Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Electrochemical determination with a long-length carbon nanotube electrode of quercetin glucosides in onion, apple peel, and tartary buckwheat.

Since the intake of quercetin glucosides has healthy benefits, the analysis of quercetin glucosides in food is useful. The electrochemical determination of individual quercetin glucosides (quercetin-3-glucoside (Q3G), quercetin-4'-glucoside (Q4'G), and quercetin-3,4'-diglucoside (Q34'G)) in food is carried out. For the detection of quercetin glucosides, a long-length carbon nanotube electrode offers attractive properties such as well-defined current peaks, high sensitivity, and high reproducibility. Cyclic voltammetry (CV) demonstrates distinct and specific peak currents: the oxidation peaks at +0.37, +0.45, and +0.78 V are assigned to the catechol group in the B-ring of Q3G, the 3-hydroxy group in the C-ring of Q4'G, and the resorcinol group in the A-ring of both Q4'G and Q34'G, respectively. Currents, which are determined by CV, of individual quercetin glucosides at the peak potential are proportional to the concentrations of onion, apple peel, and tartary buckwheat, which show good agreement with those obtained by high-performance liquid chromatography.

Polyphenol Analysis in Black Tea with a Carbon Nanotube Electrode.

An electrochemical analysis of polyphenols (theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), theaflavin-3,3'-digallate (TF3), and epigallocatechingallate (EGCG)) in a black tea infusion is demonstrated. The characterization of each polyphenol in a solution containing only a single type of polyphenol for a redox reaction at the CNT electrode with cyclic voltammetry (CV) was conducted. The oxidation peak at around +0.30 V for TF1 is assigned to catechol group in a benzotropolone ring. The oxidation peak at around +0.35 V for TF2A, TF2B, and TF3 is assigned to both of the catechol groups in the benzotropolone ring and the pyrogallol group in the gallate ring. The oxidation peak at around +0.35 V for EGCG is assigned to a pyrogallol group in the gallate ring. Current changes of those individual polyphenols at the peak potential are proportional to their concentrations (linear range 0.28 - 94 µM; detection limit 0.11 µM). The CV curve for real black tea, which is mainly composed of a mixture of the mentioned five compounds, is produced by the sum of those. The current change of the mixture solution of polyphenols is also proportional to the mass concentration of the total polyphenols and the sensitivity defined as the slope of current vs. concentration plot is independent of the ratio of the individual polyphenols. This indicates that the peak current at around +0.35 V can quantify the total amount of polyphenols in a black tea. Additionally, the shape of the CV curve can roughly estimate the ratio of [catechins]/[theaflavins]. The values for real samples determined from CVs show good agreement with that obtained by high-performance liquid chromatography.

Separationless and Adsorptionless Quantification of Individual Catechins in Green Tea with a Carbon Nanotube-Carboxymethylcellulose Electrode.

We demonstrate the electrochemical quantification of individual catechins (epicatechin, EC; epigallocatechin, EGC; epicatechingallate, ECG; and epigallocatechingallate, EGCG) in a green tea infusion without a separation process nor any adsorption complication. In the detection of catechins, long-length carbon nanotube (CNT)-carboxymethylcellulose (CMC) thin-film electrodes have attractive properties, such as well-defined current peaks, high reproducibility from sample to sample, high repeatability, and low background current. Cyclic voltammograms (CVs) for real green tea, which is mainly composed of a mixture of the four catechins, are produced by the sum of those catechins. A set of three specific peaks in the CVs of the real green tea samples, as catechin-mixture solutions, was used for quantification of the individual catechins. The CVs of the real samples are similar to the CVs of intentionally prepared mixture solutions with the catechin-component ratios determined by high-performance liquid chromatography (HPLC). The values for the real samples determined from the CVs show good agreement with those obtained by HPLC. The novelty of the work is the demonstration of the usefulness of the CNT-CMC electrode and the separationless quantification of individual catechins in green tea for the first time.

[Alternative antiandrogen therapy with flutamide in patients with castration-resistant prostate cancer : a single center experience].

Alternative Antiandrogen Therapy with Flutamide in Patients with Castration-Resistant Prostate Cancer : A Single Center Experience We analyzed the clinical effects of flutamide (FLT) as a second-line agent for maximum androgen blockade (MAB) in patients with castration-resistant prostate cancer who received bicalutamide (BCL) as the first-line MAB agent. This study included 44 cases with progressive prostate cancer who had relapsed after first-line MAB, with BCL at 80 mg/day. After checking for antiandrogen withdrawal syndrome (AWS), they were given FLT at 375 mg/day as second-line MAB. A partial response (prostate-specific antigen [PSA] decline ≧50%) and no change (PSA decline of 0-50% or increase ＜25%) by second-line MAB with FLT were achieved in 34.1% (15/44) and 25.0% (11/44), respectively. The median duration of PSA response was 8.2＋/-4.5 months. In multivariate analysis, Gleason score (≦7 vs ≧8), the first-line response (CR vs PR＋NC), and the second-line response (PR＋NC vs PD) were significantly predictive of cause-specific survival from first-line hormonal therapy relapse to cancer death. Our results confirm previous findings that alternative antiandrogen therapy is effective as a second-line hormonal therapy.

One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients.

BACKGROUND: Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. METHODS: A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI). RESULTS: There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328). CONCLUSION: Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.

[Mass screening for prostate cancer at Ikeda City in Osaka Prefecture--results of screening with PSA alone between 2003 and 2007].

PURPOSE: Since 2003, screening with prostate specific antigen (PSA) has been conducted to detect prostate cancer. We investigated the results between 2003 and 2007. PATIENTS AND METHODS: Screening with PSA alone was performed for males aged over 50 years who desired prostate cancer screening. We used a PSA cutoff value of 4.00 ng per milliliter. RESULTS: In 2003, there were 18,161 males aged over 50 years in Ikeda City. 3,738, 3,905, 4,129, 4,410, and 4,515 of the males underwent PSA screening in 2003, 2004, 2005, 2006, and 2007. The rate of elevated PSA levels was 7.9%-9.8% (median 9.1%). 161, 81, 70, 75 and 60 of the males visited us for secondary screening, and prostate biopsy was performed in 130 (80.7%), 57 (70.4%), 45 (64.3%), 38 (50.7%), and 42 (70.0%). Prostate cancer was detected in 91, 33, 29, 20 and 25 males, respectively. These values corresponded to 2.43%, 0.85%, 0.70%, 0.45% and 0.55% of the males who underwent primary screening. The incidence of prostate cancer was 0.96% during the 5 years. Clinical stage was B in 137 (69.2%), C in 52 (26.3%), D in 7 (3.5%), and unknown in 2. Surgery was performed in 87 (43.9%), endocrine therapy in 61 (30.8%), irradiation in 37 (18.7%), and follow up without treatment in 7 (3.5%). Treatment for 6 (3.0%) is unknown because they desired treatment at another hospital. CONCLUSIONS: 198 males were diagnosed with prostate cancer between 2003 and 2007. The clinical stage B was present in 137 (69.2%), and the early treatment was achieved. This may lead to a future decrease in the mortality rate.