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.

Towards the audit of geriatric day hospitals: a pilot project in west Surrey/north east Hampshire.

Following the recommendation of a report on the performance of two geriatric day hospitals (GDHs) in West Surrey and North East Hampshire District Health Authority in 1988, a pilot study was set up to assess the efficacy of a proposed form of audit involving multidisciplinary teams. An outcome measure which consisted of four different scales was developed and agreed upon by the multi-professional team. These scales were used to work out a composite index (Patient Achievement Inventory-PAI). In addition, a new data form was designed for collection of patient data. To carry out this prospective clinical audit, targets were agreed for each patient, and progress was measured against them. Sixty-one (61) patients were studied (30 and 31 per respective hospital). Data form completion was 90 per cent and 81 per cent respectively. The PAI index proved to be reliable (kappa index of agreement = 0.72), and useful as an outcome measure. However, because the PAI index is made up of ordinal scales, it can only be used to measure change within individuals, not between them. The outcome measures, data forms and the continuous audit of these two GDHs proved to be meaningful and acceptable in practice.

A study of intracellular orthophosphate concentration in human muscle and erythrocytes by 31P nuclear magnetic resonance spectroscopy and selective chemical assay.

In order to study the relationship between extracellular and intracellular concentrations of orthophosphate (Pi), phosphorus nuclear magnetic resonance spectra were recorded, at rest, from the flexor digitorum superficialis muscle of hypophosphataemic patients with vitamin D-resistant rickets, and patients with Paget's disease of bone before and after they had been made hyperphosphataemic by treatment with the drug ethylidene-1-hydroxy-1,1-bisphosphonate. Changes in intramuscular P1 were estimated from the ratio of the areas of the Pi to adenosine 5'-triphosphate peaks. Even though the plasma Pi concentration in these patients spanned a fourfold range (0.5-2.0 mmol/l) the corresponding intramuscular Pi concentration increased by only 70%. A similar effect was observed in erythrocytes, from patients with these disorders, which were incubated in autologous plasma at 37 degrees C, under an atmosphere of O2 + CO2 (95:5, v/v). However, chloride ions, which are transported passively across the cell membrane, showed no change in distribution between cells and plasma, indicating that there was no general effect on passive anion distribution. When erythrocytes from normal subjects were incubated in autologous plasma (1.0 mmol of Pi/l) and in plasma supplemented with Pi (2.3 mmol of Pi/l), the Pi concentration in the cells, at steady state, increased only from 0.57 to 0.78 mmol/l cells, suggesting that the effect was not an artifact of disease or drug therapy. It is concluded that, in human skeletal myocytes and erythrocytes, the percentage change in the concentration of cytoplasmic Pi is lower than that in plasma. This implies that these cells can buffer or regulate cytoplasmic Pi when the extracellular concentration is disturbed.

Facilitating comprehension of discharge medication in elderly patients.

Provision of adequate information is well established as an important determinant of patient compliance with taking medication. Elderly patients, who constitute a large proportion of patients discharged from hospital on medication, may be particularly at risk of unintentional noncompliance due to inadequate or forgotten information. This study demonstrates that counselling provided to the elderly by a clinical pharmacist significantly improved knowledge about medication and, therefore, the opportunity for compliance at home.

Low dose choline chloride in cerebellar degeneration.

Sixteen patients with cerebellar degeneration were treated with oral choline chloride for six weeks at doses of 3 and 6 g daily. Two patients improved with choline but another four improved with placebo. Choline chloride in a dose of 3-6 g daily is no better than placebo in improving ataxia due to cerebellar degeneration.

Diabetes mellitus with ketoacidosis presenting as Fournier's gangrene.

Two patients with Fournier's gangrene are described. In each case this was the presenting clinical feature of diabetes mellitus with ketoacidosis. Histological examination demonstrated that the probable cause was intravascular fibrin deposition. The association between diabetes mellitus and Fournier's gangrene is discussed.