Hormonal prostate cancer therapies and cardiovascular disease: a systematic review.

Therapeutic intervention for prostate cancer mostly relies on eliminating circulating androgen or antagonizing its effect at the cellular level. As the use of endocrine therapies grows, an under-reported incidence of cardiovascular toxicities occurs in prostate cancer patients. In this review, we summarize data of clinical studies, investigating the cardiovascular and metabolic alterations associated with the use of old and new endocrine drugs (gonadotropin-releasing hormone [GnRH] agonists and antagonists, androgen receptor inhibitors, 17α-hydroxylase/c-17,20-lyase [CYP17] inhibitor) in prostate cancer. To date, studies looking for links between cardiovascular complications and hormone-mediated therapies in prostate cancer have reached conflicting results. Several confounding factors, such as age of patients and related cardiovascular liability, other comorbidities, and use of concomitant drugs, have to be carefully evaluated in future clinical trials. Further research is needed given the continuous advancements being made in prostate cancer treatment.

[Analysis of the European Consensus on the treatment of opioid-induced constipation analgesic drugs.] / Analisi del consensus europeo sul trattamento della stipsi indotta da farmaci analgesici oppiacei.

Until recently, conclusive data on clinical presentation, diagnosis and therapy of the opioid-induced constipation (OIC) were not available. Lately, some phase II and III prospective studies, evaluating the efficay of several old and new laxatives in cancer and non-cancer patients, make their mechanisms of action easier to understand and lead healthcare institutions to determine homogeneous guidelines for OIC, with the use of diagnostic and treatment algorithms. On May 2018, management recommendations from a panel of 7 European experts on OIC was published on United European Gastroenterology Journal. They discussed on different aspects of OIC: (a) definitions and diagnostic criteria; (b) pathophysiology; (c) clinical evaluation; (d) patient reported outcome measures; (e) initial standard laxatives; (f) specific treatments; (g) pragmatic recommendations. Later, a multi-disciplinary panel consisting of experts in neurogastroenterology, oncology and palliative medicine gave their external input. This statement will help clinicians to harmoniously treat OIC, according to clear guidelines, resulted from phase II and III prospective studies. Nevertheless, the constipation is rarely due to opioids consumption alone. More often, different factors contribute to induce constipation, including diet, immobility, other drugs, pain during evacuation, comorbidities, gastrointestinal obstacles, especially in advanced cancer patients. Therefore, management of OIC always needs to be tailored to the individual patient based on their overall clinical picture.

Chemotherapy in Patients with Hereditary Angioedema.

BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant hereditary disorder characterized by episodic swelling of many body regions (especially throat and abdomen), potentially triggered by medication. No data are available for HAE in patients with cancer assigned to standard chemotherapy. The aim of our study was to identify circulating mediators potentially predictive of acute HAE attacks during chemotherapy. PATIENT AND METHODS: Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers and for routine haematochemistry were performed in a 42-year-old male affected by type 2 HAE during standard adjuvant oxaliplatin/fluorouracil-based chemotherapy administered for stage III radically resected rectal cancer. Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment. Mann-Whitney U-test was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy. RESULTS: Pre-chemotherapy values of tested variables (day 0) were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml. A significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional. Four HAE attacks were observed, they started from the forth cycle of treatment and all were manageable. Changes in C3, D-dimers and C1-inhibitor functional preceded the attacks. CONCLUSION: The stress induced by chemotherapy such a standard oxaliplatin/fluorouracil increases the risk of attacks in patients with HAE. However, circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional may serve as early predictors of acute HAE crisis.

Kallikrein-related peptidases targeted therapies in prostate cancer: perspectives and challenges.

INTRODUCTION: Despite the emergence of several new effective treatments for metastatic castration-resistant prostate cancer patients, disease progression inevitably occurs, leading scientific community to carefully look for novel therapeutic targets of prostate cancer. Kallikrein (KLK)-related peptidases have been demonstrated to facilitate prostate tumorigenesis and disease progression through the development of an oncogenic microenvironment for prostate cells. AREAS COVERED: This review first summarizes the large amount of preclinical data showing the involvement of KLKs in prostate cancer pathobiology. In the second part, the authors assess the current status and future directions for KLK-targeted therapy and briefly describe the advances and challenges implicated in the design of effective manufactured drugs. The authors then focus on the preclinical data and on Phase I/II studies of the most promising KLK-targeted agents in prostate cancer. The drugs discussed here are divided on the basis of their mechanism of action: KLK-engineered inhibitors; KLK-activated pro-drugs; KLK-targeted microRNAs and small interfering RNAs(-/)small hairpin RNAs; KLK vaccines and antibodies. EXPERT OPINION: Targeting KLK expression and/or activity could be a promising direction in prostate cancer treatment. Future human clinical trials will help us to evaluate the real benefits, toxicities and the consequent optimal use of KLK-targeted drugs, as mono-therapy or in combination regimens.

Over 17-month complete clinical brain response with a well-tolerated lapatinib plus capecitabine combination in a very young patient afflicted by HER2-positive metastatic breast cancer.

This report describes a case of ab initio metastatic HER2-positive breast cancer in a very young patient. The onset of breast cancer at such a young age is uncommon and could delay the diagnosis with unquestionable impact on the prognosis. Unfortunately, the patient experienced cerebral progression during first-line treatment. Indeed, brain metastases occur in about one-third of HER2-positive metastatic breast cancer patients during trastuzumab-based treatment. The small molecule lapatinib is active in established cerebral disease, and we report a complete brain response longer than expected, thanks to a well-tolerated, orally administered combination of lapatinib and capecitabine.

Metastasis to the Pancreas from Breast Cancer: Difficulties in Diagnosis and Controversies in Treatment.

BACKGROUND: Metastasis to the pancreas originating from malignant tumours is a rare event and, in the literature, we have found only 11 reported cases of solitary pancreatic metastases originating from breast cancer. CASE REPORT: We report a case of a 51-year-old woman with primary breast cancer who developed obstructive jaundice and epigastric pain after 2 years without any symptoms. The pancreatic mass revealed by computed tomography (CT) scan and magnetic resonance imaging (MRI) was not recognised as a metastasis from breast cancer and the patient underwent cephalic pancreaticoduodenectomy. CONCLUSIONS: We discuss all aspects of the case management, stressing the importance of a careful evaluation of the clinical history and the primary cancer features and the usefulness of a multi-disciplinary approach. These aspects are of main importance for a correct diagnostic process and an appropriate therapeutic choice when a pancreatic lesion develops in a patient with prior neoplasm.