCT02346578, January 2015) and University Hospital Medical Information Network (UMIN000016301, January 2015)

Transarterial chemoembolization of liver metastasis from renal cell carcinoma

A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared. There was no recurrence at 2 years, and axitinib was discontinued

A Case of Pulmonary Pleomorphic Carcinoma With Renal Metastasis

A 62-year-old man was referred to our hospital for an axillary mass. Computed tomography (CT) revealed a right axillary tumor and a left renal tumor. Needle biopsies of lung tumor and renal tumor were performed, but a definite diagnosis was impossible. Because his performance status worsened and the lung tumor grew day by day, chemotherapy with gemcitabine and cisplatin was started without definite diagnosis. However, the chemotherapy could not be continued because of interstitial pneumonia and the patient died because of the progression of disease. The final histopathologic diagnosis was pulmonary pleomorphic carcinoma based on immunohistochemical staining

Androgen Receptor Splice Variant 7 Drives the Growth of Castration Resistant Prostate Cancer without Being Involved in the Efficacy of Taxane Chemotherapy

Expression of androgen receptor (AR) splice variant 7 (AR-V7) has been identified as the mechanism associated with the development of castration-resistant prostate cancer (CRPC). However, a potential link between AR-V7 expression and resistance to taxanes, such as docetaxel or cabazitaxel, has not been unequivocally demonstrated. To address this, we used LNCaP95-DR cells, which express AR-V7 and exhibit resistance to enzalutamide and docetaxel. Interestingly, LNCaP95-DR cells showed cross-resistance to cabazitaxel. Furthermore, these cells had increased levels of P-glycoprotein (P-gp) and their sensitivity to both docetaxel and cabazitaxel was restored through treatment with tariquidar, a P-gp antagonist. Results generated demonstrated that P-gp mediated cross-resistance between docetaxel and cabazitaxel. Although the LNCaP95-DR cells had increased expression of AR-V7 and its target genes (UBE2C, CDC20), the knockdown of AR-V7 did not restore sensitivity to docetaxel or cabazitaxel. However, despite resistance to docetaxel and carbazitaxel, EPI-002, an antagonist of the AR amino-terminal domain (NTD), had an inhibitory effect on the proliferation of LNCaP95-DR cells, which was similar to that achieved with the parental LNCaP95 cells. On the other hand, enzalutamide had no effect on the proliferation of either cell line. In conclusion, our results suggested that EPI-002 may be an option for the treatment of AR-V7-driven CRPC, which is resistant to taxanes