Central nervous system metastases from castration-resistant prostate cancer in the docetaxel era.

Central nervous system (brain or leptomeningeal) metastases (BLm) are considered rare in castration-resistant prostate cancer (CRPC) patients. Now that docetaxel has become the reference drug for first-line treatment of CRPC, patients whose disease is not controlled by hormonal manipulations may live much longer than before and have higher risk of developing BLm. We retrospectively reviewed the records of all patients with CRPC attending our centres from 2002 to 2010, and identified all of those who were diagnosed as having BLm and received (or were considered to have been eligible to receive) docetaxel-based treatment. We identified 31 cases of BLm (22 brain metastases and 9 leptomeningeal metastases) with an incidence of 3.3%. BLm-free survival was 43.5 months, and survival after BLm discovery was 4 months. With six patients surviving for more than 1 year after developing BLm, the projected 1-year BL-S rate was 25.8%. The findings of our study may be relevant in clinical practice as they indicate that incidence of BLm in CRPC patients in the docetaxel era seems to be higher than in historical reports, meaning that special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors because they may be related to BLm

Type 1 diabetes, diabetic nephropathy, and pregnancy: a systematic review and meta-study

BACKGROUND: In the last decade, significant improvements have been achieved in maternal-fetal and diabetic care which make pregnancy possible in an increasing number of type 1 diabetic women with end-organ damage. Optimal counseling is important to make the advancements available to the relevant patients and to ensure the safety of mother and child. A systematic review will help to provide a survey of the available methods and to promote optimal counseling. OBJECTIVES: To review the literature on diabetic nephropathy and pregnancy in type 1 diabetes. METHODS: Medline, Embase, and the Cochrane Library were scanned in November 2012 (MESH, Emtree, and free terms on pregnancy and diabetic nephropathy). Studies were selected that report on pregnancy outcomes in type 1 diabetic patients with diabetic nephropathy in 1980-2012 (i.e. since the detection of microalbuminuria). Case reports with less than 5 cases and reports on kidney grafts were excluded. Paper selection and data extraction were performed in duplicate and matched for consistency. As the relevant reports were highly heterogeneous, we decided to perform a narrative review, with discussions oriented towards the period of publication. RESULTS: Of the 1058 references considered, 34 fulfilled the selection criteria, and one was added from reference lists. The number of cases considered in the reports, which generally involved single-center studies, ranged from 5 to 311. The following issues were significant: (i) the evidence is scattered over many reports of differing format and involving small series (only 2 included over 100 patients), (ii) definitions are non-homogeneous, (iii) risks for pregnancy-related adverse events are increased (preterm delivery, caesarean section, perinatal death, and stillbirth) and do not substantially change over time, except for stillbirth (from over 10% to about 5%), (iv) the increase in risks with nephropathy progression needs confirmation in large homogeneous series, (v) the newly reported increase in malformations in diabetic nephropathy underlines the need for further studies. CONCLUSIONS: The heterogeneous evidence from studies on diabetic nephropathy in pregnancy emphasizes the need for further perspective studies on this issue

Intermittent docetaxel chemotherapy as first-line treatment for metastatic castration-resistant prostate cancer patients

Aims: The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. Patients & methods: All patients received DOC 70 mg/m every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. Results: The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. Conclusion: Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL

GU-CA-COVID: a clinical audit among Italian genitourinary oncologists during the first COVID-19 outbreak

Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design, setting, and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population

Long-term use of sorafenib (SOR) in metastatic renal cell carcinoma (mRCC) previously treated with systemic therapy

Background: The recent development of new targeted agents for the treatment of advanced RCC has definitely changed the approach and the outcome of this disease. Among them, SOR, has proved to be highly active in the treatment of mRCC. The aim of this study was to assess the activity and the safety of SOR in pts with mRCC relapsed after prior systemic therapy. Methods: Between 2/2007 and 10/2008, 22 pts with mRCC relapsed after 1–2 prior lines of chemotherapy (gemcitabine, vinorelbine, 5-FU) have been treated with SOR orally administered at the dose of 400mg b.i.d. continuous dosing. They were18 males and 4 females, with a median age 67 years, an ECOG PS 0–2, and the majority (96%) had undergone prior nephrectomy. Patients were assessed for activity every three months (mos.) by CT. The primary endpoints were response rate (RR) evaluated by RECIST criteria and time to progression (TTP). Results: To date, 20 pts are evaluable for response: of them, 13 (59%) achieved a partial response (PR) after 3 mos. of therapy whose median duration was 13 mos. (range, 7–18), while 7 (31%) remained with stable disease (SD) with a median length of 14 mos. (range, 5–17). No complete responses have been observed. Among those who progressed (2 pts), the median time to disease progression was 7 mos. At a median length of time of 15 mos., 18 pts. are continuing the therapy with SOR and in all of them the benefit achieved remained unchanged. Two pts discontinued the treatment because of the onset of side effects, while in 4 pts dose reductions were required. Grade 3/4 toxicities were: hypertension in 3 pts (13%), hand-foot skin reactions in 5 (22%), rash/desquamation in 4 (18%), diarrhoea in 2 (9%), fatigue in 6 (27%), bleeding in 2 (9%). Conclusions: These data confirm other experiences showing the efficacy of SOR in previously treated patients with mRCC. However, notwithstanding the rather small sample size of pts., the overall clinical benefit rate (PR+SD) turned out particularly high (> 90%): chiefly, the evidence of a long lasting disease control both for patients achieving partial response and for those with stable disease makes SOR a very useful treatment for patients with mRCC

Playing the devil’s advocate: Should we give a second chance to mTOR inhibition in renal clear cell carcinoma? – ie strategies to revert resistance to mtor inhibitors

In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician’s expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combina-tions of mTOR inhibitors and other anti-cancer drugs