Reviews on Recent Clinical Trials - Volume 11, Issue 1, 2016

Head and neck cancer is one of the most common malignancies. Currently, it has a poor prognosis and significant mortality as the majority of malignancies present in later stages. Early diagnosis affords early intervention and the best chance of cure. However, the current gold standard for diagnosis largely depends on histopathology via an invasive procedure, tissue biopsy. The processing of biopsy material also inevitably leads to diagnostic delay and the possibility of taking an unrepresentative sample. Recently, there has been significantly increasing interest in the use of spectroscopy (e.g., fluorescence, elastic scattering, and Raman spectroscopy) and other optical systems to provide an early, real-time, non-invasive, and in situ diagnosis. Such diagnosis is based on the fact that the optical spectrum derived from any tissue reveals information about the histological and biochemical characteristics of that tissue. These optical systems have not only a role in cancer detection but also in treatment through guided biopsy, surgical margin assessment, and the monitoring of therapeutic drugs. However, our literature search is limited only to clinical diagnosis and only to the clinical trials published within recent 15 years (in 2000-2014). In this review, we will discuss and summarize the progress and new findings from recent clinical trials using these optical systems in the diagnosis of head and neck cancer.

As a consequence of both traditional and non-traditional risk factors, cardiovascular disease is over-represented, and the leading cause of mortality, among patients with Chronic Kidney Disease (CKD). Whilst recommendations for reducing cardiovascular risk in the general population exist, their applicability to the CKD population is questionable due to the exclusion of CKD patients from the majority of contemporary cardiovascular interventional studies. The aim of this review is to critically evaluate the literature regarding pharmacologic cardiovascular interventions in patients with CKD, with an emphasis on studies published since our 2008 review. Interventions discussed include erythropoiesis-stimulating agents (TREAT, U.S. Normal Hematocrit, CHOIR, CREATE, Palmer meta-analysis); statins (SHARP, AURORA, PPP, 4D, ALERT); Fibrates (VA-HIT); Folic Acid (ASFAST, US FOLIC acid trial, HOST); Antihypertensive Agents, Including Angiotensin-Converting Enzyme Inhibitors, angiotensin-receptor blockers, Beta-blockers and Combination therapy (Cice et al, FOSDIAL, Agarwal et al, ONTARGET); sevelamer (DCOR); Cinacalcet (ADVANCE, EVOLVE, Cunningham meta-analysis); Anti-oxidants (SPACE, HOPE, ATIC); Aspirin (HOT study re-analysis); vitamin D analogues (PRIMO); and multidisciplinary intervention (LANDMARK). Unfortunately, there remains a paucity of evidence in this area and a large number of methodologically poor quality studies with negative results. It is possible that these interventions do not have the same positive effect in CKD patients due to differences in the pathogenesis driving cardiovascular disease burden, such as altered bone metabolism and calcific vascular disease. Further well-designed studies with appropriately selected study populations and patient level outcomes are required. Until such time, physicians must consider on an individual patient basis the appropriateness of these interventions.

Currently, few efficient therapies are available to battle pancreatic cancer. Mechanisms underlying this cancer are not well known and researchers are trying to identify new therapeutic targets. Here, we present a review of new treatments and their results in recent years.

Heart failure remains a widespread commonly encountered clinical condition. It is responsible for increased healthcare expenditure, driven by frequent and often prolonged hospital admissions associated with an increased mortality. A clinically useful classification of the syndrome is, patients with left ventricular systolic impairment (Heart Failure and reduced ejection fraction, HFREF) and patients with preserved left ventricular systolic function (HFPEF). The pharmacological treatment for patients with HFREF has evolved over the last twenty five years, focusing on modulation of the neurohormonal activation which represents a hallmark of this condition. This has led to the development of a stepwise treatment algorithm predominately based on inhibition of the renin angiotensin aldosterone pathway and counteracting sympathetic over-activation. In particular since the early trials in chronic heart failure (CHF) demonstrated a significant mortality benefit with ACE-inhibitors, subsequent studies have been conducted in conjunction with these drugs. The rationale being that it would be unethical to trial any new agent without the concomitant use of ACE-inhibitors. The recent publication of the PARADIGM -HF study has challenged this convention by trialling a novel pharmacological agent against an ACE-inhibitor in a landmark trial. The review sets out the current pharmacological treatment for patients with heart failure and discusses the recent findings with this novel class of medication.

Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials.

Background: Prognostic variables associated with outcome after curative (R0) Resection of Colorectal Cancer (CRC) liver metastases are paramount in identifying high-risk patients after surgery. The aim of this study was to identify risk factors related to Overall Survival (OS) after R0 resection of CRC liver metastases. Methods: A literature search on prognostic factors after resection of liver metastases was performed. Studies were eligible if covariates associated with OS were reported in patients with R0 resected CRC liver metastases. Independent prognostic factors associated with OS were identified using multivariate analysis. Results: Twenty-four publications with a total of 4855 patients were eligible. In multivariate analyses, a disease-free interval < 12 months (hazard ratio [HR] 1.47, P = 0.0002), the size of the largest metastasis (HR 1.56, P < 0.0001), the total number of metastases (HR 1.73, P < 0.00001), a primary tumor with node-positive status (HR 1.56, P = 0.002), a rectal primary tumor (HR 1.48, P < 0.00001), a high carcinoembryonic antigen level (HR 1.49, P = 0.02), a high tumor grade (HR 2.42, P < 0.00001), and extrahepatic disease (HR 2.03, P < 0.00001) were associated with an increased risk of death after R0 resection of CRC liver metastases in at least 3 studies. Conclusion: We identified 9 clinicopathological prognostic factors that could help identify high-risk patients and guide further treatment and follow up decisions. In particular burden of liver and extrahepatic metastases and grade are those associated with a higher risk of death.

Background: To assess the role of early palliative care in patients with advanced oncologic and non-oncologic chronic diseases. Methods: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing early, simultaneous palliative care and standard care in patients with advanced oncologic and non-oncologic diseases were considered eligible and included into the analysis. The outcomes were classified into 6 classes: quality of life, symptoms control, overall survival, quality of care, patients’ and caregivers’ satisfaction, and costs of the assistance. Results: Twelve papers reporting the data of 9 trials were considered eligible and included into the analysis. Two nonrandomized trials were also included into the selection because of the methods used by the authors. The early, simultaneous approach was reported to improve quality of life in two out of 7 papers, symptoms control in 1 out of 5 papers, overall survival in 2 out of 3 papers, quality of care in 5 out of 8 papers, patients’ or caregivers’ satisfaction in 3 out of 4 papers; and to reduce the costs of assistance in 2 out of 3 papers. Conclusion: Early palliative care improves the main outcomes of the assistance in patients with advanced oncologic and non-oncologic chronic diseases. The available data are probably enough to consider early palliative cares a novel standard of care in these groups of patients.

Introduction: Febrile Neutropenia (FN) secondary to chemotherapy is the most common and the earliest hematological complication. The aim of this work is to study the predictive factors of FN. Materiel and Methods: This is a retrospective study including 186 episodes of FN induced by chemotherapy treated in the department of oncology at Sfax in southern Tunisia during the period between 1 January 2006 and 31 December 2010. Result: The mean age of patients was 40 years. One hundred and seventeen patients had solid tumors (86.02%), 18 patients (13.23%) had hematological malignancies and one patient was treated for hypo pharyngeal cancer and aplastic Anemia. Chemotherapy was indicated for curative purpose in 94 cases and palliative purpose in 92 cases. One hundred and four patients (76.5%) had a single episode of FN and 32 (23.5%) had at least two episodes. The average time of febrile neutropenia was 11 days. Conclusion: Personal history of FN, poor performance status, chemotherapy regimen and the stage of the disease increased the risk of FN, with a statistically significant difference. Other factors such as hematological malignancies, the age over 65 years and concurrent chemo radiotherapy were not retained in our series.