A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

[Visible urethrotomy with a sharp incision in the treatment of post-traumatic urethral strictures]. / Die Sichturethrotomie mit scharfem Schnitt in der Behandlung posttraumatischer Harnröhrenstrikturen.

We present our results in the treatment of 13 cases of posttraumatic urethrostenosis with the aid of visual urethrotomy. In six cases very good results were achieved, in three cases, good results and in four cases, adequate results. Patients with only adequate results were submitted to a second urethrotomy.

Optimized dairy grazing systems in the northeast United States and New Zealand. I. Model description and evaluation.

Parallels exist in the recent developments of dairy systems in the Northeast United States and New Zealand because of greater use of pasture grazing and feed supplements, respectively. Lessons can be learned from each system. However, major differences exist between the regions in the patterns of pasture production, the costs of supplementary feed, and milk prices. These differences affect the optimum use of feed. In this paper, a linear programming model developed to determine optimum feeding strategies for dairy systems in each country is presented. The model optimizes grazing management (rotation lengths) and the conservation of pasture subject to constraints on their use. Other feed resources include N fertilizer, grain, corn silage, and alfalfa silage. All feeds are represented in energy terms. The substitution of pasture intake by grain and forage supplements is included, and cow performance can be optimized by choosing from 73 seasonal calving herds that vary in calving date, lactation length, and daily milk production. The model predicts that marginal responses to grain feeding are between 1.35 and 1.8 kg of milk/kg of grain dry matter supplement, well within the range of responses reported in the literature. Evaluation of the model against data from nine grazing system treatments in New Zealand and two in Pennsylvania showed that model predictions averaged +3% (New Zealand) and +0.04% (Northeast) of measured milk production. The model could be used with confidence to study systems in both the Northeast United States and New Zealand.