A phase 2 multimodality trial of docetaxel/prednisone with sunitinib followed by salvage radiation therapy in men with PSA recurrent prostate cancer after radical prostatectomy.

BACKGROUND: In men with high Gleason PC and rapid PSA progression after surgery, failure rates remain unacceptably high despite salvage radiation. We explored a novel multimodality approach of docetaxel with anti-angiogenic therapy before salvage radiotherapy (RT). METHODS: This was a phase 2 single-arm prospective open-label trial with historic controls. Eligible men had a rising PSA of 0.1-3.0 ng ml(-1) within 4 years of radical prostatectomy, no metastases except resected nodal disease, no prior androgen-deprivation therapy (ADT) and Gleason 7-10. Men received four cycles of docetaxel 70 mg m(-2) every 3 weeks with low dose prednisone and sunitinib 37.5 mg daily for 14/21 days each cycle, with no ADT. Salvage prostate bed RT (66 Gy) started at day 100. The primary end point was progression-free survival (PFS) rate at 24 months. Safety data, quality of life (QOL) and dose-limiting toxicities (DLTs) were measured over time. RESULTS: Thirty-four men accrued in this multi-institutional clinical trial: 24% of men were node positive, 47% were Gleason 8-10, median PSA at entry was 0.54. The trial was terminated prematurely owing to excess DLTs (nine) including grade 3 hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1) and vomiting with diarrhea (n=1). PFS rate at 24 months was 51% (95% CI: 33, 67%) with a median PFS of 26.2 months (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. CONCLUSIONS: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. Although nearly half of the men experienced durable disease control, efficacy was not greater than expected with radiation alone. The use of the intermediate end point of PFS in this salvage setting permitted an early decision on further development of this combination.

Financial crisis in a family practice residency: a successful strategy.

A family practice residency program in a California public teaching hospital was faced with a financial crisis that threatened its elimination. Hospital officials and medical leaders developed a strategy that resulted in (1) personnel reductions focused principally on hospital overhead departments, (2) reductions in faculty teaching fees, (3) increased resident and faculty productivity, (4) increased patient access to ambulatory areas, (5) decreased utilization of laboratory, radiology, respiratory, physical therapy, pharmacy, and cardiology services, and (6) more favorable contracts with providers for patient care services. The hospital met its financial objectives primarily as a result of collaborative efforts of the hospital management team and a committed faculty vested in the success of the institution.

Zinc and vitamin A: serum concentrations of zinc and retinol-binding protein (RBP) in healthy adolescents.

The concentrations of serum zinc and retinol-binding protein (RBP) have been studied with special reference to pubertal development in 132 healthy adolescents and young adults (11-26 years of age). The RBP level remained low during the first three of the five stages of puberty (mean, about 30 mg/l). When puberty degree 4 had been reached, the mean RBP level increased to nearly adult values (about 40 mg/l), the boys having somewhat higher levels than the girls. Use of oral contraceptives significantly increased the RBP level. The mean zinc values were rather constant throughout puberty, but boys 13-14 years of age had significantly depressed values. There was a statistically significant correlation between the serum levels of zinc and RBP.

Some aspects of the intestinal absorption of zinc in man.

Serum zinc concentrations in peripheral venous blood were determined in 8 healthy volunteers at various times after oral administration of 50 mg Zn++. The same dose was given to 6 patients surgically treated for obesity by jejuno-ileostomy. In the healthy volunteers the mean serum zinc concentration before dosing was 0.89 mug/ml and a mean peak concentration of 2.39 mug/ml was found after 3 h. In the patients the starting level was lower, 0.67 mug/ml, and a mean peak concentration of 1.31 mug/ml was found 90 min after treatment. In the patients the areas under the serum concentration-time curve was approximately 1/3 of that in the healthy subjects. Zn++ 50 mg was also given to 3 patients undergoing transumbilical catheterization of the portal vein for diagnostic purposes and serum zinc concentrations were measured in portal and peripheral venous blood sampled simultaneously. No significant differences were found between the concentration of zinc in portal and peripheral venous blood during absorption, which suggests slow passage of zinc across the intestinal wall.