Estefanía Arévalo

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.

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.

Safety and efficacy of maintenance therapy (MT) with a nonspecific cytochrome-P 17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castratation-resistant prostate cancer (mCRPC) patients.

145 Background: ACRPC causes >30,000 deaths/year in the USA. The front-line treatment consists of docetaxel-based chemotherapy (D). 50% of patients (pts) show at least a 50% PSA decline during D and >15% show a partial response (R) in measurable disease. However, most of these pts present progression (P) after a median of 6-8 months (m). mCRPC remains driven by ligand-dependent androgen (A) receptor signaling. Ketoconazole (K) is a nonspecific cytochrome-P 17 inhibitor (CYP17i) able to block adrenal A synthesis. Low-dose K (LDK), (200 mg, t.d.s) has shown interesting activity in mCRPC after P to androgen deprivation therapy (ADT). The FDA recently granted approval to Abiraterone acetate, a selective CYP17i showing a survival benefit after P to D. The role of a CYP17i in the maintenance setting after response/stabilization to D has never been studied. METHODS 38 mCRPC pts starting D after P to ADT maintained LHRHa and additionally received a median of 7 cycles (3-12) of front-line three-weekly D (75 mg/m2) plus daily prednisone (10 mg). 20/38 pts showing no progression to D were enrolled. One month after the last D cycle 10 pts were assigned to MT with LDK plus prednisone (10 mg daily) and continued to receive LHRHa while the 10 pts in the control arm continued on LHRHa alone. Progression-free survival (PFS) was the primary endpoint of the study. RESULTS After a median follow-up of 27 m, all pts in the control arm progressed after D treatment while 8/10 pts progressed to MT. PFS from D initiation was 11.4 m for MT and 8.9 m for control arm (p=0.025). Toxicity profiles showed no significant differences between both arms. No pts discontinued LDK for toxicity reasons. CONCLUSIONS To our knowledge, this is the first study testing a CYP17i for MT after response/stabilization to D in mCRPC. Although this is a small cohort of pts and a longer follow-up is needed, these preliminary data show a significant benefit in PFS of more than 2 months with LDK MT compared to no MT after D with a favorable toxicity profile. Thus, a further analysis in a larger series and the potential impact of this PFS benefit on the overall survival is warranted.