Early use of abiraterone and radium-223 in metastatic prostate cancer

[No abstract available

Monocyte count is a thrombosis marker: a pilot study.

This prospective case-control study suggests that monocyte value is both an easy and useful thrombosis criterion: the value above 500 cells/mm3 correlates with thrombosis at the onset and the value below 400 cells/mm3 correlates with restoration of vessel patency; moreover this difference is similar as that observed with d-Dimer value. Also in cancer patients, the monocyte value is a specific marker of DVT/PE and correlates with restoration of vessel patency differently from d-Dimer value which is above the normal value because of cancer.  It is interesting to notice that the d-Dimer rate of change does not correlate proportionally with the restoration of the vessel patency. In addition to this, the d-Dimer mean values are affected by an high error. After checking equipment and procedures to eliminate any potential source of systematic error, measurements of d-Dimer were repeated on the same specimens. However, the great variability of the measured values did not change, suggesting that the d-Dimer does not correlate with the pathology. Further study should analyze a third variable, in conjunction with d-Dimer and monocytes. This third parameter should be a factor well recognized as independent from DTV/PE as much as possible. The variability of this third variable should be affected by variability as well as the d-Dimer

Effectiveness and Safety of Therapy with Vitamin K Antagonists in Italian Patients Aged 80 Years or Older: a Multicentre Retrospective Study Comparing the Zeus Algorithm with the PARMA Algorithm or Manual Therapy.

The use of oral anticoagulant therapy (OAT) has constantly increased in the prevention of thromboembolism, particularly in patients 80 years of age or older. The aim of this multicentre study was to evaluate the efficacy and safety of vitamin K antagonists (VKAs) in elderly patients managed with a computer dosing algorithm compared with a dosage decided by expert physicians. Nine Italian thrombosis centres utilising the Zeus dosing algorithm were involved. The before-after study enrolled patients managed firstly by medical staff (manual system) or with the PARMA algorithm for 12 months from July 2008 to June 2009 and then with the Zeus algorithm during the analogous period from 2010 to 2011. Of 7605 patients in the OAT maintenance phase, 2281 were older than 80 years (mean age 84.2 years). Data for these 2281 patients managed with both modalities were analysed. Of the 2281 patients 80 years of age or older, 1776 underwent OAT for atrial fibrillation (AF). Use of a dosing algorithm increased the OAT quality: time in therapeutic range (TTR) was significantly (p < 0.001) higher during the Zeus period than during the manual period (71.6 vs. 68.8 %). The TTR achieved with Zeus was similar to that obtained with the PARMA algorithm. In addition, patients managed with Zeus took a weekly drug dosage significantly (p < 0.01) lower than that both suggested by PARMA and prescribed by expert physicians, with a reduced number of adverse events. This study confirms that the effectiveness and safety of VKA therapy in patients 80 years of age or older increases with computer dosing algorithms

Response to cabozantinib in renal cell carcinoma with cardiac metastases

In metastatic renal cell carcinoma (mRCC) patients, cardiac metastases are a rare and often a post-mortem finding. Clinical manifestations of cardiac metastases have a late onset and include pericardial effusions, heart failure and embolic phenomena. Treatment of cardiac metastasis is not yet standardized, and few data are available about the efficacy of TKI on treatment of cardiac metastases in mRCC patients. In this report, we describe the case of a 66-year-old male who presented with mRCC with lung and cardiac metastases treated with cabozantinib, a multikinase inhibitor that was administered in second line after disease progression with sunitinib. To date, there are no data about the safety and efficacy of cabozantinib in mRCC with cardiac metastasis. In a real word analysis, cabozantinib demonstrated to be associated to a modest risk of developing left ventricular heart failure. It is unknown if this risk is higher in mRCC population with cardiac metastases. We report the first evidence of efficacy and safety of cabozantinib in cardiac mRCC patients, probably due to its specific inhibition of several molecular intracellular pathways. Additional molecular and clinical studies are needed before well tolerated and efficacy of cabozantinib treatment for these patients can be fully understood

Prognostic Role of Systemic Inflammatory Indexes in Germ Cell Tumors Treated With High-Dose Chemotherapy

High-dose chemotherapy (HDCT) has curative potential in relapsed/refractory germ cell tumors (GCT). Due to the complexity of this population and the toxicity of HDCT, we evaluated the association between blood-based systemic inflammatory indexes and the outcome of GCT patients undergoing salvage treatment with HDCT in order to define additional prognostic factors able to orient clinical decision. Baseline characteristics, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) of 62 patients undergoing HDCT for GCT were retrospectively collected. The aim is to evaluate the correlation between each inflammatory marker (NLR, PLR, and SII) and response to HDCT, overall survival (OS), and progression-free survival (PFS). Using the receiver operating curve to identify the best cutoff values, it was found that patients with GCT with NLR &gt;= 3.3 and SII &gt;= 844,000 had shorter PFS and inferior OS. In the multivariable analysis including inflammatory markers, the International Prognostic Factor Study Group (IPFSG) risk group, age, and previous line of treatment, NLR &gt;= 3.3 and SII &gt;= 844,000 were identified to be independently associated with shorter PFS and OS. Moreover, NLR, PLR, and SII significantly correlate with overall response to HDCT. Associating IPFSG prognostic score to inflammatory markers at baseline of HDCT may improve prognostic information and could help physicians to make more personalized treatment decisions

Immune Modulation in Prostate Cancer Patients Treated with Androgen Receptor (AR)-Targeted Therapy

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p= 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27,p= 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60,p= 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS)

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. Methods: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. Results: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. Conclusions: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients’ satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. Funding: Molteni Farmaceutici, Italy