Reviews on Recent Clinical Trials

ISSN: 1574-8871

Reviews on Recent Clinical Trials
Volume 4, Number 3, September 2009

Contents


Percutaneous Radiofrequency Ablation for Unresectable Colorectal Liver Metastases: Time for Shadows to Disperse Pp. 140-146
Loukia S. Poulou, Panayiotis D. Ziakas, Vassilia Xila, George Vakrinos, Katerina Malagari, Konstantinos N. Syrigos and Loukas Thanos
[Abstract] [Purchase Article]


Accelerated Hypofractionated Radiotherapy Schedules in Breast Cancer: A Review of the Current Literature Pp. 147-151
Maria Aggeliki Kalogeridi, Nikolaos Kelekis, John Kouvaris, Kalliopi Platoni, George Kyrias, De-mitrios Pectasides and Vassilis Kouloulias
[Abstract] [Purchase Article]


Is there a Benefit from the Concomitant Use of Immunosupression with Anti-TNF in Crohn’s Disease; Heads or Tails? Pp. 152-158
Peter Laszlo Lakatos
[Abstract] [Purchase Article]


Clinical Trials of the Past Decade in the Management of Chronic Kidney Disease Pp. 159-162
Keng -Thye Woo, Kok- Seng and Choong -Meng Chan
[Abstract] [Purchase Article]


The Use of Bevacizumab and Trastuzumab Beyond Tumor Progression: A New Avenue in Cancer Treatment? Pp. 163-167
F. Meriggi, C. Abeni, B. Di Biasi and A. Zaniboni
[Abstract] [Purchase Article]


Chia (Salvia hispanica): A Systematic Review by the Natural Standard Research Collaboration Pp. 168-174
Catherine Ulbricht, Wendy Chao, Katie Nummy, Erica Rusie, Shaina Tanguay-Colucci, Carmen M. Iannuzzi, Jeena B. Plammoottil, Minney Varghese and Wendy Weissner
[Abstract] [Purchase Article]


Rapid Sequence Intubation: A Review of Recent Evidences Pp. 175-178
Alessandro Di Filippo and Chiara Gonnelli
[Abstract] [Purchase Article]


Emerging Antiviral Drugs for Hepatitis C Virus Pp. 179-184
Masaru Enomoto, Akihiro Tamori and Norifumi Kawada
[Abstract] [Purchase Article]


Spectrum of Benign Lesions Mimicking a Malignant Stricture at the Liver Hilum Pp. 185-194
Woubet Tefera Kassahun and Sven Jonas
[Abstract] [Purchase Article]


Parallel Conduction of the Phase I Preventive and Therapeutic Trials Based on the Tat Vaccine Candidate Pp. 195-204
S. Bellino, V. Francavilla, O. Longo, A. Tripiciano, G. Paniccia, A. Arancio, V. Fiorelli, A. Scoglio, B. Collacchi, M. Campagna, A. Lazzarin, G. Tambussi, C. Tassan Din, R. Visintini, P. Narciso, A. Antinori, G. D’Offizi, M. Giulianelli, M. Carta, A. Di Carlo, G. Palamara, M. Giuliani, M.E. Laguar-dia, P. Monini, M. Magnani, F. Ensoli and B. Ensoli
[Abstract] [Purchase Article]


Treatment of Bone Metastases in Lung Cancer: The Actual Role of Zole-dronic Acid Pp. 205-211
Serena Ricciardi and Filippo de Marinis
[Abstract] [Purchase Article]




Abstracts


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Percutaneous Radiofrequency Ablation for Unresectable Colorectal Liver Metastases: Time for Shadows to Disperse
Loukia S. Poulou, Panayiotis D. Ziakas, Vassilia Xila, George Vakrinos, Katerina Malagari, Konstantinos N. Syrigos and Loukas Thanos

Background: Despite the advent of combination chemotherapy regimens achieved within the last decade, long term survival of patients with unresectable metastatic disease from colorectal cancer remains poor.

Thermal ablation procedures, including radiofrequency ablation (RFA), are considered feasible options in treating unresectable hepatic tumors either primary (hepatocellular carcinoma) or metastatic, the latter mainly arising from colorectal cancer. Percutaneous access is the least invasive RFA procedure.

Methods & Results: A MEDLINE review unfolded a significant clinical heterogeneity among published series reporting on percutaneous RFA in hepatic metastatic disease from colorectal cancer, regarding study population, optimal time and treatment schemes pre- and post-RFA intervention. Notwithstanding, percutaneous RFA survival figures were consistently better than front line chemotherapy. Furthermore, a pooled analysis of larger series demonstrated a clear benefit in overall survival (HR 0.51, 95% CI 0.44 to 0.58).

Conclusion: Albeit optimal indications are still pending, percutaneous RFA should nonetheless be considered a viable option in patients with unresectable metastatic disease, as it may prolong survival rates achieved with standard chemotherapy.


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Accelerated Hypofractionated Radiotherapy Schedules in Breast Cancer: A Review of the Current Literature
Maria Aggeliki Kalogeridi, Nikolaos Kelekis, John Kouvaris, Kalliopi Platoni, George Kyrias, De-mitrios Pectasides and Vassilis Kouloulias

Lumpectomy followed by breast irradiation is an alternative to mastectomy for patients with early-stage breast cancer. The purpose of radiation treatment following lumpectomy is to minimize the risk of recurrent cancer in the treated breast with as little toxicity as possible so that good cosmesis and function are maintained.

Conventional fractionation schedules for postlumpectomy radiotherapy give 50 Gy in 2 Gy daily fractions, often with an additional boost to the tumor bed, resulting in treatment being given over 5-7 weeks. Delivering postoperative radiotherapy in a shorter period of time, provided it is as effective as longer treatment regiments, could result in greater convenience for patients. Moreover, given the high incidence of breast cancer, the use of a shorter fractionation schedule would decrease waiting lists in busy radiotherapy departments. We searched the medline (pubmed) and we reviewed all the relevant publications. We concluded that the accelerated hypofractionated schedules are safe in terms of cosmesis and effective in terms of local control.


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Is there a Benefit from the Concomitant Use of Immunosupression with Anti-TNF in Crohn’s Disease; Heads or Tails?
Peter Laszlo Lakatos

Over the last some years the increasing knowledge on the pathogenesis of Crohn’s disease led to the development of a number of biological agents targeting specific molecules involved in gut inflammation, first of all TNF-α and its receptors. Infliximab, adalimumab and certolizumab have been successful in inducing and maintaining remission in Crohn’s disease at both short and long term. This was recently confirmed by a Cochrane meta-analysis and also open label extension follow-up and cohort studies. Emerging new data however indicate that combination therapy with infliximab-azathioprine appears to have added benefit in inducing steroid-free remission and mucosal healing than either infliximab or azathioprine alone in azathioprine-naïve patients with early disease. Similarly the combination of steroids induction and infliximab was efficacious in luminal Crohn’s disease. In contrast, there seems to be no synergism between methotrexate and infliximab. It is also less clear whether it is beneficial to use short or long-term infliximab-azathioprine combination in patients who previously failed therapy with azathioprine. In contrast, combination may potentially be associated with increased risk for infection and cancer. In case control-studies, especially the combination of steroids and anti-TNF and older age increased the risk for infectious complications, while scattered case reports point to the potentially increased risk of a rare form of non-Hodgkin’s lymphoma (Hepatosplenic T cell lymphoma) with the use of azathioprine-anti-TNF combination. The aim of this review is to summarize the benefits and risks for the use combination therapy with TNF-α inhibitors in the treatment of Crohn’s disease.


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Clinical Trials of the Past Decade in the Management of Chronic Kidney Disease
Keng -Thye Woo, Kok- Seng and Choong -Meng Chan

The three main causes of Chronic Kidney Diseases [CKD] are diabetes mellitus, chronic glomerulonephritis and hypertension. CKD is an increasing burden in the community as more patients fall prey to kidney failure. Both dialysis and renal transplantation are expensive modalities of treatment for end stage renal failure [ESRF]. Through the years many clinical trials have been performed to retard the progression of CKD to ESRF. Most of the trials focus on three main strategies which aim at renal retardation, namely, control of hypertension, treatment of proteinuria and control of hyper-cholesterolaemia. More recently, investigators have been exploring the role of high dose ARBs as well as the use of Aliskiren , a renin inhibitor. Early therapeutic intervention is necessary as it will contribute to better chances of minimising glomerular damage and in the case of some, even lead to the improvement of renal function with regression of glomerulosclerosis.


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The Use of Bevacizumab and Trastuzumab Beyond Tumor Progression: A New Avenue in Cancer Treatment?
F. Meriggi, C. Abeni, B. Di Biasi and A. Zaniboni

The use of the Monoclonal Antibodies (MoAbs) Bevacizumab (B) and Trastuzumab (T) beyond clinical progression in colorectal and breast cancer treatment is among the hottest topics in today’s clinical oncology. Both observational and prospective studies, based on a sound preclinical basis, seem to support the notion that, simply replacing the cytotoxic drugs combined with the two MoAbs would provide an additional clinical benefit without stopping the biological agent. The aim of this review is to provide a critical analysis of the available clinical data, while waiting for the confirmatory prospective clinical trials still ongoing.

The strength and the weakness of this innovative strategy, as well as the associated expense and toxicity issues will be discussed.


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Chia (Salvia hispanica): A Systematic Review by the Natural Standard Research Collaboration
Catherine Ulbricht, Wendy Chao, Katie Nummy, Erica Rusie, Shaina Tanguay-Colucci, Carmen M. Iannuzzi, Jeena B. Plammoottil, Minney Varghese and Wendy Weissner

Objective: To evaluate the scientific evidence on chia (Salvia hispanica) including history, folkloric precedent, expert opinion, pharmacology, dosing, interactions, adverse effects, and toxicology. This review serves as a clinical support tool.

Methods: Electronic searches were conducted in ten databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on language or quality of publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion/exclusion criteria are utilized for selection. Grades were assigned using an evidence-based grading rationale.

Results: The available human and non-human studies show possible effectiveness for allergies, angina, athletic performance enhancement, cancer, coronary heart disease (CHD), heart attack, hormonal/endocrine disorders, hyperlipidemia, hypertension, stroke, and vasodilatation. Some evidence also suggests possible anticoagulant, antioxidant, and antiviral effects of Salvia hispanica.

Conclusion: There is limited evidence supporting the efficacy of Salvia hispanica for any indication; thus far, only two clinical studies have examined the effects of Salvia hispanica on cardiovascular disease (CVD) risk factors (including body weight). One study showed some effects on some CVD risk factors, while the other did not. Neither study showed any effects of Salvia hispanica on weight loss. However, the historical use of Salvia hispanica suggests that it is safe for consumption by nonallergic individuals. Further rigorous examination is warranted pertaining to the use of Salvia hispanica as a dietary supplement, as well as in the treatment or prevention of human disease.


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Rapid Sequence Intubation: A Review of Recent Evidences
Alessandro Di Filippo and Chiara Gonnelli

Rapid sequence intubation is an essential bullet in the maintenance of patency of the airway during intubation in emergency. It is a valid method in all those situations where you can not determine whether the patient is fasting or not. But RSI is not applicable in all critically ill patients. The presence of severe acidosis, depletion of intravascular volume, heart failure and severe pulmonary disease may complicate the pre-induction period as the induction, leading to the onset of vasodilatation and hypotension. Another complication is represented by Hypoxemia during the manoeuvre

The algorithm of RSI consists in six steps: pre-oxygenation, premedication, myo-relaxation and induction, intubation, primary and secondary confirmation, post-intubation patient management.

Propofol has replaced Thiopental as the most common intravenous ipnotic. In hypotensive patients Ketamine represents a viable alternative.

Succinylcholine is the most common neuromuscular relaxant used in the RSI.

The not depolarizing NMBAs are an alternative to Succinylcholine. Among these, the most important is the Rocuronium. This drug is characterized by a fairly rapid onset (1-2 min) and an intermediate half-life (45-70 min). The onset depends on the dosage used. The problem that limits the use of Rocuronium is the fact that its duration of action is much longer than that of Succinylcholine, especially when used at higher doses. This problem can be solved through the use of Sugammadex. As a muscle relaxant chelating Sugammadex antagonizes the effects induced by Rocuronium on muscle tissueand quickly resolve the blockade.


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Emerging Antiviral Drugs for Hepatitis C Virus
Masaru Enomoto, Akihiro Tamori and Norifumi Kawada

Infection with hepatitis C virus (HCV) is a global health problem that affects approximately 170 million people worldwide. The current standard therapy with peginterferon alpha plus ribavirin for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1—the most prevalent type of HCV in North America and Europe. Development of new antiviral medicines has been hampered by the lack of an effective cell culture system and small-animal model. Herein we review recent progress in the development of new treatments under investigation in clinical trials, including specifically targeted antiviral therapy for HCV such as NS3/4A protease and NS5B polymerase inhibitors.


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Spectrum of Benign Lesions Mimicking a Malignant Stricture at the Liver Hilum
Woubet Tefera Kassahun and Sven Jonas

There is a broad spectrum of benign disorders of the biliary system that resemble hilar cholangiocarcinoma (HCCA) in terms of clinical, pathologic, and imaging findings. No unifying features were found to characterize patients with benign hilar obstruction and distinguish these patients from those with cholangiocarcinoma. Imaging plays a vital role in aiding the differentiation of benign and malignant disease, defining the location and extent of the process, as well as directing biopsy. However, even when lesions at the liver hilum are detected with the highest sensitivity, none of the imaging modalities can reliably characterize and confirm the underlying type of disease. Excessive reliance on cholangiographic or endoscopic biopsy results is dangerous, because tissue sampling is not always diagnostic and a potentially resectable malignancy can be overlooked. Therefore, the preferred treatment option to patients with suspicious hilar lesions should remain resection for presumed malignancy. Local resection with adequate reconstruction excludes a malignant lesion, and provides means of biliary decompression with low mortality and morbidity rate.


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Parallel Conduction of the Phase I Preventive and Therapeutic Trials Based on the Tat Vaccine Candidate
S. Bellino, V. Francavilla, O. Longo, A. Tripiciano, G. Paniccia, A. Arancio, V. Fiorelli, A. Scoglio, B. Collacchi, M. Campagna, A. Lazzarin, G. Tambussi, C. Tassan Din, R. Visintini, P. Narciso, A. Antinori, G. D’Offizi, M. Giulianelli, M. Carta, A. Di Carlo, G. Palamara, M. Giuliani, M.E. Laguar-dia, P. Monini, M. Magnani, F. Ensoli and B. Ensoli

The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/).

The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adju-vant or intradermic (ID), in the absence of adjuvant, at 7.5 μg, 15 μg or 30 μg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration.

Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers.

Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).


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Treatment of Bone Metastases in Lung Cancer: The Actual Role of Zole-dronic Acid
Serena Ricciardi and Filippo de Marinis

Approximately 30-40% of NSCLC patients develop bone metastases. Bone metastases are associated with a significant increase in skeletal-related events (SREs), including severe bone pain, hypercalcemia, pathological fractures, spinal cord compression. These SREs result in impaired mobility, reduced quality of life, and frequently require therapeutic intervention (radiation therapy, surgery and systemic treatments). The normal balance of formation of new bone by osteoblasts and the resorption of old bone by osteoclasts becomes imbalanced and/or uncoupled, leading to the development of lesions that are osteolytic, osteoblastic, or a combination of both. The current National Comprehensive Cancer Network (NCCN) Clinical Practice Giudelines in Oncology recommend palliative external-beam radiotherapy for the treatment of bone metastases in patients with NSCLC and healthcare professionals treating such patients are urged to consider bisphosphonate therapy. Zoledronic acid is the first and only bisphosphonate that has proven efficacy for the treatment of bone metastases from a broad range of solid tumor types, including lung cancer.