Bisphosphonates in patients with renal cell carcinoma and bone metastases: a sunitinib global expanded-access trial subanalysis.

AIM: To investigate retrospectively the effects of bone metastases and bisphosphonates in sunitinib-treated metastatic renal cell carcinoma patients. PATIENTS & METHODS: Patients in Groups (Gp) 1 and 2, but not Gp3, had bone metastases. Gp2 received bisphosphonates following standard practice. RESULTS: Gp2 had less favorable prognosis than Gp1. Gp3 had fewer metastases and the best prognosis. More serious adverse events occurred in Gp2 versus Gp1. The difference in overall survival between Gp1 and Gp2 was not significant after adjusting for covariates. Significantly shorter overall survival in Gp1 versus Gp3 persisted after adjusting for covariates. CONCLUSION: Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

Central and Eastern European experience with sunitinib in metastatic renal cell carcinoma: a sub-analysis of the global expanded-access trial.

A global, open-label, expanded-access trial (EAT) provided sunitinib treatment on a compassionate-use basis to patients with metastatic renal cell carcinoma (mRCC) between 2005 and 2011. This retrospective analysis examines outcomes in patients from Central and East European (CEE) countries participating in the global EAT. Sunitinib (starting dose 50 mg orally once daily, with dose reduction for toxicity) was administered in repeated 6-week cycles (4 weeks on and 2 weeks off) until occurrence of disease progression or unacceptable toxicity. Tumor assessments were guided by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but were performed according to local standards of care. In total, 401 CEE patients received sunitinib (median treatment duration 9.6 months), of whom 378 were evaluable for tumor response. The most frequent grade ≥3 toxicities were fatigue (7.5 %), hypertension (7.0 %), thrombocytopenia (6.5 %), diarrhea (4.2 %), nausea and hand-foot syndrome (both 3.7 %) and neutropenia (3.0 %). Median overall survival was 30.7 months (95 % CI 23.3, ‒ months). Overall survival tended to be longer in cytokine-naïve than cytokine-experienced patients (median 60.8 vs. 27.5 months; P = 0.1324). Among patients with evaluable tumors, 4.0 % achieved a complete and 14.6 % a partial response [objective response rate (ORR) 18.5 % (95 % CI 14.7, 22.8 %)]. Median progression-free survival was 11.6 months (95 % CI 10.3, 12.8 months). Sunitinib demonstrates safety and effectiveness in real-world mRCC patients in CEE countries. Expanded-access program patients showed a lower tumor response rate but similar survival outcomes to patients in the pivotal Phase III clinical trial of sunitinib in mRCC.

Objective: remission of depression in primary care The Oreon Study.

OBJECTIVE: Treatment of depression should result in the absence of symptoms, i.e. remission, in order to restore the functional status of the patient and reduce the risk for relapse. The study assessed the current remission rates in primary care and determined the influencing factors. METHODS: 10 consecutive depressive patients treated by antidepressants for at least 3 months and not more than 12 months were screened by each investigator. Remission rates were defined using the Hamilton-Depression scale 7 items (score of 3 or less) as well as the Carroll self rating scale (score of 7 or less). In addition, patients completed the Sheehan Disability Scale (SDS). Initial severity of depression, type of treatment and socio-economic factors were collected. RESULTS: 292 general practitioners screened a total of 2630 patients. Results indicated low remission rates: 28.3% according to the clinician and 17.1% according to the patient. Absence of remission was associated with higher impairment in work, social and family life. The most frequently reported residual symptoms in nonremitters were general somatic symptoms (92%), depressed mood (92%), psychic anxiety (91%) and impaired work and activities (89%). No differences were observed in remission rates between men and women. Remission rates were significantly lower in patients living alone as compared to those living in couple or family (25.1% vs 30.2%, p=0.03), in patients with lower education (21.3% vs 32.3%, p<0.001), in patients speaking French as compared to Dutch (24.0% vs 34.0% p<0.001), and unemployed patients compared to patients having an occupation (17.1% vs 39.0%, p<0.001). Higher initial severity and number of previous episodes decreased remission rates (p<0.001). CONCLUSION: This study shows low remission rates in depressed patients treated in general practice. The absence of remission is associated with impairment in work, social and family life. Special attention should be given to identify patients who do not reach remission.

Socioeconomic correlates of generalized anxiety disorder and major depression in primary care: the GADIS II study (Generalized Anxiety and Depression Impact Survey II).

A previous Generalized Anxiety Disorder Impact Survey (GADIS I) performed on 15,399 Belgian patients consulting their primary care physicians, revealed high prevalences of generalized anxiety disorder (GAD) and major depression (MD) with important regional differences. The objective of this study (GADIS II) was to replicate previous findings and to evaluate the role of socioeconomic factors in the diagnoses of GAD and MD. A large-scale cross-sectional survey was conducted in a random sample of 377 general practitioners distributed geographically over Belgium and Luxemburg. Each physician was asked to screen 40 consecutive patients at predefined time periods for the presence of GAD and MD using sections of the Mini International Neuropsychiatric Interview (MINI). Socioeconomic parameters were collected. The level of impairment was assessed using the Sheehan Disability Scale. In a sample of 13,699 patients, point prevalences of GAD and of MD were found to be 13.4 and 11.0%, respectively. Overall, 17.8% of the population was positive for GAD and/or MD. Both disorders were significantly more frequent in women than in men. Marked regional differences were observed with prevalences for GAD and/or MD of 24.2% in Brussels, 22.7% in Wallonia, 13.6% in Luxemburg and 12.9% in Flanders. Several socioeconomic factors were significantly associated with positive diagnoses: living alone, a low level of education and unemployment. However, regional differences remained significant even after controlling for socioeconomic factors. The study confirms the high prevalence of GAD and MD in primary care and the role of several socioeconomic and regional factors in the illnesses.

Prevalence and impact of generalized anxiety disorder and major depression in primary care in Belgium and Luxemburg: the GADIS study.

PURPOSE: GADIS aims at determining the prevalence of generalized anxiety disorder (GAD) and major depression (MD) in primary care and their impact on the patient's functioning in Belgium and Luxemburg. METHOD: A large scale screening program was conducted at the consultation of general practitioners to detect patients with GAD and MD according to DSM-IV criteria. We collected additional data regarding the use of hypnotic, tranquilizer, antidepressant and analgesic medications. Impact on the patient was assessed with the Sheehan disability scale. RESULTS: Three hundred GP's in Belgium and Luxemburg were asked to screen 50 consecutive patients. Of the 13,677 analyzed patients, 8.3% were diagnosed to have GAD and 6.3% MD. Comorbidity was observed in 4.2% of patients. The prevalence was much higher in the French-speaking part of Belgium. GAD and MD were associated with impairment in social, familial and professional functioning. Only a minority of patients with GAD and/or MD was treated with an antidepressant and almost half of subjects with GAD and/or MD were treated with a tranquilizer. CONCLUSION: Prevalence rates of GAD and MD in primary care in Belgium are comparable to other countries. GAD and MD are disabling conditions. Antidepressants are still used only in a minority of subjects with GAD and/or MD in primary care in Belgium and Luxemburg. The prevalence of GAD and MD appears to be much higher in French-speaking parts of Belgium.

Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety.

The aim of this double-blind study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of patients with depression and anxiety. A total of 146 moderately depressed patients with associated anxiety were randomized to receive 75 mg/d venlafaxine or 20 mg/d fluoxetine for 12 wk. Dose increases were permitted after 2 wk of treatment, to 150 mg/d venlafaxine and 40 mg/d fluoxetine, to optimize response. At the final visit, a statistically significantly greater efficacy of venlafaxine over fluoxetine was observed on depressive symptoms and concomitant anxiety, and 75.0 and 50.7% of patients administered venlafaxine and fluoxetine, respectively, showed an overall response. A sustained response (for at least 2 wk), present at the end of the study was achieved in 57.8 and 43.3% of patients in the venlafaxine and fluoxetine groups, respectively, and at the final visit, 59.4 and 40.3% of patients, respectively, were in remission (virtually asymptomatic). Dose increases were required by a greater percentage of patients in the fluoxetine group (52.9%), than in the venlafaxine group (37.1%), and in those patients whose dose was increased, a higher efficacy was again observed with venlafaxine. Venlafaxine and fluoxetine were well tolerated, with the most frequently experienced adverse events being nausea and headache. Fewer patients in the venlafaxine group than in the fluoxetine group reported at least one adverse event (55.7 and 67.1% patients, respectively). Venlafaxine therefore proved to be significantly more effective than fluoxetine in improving depressive symptoms and concomitant anxiety.