Health-related quality of life in patients with metastatic renal cell carcinoma treated with sunitinib vs interferon-�� in a phase III trial: final results and geographical analysis

Background:

In a randomised phase III trial, sunitinib significantly improved efficacy over interferon-α (IFN-α) as first-line therapy for metastatic renal cell carcinoma (mRCC). We report the final health-related quality of life (HRQoL) results.

Methods:

Patients (n=750) received oral sunitinib 50 mg per day in 6-week cycles (4 weeks on, 2 weeks off treatment) or subcutaneous IFN-α 9 million units three times weekly. Health-related quality of life was assessed with nine end points: the Functional Assessment of Cancer Therapy–General and its four subscales, FACT–Kidney Symptom Index (FKSI-15) and its Disease-Related Symptoms subscale (FKSI-DRS), and EQ-5D questionnaire''s EQ-5D Index and visual analogue scale. Data were analysed using mixed-effects model (MM), supplemented with pattern-mixture models (PMM), for the total sample and the US and European Union (EU) subgroups.

Results:

Patients receiving sunitinib reported better scores in the primary end point, FKSI-DRS, across all patient populations (P<0.05), and in nine, five, and six end points in the total sample, in the US and EU groups respectively (P<0.05). There were no significant differences between the US and EU groups for all end points with the exception of the FKSI item ‘I am bothered by side effects of treatment'' (P=0.02). In general, MM and PMM results were similar.

Conclusion:

Patients treated with sunitinib in this study had improved HRQoL, compared with patients treated with IFN-α. Treatment differences within the US cohort did not differ from those within the EU cohort.     

Synergistic effect of growth hormone-releasing hormone (GHRH) and clonidine in stimulating GH release in young and old dogs

The effect of acute administration of growth hormone-releasing hormone (GHRH), clonidine (CLO), an alleged GHRH releaser, or GHRH and clonidine given simultaneously was studied in young and old dogs. Simultaneous administration of CLO induced in young dogs an additive effect on GH release and potentiated in old dogs the GHRH-induced GH release, with the GH response being clearly higher than the sum of the GH responses to GHRH or CLO alone. These data suggest that CLO promotes GH release in the dog also by inhibition of somatostatin release.     

Behavioral weight control for overweight adolescents initiated in primary care.

OBJECTIVE: This study evaluates the post-treatment and short-term follow-up efficacy of, as well as participant satisfaction for, a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact. RESEARCH METHODS AND PROCEDURES: 44 overweight adolescents were randomly assigned to either a multiple component behavioral weight control intervention (Healthy Habits [HH]; n = 23) or a single session of physician weight counseling (typical care [TC]; n = 21). Weight, height, dietary intake, physical activity, sedentary behavior, and problematic weight-related and eating behaviors and beliefs were assessed before treatment, after the 4-month treatment, and at 3-month follow-up. Participant satisfaction and behavioral skills use were measured. RESULTS: HH adolescents evidenced better change in body mass index z scores to post-treatment than TC adolescents. Body mass index z scores changed similarly in the conditions from post-treatment through follow-up. Behavioral skills use was higher among HH than TC adolescents, and higher behavioral skills use was related to better weight outcome. Energy intake, percentage of calories from fat, physical activity, sedentary behavior, and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition. The behavioral intervention evidenced good feasibility and participant satisfaction. DISCUSSION: A telephone- and mail-based behavioral intervention initiated in primary care resulted in better weight control efficacy relative to care typically provided to overweight adolescents. Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth.     

Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis

Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r=-0.35; 95% confidence interval [CI]: -0.44 to -0.27), where each 100 micromol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r=0.34; 95% CI: -0.42 to -0.25), where each 100 micromol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.