Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the safety and efficacy of cabozantinib combined with docetaxel. PATIENTS AND METHODS: This was a phase 1/2 multicentre study in patients with metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (75 mg/m2 every 3 weeks with daily prednisone 10 mg) was combined with escalating doses of daily cabozantinib (20, 40 and 60 mg). Based on the results of the phase 1 study, the investigation was expanded into a randomized study of docetaxel with prednisone (hereafter 'docetaxel/prednisone') plus the maximum tolerated dose (MTD) of cabozantinib compared with docetaxel/prednisone alone. RESULTS: A total of 44 men with mCRPC were enrolled in this phase 1/2 trial. An MTD of 40 mg cabozantinib plus docetaxel/prednisone was determined. Dose-limiting toxicities were neutropenic fever and palmar-plantar erythrodysesthesia, and there was one death attributable to a thromboembolic event. In addition, grade 3 or 4 myelosuppression, hypophosphataemia and neuropathy were seen in three or more patients. In the phase 1 study, the median time to progression (TTP) and overall survival (OS) time were 13.6 and 16.3 months, respectively. In the phase 2 study, which was terminated early because of poor accrual, the median TTP and OS favoured the combination (n = 13) compared to docetaxel/prednisone alone (n = 12; 21.0 vs 6.6 months; P = 0.035 and 23.8 vs 15.6 months; P = 0.072, respectively). CONCLUSION: Despite the limited number of patients in this study, preliminary data suggest that cabozantinib can be safely added to docetaxel/prednisone with possible enhanced efficacy.

Intensifying the Hormonal and Radiation Treatment in Prostate Cancer Presenting With Bulky Pelvic Lymph Nodes: An Opportunity for a New Paradigm.

Locally advanced prostate cancer may rarely present with bulky pelvic lymph nodes without distant metastasis. Patients may be treated with curative intent. Dual hormonal therapy including luteinizing hormone-releasing hormone agonist in combination with abiraterone or enzalutamide can be utilized neoadjuvantly to shrink bulky disease. This can be followed by radical doses of radiotherapy. This intensified treatment is tolerable. Prostate-specific membrane antigen scan can be utilized to assess staging and treatment response. Here, we present a case of a non-metastatic locally advanced prostate cancer with bulky pelvic lymph nodes. The patient was treated neoadjuvantly with dual hormonal therapy followed by radical doses of radiotherapy. The patient tolerated the treatment well and had a promising early response.

Bleomycin and perioperative care: a case report.

 Bleomycin is associated with pulmonary toxicity ranging from pneumonitis, pulmonary fibrosis, to fatal acute respiratory distress syndrome. Oxygen administration can potentiate or precipitate bleomycin pulmonary toxicity, and the most common setting of oxygen exposure is during anesthesia. We report here the successful management and perioperative care of a patient with documented bleomycin pulmonary toxicity who had to undergo an eight hour long retroperitoneal surgery. With proper preoperative assessment, chest physiotherapy, inhaled steroids and bronchodilators, antibiotics, operative restriction of oxygen and fluids and good postoperative care no further pulmonary insult was inflicted.

Deciphering Urogenital Cancers through Proteomic Biomarkers: A Systematic Review and Meta-Analysis.

Urogenital cancers, which include prostate, bladder, and kidney malignancies, exert a substantial impact on global cancer-related morbidity and mortality. Proteomic biomarkers, emerging as valuable tools, aim to enhance early detection, prognostic accuracy, and the development of personalized therapeutic strategies. This study undertook a comprehensive systematic review and meta-analysis of the existing literature investigating the role and potential of proteomic biomarkers in plasma, tissue, and urine samples in urogenital cancers. Our extensive search across several databases identified 1879 differentially expressed proteins from 37 studies, signifying their potential as unique biomarkers for these cancers. A meta-analysis of the significantly differentially expressed proteins was executed, accentuating the findings through visually intuitive volcano plots. A functional enrichment analysis unveiled their significant involvement in diverse biological processes, including signal transduction, immune response, cell communication, and cell growth. A pathway analysis highlighted the participation of key pathways such as the nectin adhesion pathway, TRAIL signaling pathway, and integrin signaling pathways. These findings not only pave the way for future investigations into early detection and targeted therapeutic approaches but also underscore the fundamental role of proteomics in advancing our understanding of the molecular mechanisms underpinning urogenital cancer pathogenesis. Ultimately, these findings hold remarkable potential to significantly enhance patient care and improve clinical outcomes.

Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer.

BACKGROUND: The standard treatment for non-metastatic castration sensitive prostate cancer (nmCSPC) is androgen deprivation therapy (ADT) or surveillance. This study evaluated the potential synergy of immunotherapy and enzalutamide (without ADT) in nmCSPC. In addition, the immunologic impact of enzalutamide was also evaluated in men with normal testosterone. METHODS: Patients with rising prostate-specific antigen (PSA) after definitive therapy, normal testosterone and no radiographic metastasis were randomized to enzalutamide for 3 months with/without PROSTVAC for 6 months. Thereafter, patients could be retreated with another 3 month course of enzalutamide when PSA returned to baseline. Immune profiles were evaluated in these patients. RESULTS: Thirty-eight patients were randomized with a median PSA=4.38 ng/dL and PSA doubling time=4.1 months. No difference was observed between the two groups for PSA growth kinetics, but PSA responses to enzalutamide were noteworthy regardless of PROSTVAC. The median PSA decline after short-course enzalutamide without ADT/testosterone lowering therapy was 99% in both courses. The median time to PSA recovery to baseline after each 84-day course of enzalutamide was also noteworthy because of the duration of response after enzalutamide was discontinued. After the first and second 3 month cycle of enzalutamide, PSA recovery to baseline took a median 224 (range 84-1246) and 189 days (78-400), respectively. The most common adverse events related to the enzalutamide were grade 1 fatigue (71%) and grade 1 breast pain/nipple tenderness (81%). The only grade 3 toxicity was aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation in two patients. Enzalutamide was independently associated with immune changes, increasing natural killer cells, naïve-T cells, and decreasing myeloid-derived suppressor cells. CONCLUSIONS: Three months of enzalutamide without ADT induced substantial PSA control beyond the treatment period and was repeatable, perhaps representing an alternative to intermittent ADT in nmCSPC. In addition, enzalutamide was associated with immune changes that could be relevant as future immune combinations are developed. TRAIL REGISTRATION NUMBER: clinicaltrials.gov (NCT01875250).

The changing landscape of systemic therapy in metastatic renal cell carcinoma: an update.

Treatment options for metastatic renal cell carcinoma (RCC) continue to expand. Three recent phase III trials, Checkmate 214, Keynote-426, and Javelin Renal 101, have led to FDA approval of three new regimens for patients with clear cell RCC: nivolumab plus ipilimumab, pembrolizumab plus axitinib, and avelumab plus axitinib, respectively. At the same time, the dearth of treatment options for non-clear cell RCC has changed very little. The role of cytoreductive nephrectomy has also come into question after the publication of the CARMENA and SURTIME trials. This review will examine recent changes in therapeutic options in clear cell RCC and non-clear RCC, and the role of surgery in the treatment of metastatic RCC.

Novel immunotherapy combinations for genitourinary cancers.

Introduction: Several immune checkpoint inhibitors are FDA-approved for metastatic/advanced RCC and urothelial carcinoma (UC) based on improvements in survival. The dendritic cell vaccine, sipuleucel-T, is also approved for patients with mCRPC, based on a 4-month survival benefit.Areas covered: Preclinical evidence suggests that there is promise in combining immune checkpoint inhibitors with several different classes of anti-cancer agents, including tumor-directed vaccines, cytokines, chemotherapy, and multi-targeted tyrosine kinase inhibitors. Here we review immunotherapy combinations currently approved for RCC, UC, and prostate cancer with a focus on emerging therapies. We conducted a search of peer-reviewed publications and recent meeting abstracts and provide an overview of ongoing combination immunotherapy trials for genitourinary malignancies and discussion of preliminary findings where available.Expert opinion: Recently, many potential immunotherapy combinations have emerged. In addition to determining clinical activity, important challenges include investigating additive adverse effects and determining the best sequence of therapy.

Diagnostic overlap of depressive, anxiety, stress and somatoform disorders in primary care.

INTRODUCTION: The aim of the present study was to determine the prevalence of somatization, anxiety, depression and stress in a primary care population, explore their association to psychosocial stressors and determine the diagnostic overlap of these four mental disorders. METHODS: This is a prospective cross-sectional study. A representative sample of 2,150 patients was approached, of whom 1,762 patients agreed to participate and responded to the questionnaire (81.9%). Anxiety was assessed with the Generalized Anxiety Disorder Scale (GAD-7). Depression was assessed with the depression module Patients Health Questionnaire-8. Somatization was measured with the somatic symptom module PHQ-15. The Perceived Stress Scale (PSS) instrument was used to identify the stress cases. RESULTS: Of the study sample, 23.8% of the total cases were identified as probable cases. The prevalence of somatization, depression, anxiety and stress was 11.7%, 11.3%, 8.3% and 18.6%, respectively. The specific gender prevalence of these four psychological disorders was very similar in men and women: depression (11.3% versus 11.3%), anxiety (7.7% versus 8.9%), somatization (12.5% versus 10.7%) and stress disorders (19.3% versus 17.8%). A significant difference was observed in nationality and marital status for depression and anxiety (P < 0.05). The age-specific prevalence rate showed a higher prevalence in the age group 45-54 years: depression (13.3%), anxiety (9.5%), somatization (12.8%) and stress (20.4%). Unable to control worries (69.2%) was the worst symptom for anxiety disorders, while the majority of the depressed patients wanted to hurt themselves (71.9%). Stomach pain (46.1%) was the most common symptom in somatic patients. Most of the patients experiencing stress could not cope with their daily duties (65.9%). There was a high comorbidity rate of depression, anxiety, somatization and stress observed in the studied population (9.3%). CONCLUSION: The prevalence of somatization and depression was similar, but the prevalence of stress was higher in inpatient patients. Somatization, depression, anxiety and stress disorders co-occurred at higher rate in the study sample.

Medical audit of the quality of diabetes care: is primary care more successful than hospitals?

OBJECTIVE: To assess the quality of diabetes care provided to patients attending primary care settings and hospitals in the State of Qatar. DESIGN: Observational cohort study. SETTING: The survey was carried out in primary health care centers and hospitals. SUBJECTS AND METHODS: The study was conducted from January 2010 to August 2010 among diabetic patients attending primary health care centers and hospitals. Among the patients participating, 575 were from hospitals and 1103 from primary health care centers. Face-to-face interviews were conducted using a structured questionnaire including sociodemographic, clinical, and satisfaction score of the patients. RESULTS: The mean age of the primary care diabetic patients was 46.1 ± 15.1 years and 44.5 ± 14.8 years for hospital patients (P = .03). There was a significant difference observed in terms of age group, gender, marital status, occupation, and consanguinity of the diabetic patients in both medical settings (P < .001). Overweight was less prevalent in primary care patients than in hospital diabetes mellitus patients (40.4% vs 46.4%). A significant variation was observed in the mean values of blood glucose (-0.76), HbA1C (-0.78), LDL (-0.01), albumin (-0.37), bilirubin (-0.76), and triglyceride (-0.01) in primary care patients compared to the mean values of the preceding year. Overall, complications were lower in primary care diabetic patients, and patients attending primary care were more satisfied with the diabetes care. CONCLUSION: The present study revealed that in general, primary health care provided a better quality of care to diabetic patients compared to that of hospitals. Also, primary care patients had a better satisfaction score towards diabetes care.

Does good clinical practice at the primary care improve the outcome care for diabetic patients? Gender differences.

BACKGROUND: The Middle East region is predicted to have one of the highest prevalence of diabetes mellitus (DM) in the world. This is the first study in the region to assess treatment outcome of DM according to gender. OBJECTIVE: To assess the quality and effectiveness of diabetes care provided to patients attending primary care settings according to gender in the State of Qatar. DESIGN: It is an observational cohort study. SETTING: The survey was carried out in primary health care (PHC) centers in the State of Qatar. SUBJECTS AND METHODS: The study was conducted from January 2010 to August 2010 among diabetic patients attending (PHC) centers. Of the 2334 registered with diagnosed diabetes, 1705 agreed and gave their consent to take part in this study, thus giving a response rate of 73.1%. Face to face interviews were conducted using a structured questionnaire including socio-demographic, clinical and satisfaction score of the patients. RESULTS: Majority of subjects were diagnosed with type 2 DM (84.9%). A significantly larger proportion of females with DM were divorced or widowed (9.1%) in comparison to males with DM (3.4%; p<0.001). A significantly larger proportion of females were overweight (46.5%; p=0.009) and obese (29.5%; p=0.003) in comparison to males. Males reported significantly greater improvements in mean values of blood glucose (mmol/l) (-2.11 vs. -0.66; p=0.007), HbA1c (%) (-1.44 vs. -0.25; p=0.006), cholesterol (mmol/l) (-0.16 vs. 0.12; p=0.053) and systolic blood pressure (mmHg) (-9.04 vs. -6.62; p<0.001) in comparison to females. While there was a remarkable increase in male patients with normal range of fasting blood glucose (FBG; 51.6%) as compared to the FBG measurement 1 year before (28.5%: p<0.001) there was only a slight increase in females normal range FBG during this period from 28.0% to 30.4% (p=0.357). CONCLUSION: The present study revealed that the current form of PHC centers afforded to diabetic patients provided significantly improved outcomes for males, but only minor improved outcomes for females. This study reinforces calls for a gender-specific approach to diabetes care.