Safety and efficacy of maintenance therapy with a nonspecific cytochrome P17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castration-resistant prostate cancer.

BACKGROUND: Frontline treatment of metastatic castration-resistant prostate cancer (mCRPC) consists of docetaxel-based chemotherapy. The median time to progression (TTP) from chemotherapy initiation is 6 to 8 months. Ketoconazole, a nonspecific cytochrome P17 inhibitor (CYP17i), blocks adrenal androgen synthesis. Low-dose ketoconazole (LDK), (200 mg three times daily [t.d.s]) has shown activity in mCRPC after progression to androgen deprivation. The role of a CYP17i after docetaxel treatment in the maintenance setting has been unexplored. METHODS: We identified 38 patients with mCRPC who showed progression to luteinizing hormone releasing-hormone agonists (LHRHa) and who were treated with a median of 7 cycles of frontline three-weekly docetaxel (75 mg/m(2)) plus prednisone (10 mg/d) and LHRHa. Medical charts of 20 patients who showed no progression to docetaxel were reviewed. After the last docetaxel cycle, 10 patients received LDK maintenance treatment plus prednisone (10 mg/d) and LHRHa, whereas 10 patients received LHRHa alone. TTP was the primary endpoint. RESULTS: After a follow-up of 27 months, disease in all patients receiving LHRHa alone progressed, whereas 8/10 patients progressed to maintenance therapy. Median TTP from docetaxel initiation was 11.5 months (95% confidence interval [CI], 6.3-16.6) for maintenance therapy and 9.2 months (95% CI, 8.5-9.9) for LHRHa alone (P = .047). The maintenance treatment was well tolerated. Only 1 patient experienced a grade 4 adverse event due to a nonsymptomatic pulmonary embolism. CONCLUSION: This is the first study evaluating a CYP17i for maintenance therapy after docetaxel therapy. We showed a 2-month significant benefit in TTP for patients with mCRPC treated with LDK maintenance therapy after docetaxel, with a favorable toxicity profile. A large prospective randomized study using a CYP17i is warranted.

Clinical management of small-cell carcinoma of the urinary tract: a 10-year single-center's experience.

BACKGROUND: Small-cell carcinoma (SCC) comprises 1% of primary bladder tumors and approximately 2% of prostate neoplasms. Metastatic disease at diagnosis is common, and survival outcomes are extremely poor. There is controversy about the ideal clinical management of these patients. The neuron-specific enolase (NSE) serum levels have never been studied in patients with small-cell carcinoma of the urinary tract (SCCUT). PATIENTS AND METHODS: We report the clinical outcome of 12 consecutive SCCUT patients treated during the past 10 years. We also study the NSE levels at diagnosis and during treatment. RESULTS: Patients with limited disease (LD) experienced a non-significant longer progression-free survival (PFS) and overall survival (OS) compared with extensive disease (ED) subjects. Patients with bladder SCC showed a significantly higher median PFS compared with prostate SCCUT patients (22 vs. 6 months; P = .034), although that difference did not impact on a significant longer OS. NSE levels decreased during chemotherapy administration in all patients with ED and baseline high levels. CONCLUSIONS: Our patients showed a poor prognosis as described in previous studies. A better outcome for patients with bladder SCC compared with prostate SCC could be suggested. Serum NSE levels should be further evaluated to prove its potential use in early diagnosis and treatment monitoring during chemotherapy.

Alteraciones neuropsicológicas en alcohólicos: un estudio exploratorio / Neuropsychological disorders in alcoholics: an exploratory study

En este estudio se evaluó la presencia de alteraciones neuropsicológicas en 50 pacientes alcohólicos, en comparación con un grupo de control de 50 sujetos de la población normal, apareados en edad, sexo y nivel socioeconómico. Para ello, se aplicó una batería neuropsicológica compuesta por la Escala de Memoria de Wechsler (subtest: control mental, dígitos, localización espacial y memoria lógica), el Trail Making Test de la batería Halstead-Reitan, el test de dibujo de una Figura Compleja de Rey, el test de palabras y colores de Stroop y el subtest de evocación categorial del Test Barcelona. Los resultados obtenidos reflejaron que la ejecución en la mayoría de las pruebas era equiparable en ambos grupos. Las únicas diferencias significativas entre los grupos se observaron en el subtest de memoria lógica, tanto en el recuerdo inmediato como diferido, y en el tiempo empleado en la ejecución de la copia de la Figura de Rey. En ambos casos la muestra de alcohólicos presentaba una peor ejecución, con una afectación de la memoria en cuanto a la capacidad de realizar nuevos aprendizajes. Los resultados descartaron la existencia de un déficit cognoscitivo generalizado en los pacientes alcohólicos. La ausencia de otras alteraciones cognoscitivas, sobre todo en las funciones ejecutivas, contrasta con los hallazgos de otras investigaciones

This study evaluates the presence of neuropsychological disorders in 50 alcoholic patients compared with a control group of 50 subjects from the normal population, matched on age, sex, and socioeconomic level. The neuropsychological assessment battery comprised the Wechsler Memory Scale (subtest: mental control, digits, space localisation and logical memory), the Trail Making Test from the Halstead-Reitan Battery, the Rey Complex Figure drawing test, the Stroop words and colours test and the Barcelona Test subtest on categorical evocation. The results showed that carrying out the tasks was similar for both groups. The only significant differences between the groups were observed in the logic memory subtest, both in the immediate and in the delayed memory, and in the time taken to copy the Rey figure. In both cases, the alcoholic patients fared worse, with memory being affected in respect of the ability to learn new skills. The results do not show the existence of a generalised cognitive deficit in alcoholic patients. The absence of other cognitive distortions, mainly in the executive functions, contrast with the findings of previous studies