Pazopanib (Votrient) Approved By The National Institute for Health and Clinical Excellence (NICE) For Treatment Of Advanced Renal Cell Carcinoma

The National Institute for Health and Clinical Excellence (NICE) is recommending Pazopanib (Votrient) as a first-line treatment option for people with advanced renal cell carcinoma (RCC) who have not previously received cytokine therapy and who are of Eastern Cooperative Oncology Group (ECOG) performance status 0-1, on the basis that GSK provided that an agreed patient access scheme agreed. The patient access scheme will offer straight discount of 12.5% (which will bring the price in par with Sunitinib) and makes provision for a possible partial rebate to the NHS in the future. The rebate  is conditional upon the outcome of a head-to-head trial with current standard of care treatment sunitinib (Sutent).
The study, COMPARZ, which started in 2008 will end in May 2011 and the results will be out in Mid 2012.
Usually NICE recommendations are accepted by UK National Health Service and this time NICE has recommended that NHS takes the deal.

Votrient is a type of medicine called a tyrosine kinase inhibitor (TKI) and it has been shown to effectively slow down the progression of advanced RCC whilst maintaining QoL compared with placebo; a significant consideration for patients at an advanced stage of disease.2,3 Votrient has an acceptable and manageable toxicity profile. The most frequent adverse events related to Votrient treatment were diarrhoea, hair colour change, hypertension, nausea, anorexia and increased liver enzymes.

Advanced RCC is an aggressive form of kidney cancer with a poor prognosis, due in part to its resistance to chemotherapy, radiotherapy and hormone therapy. Over 8,000 people in the UK are diagnosed with kidney cancer each year and around one third show signs of advanced RCC at the time of diagnosis.7-9 The introduction of targeted cancer therapies has transformed the management of advanced RCC. However, despite improvements in efficacy, side effects observed with available treatments to date can affect patients’ quality of life and their ability to carry out normal daily activities.12-17 This was acknowledged by the NICE Appraisal Committee in their evaluation of evidence from the patient experts and clinicians. With only one targeted treatment option (sunitinib) recommended by NICE as a first-line treatment until now,18 the NICE recommendation of Votrient will offer patients and clinicians a choice of effective treatment options with different side-effect profiles.

NICE statement

Tumor-Specific Imaging Through Progression Elevated Gene- 3 Promoter, (PEG-Prom) Driven Gene Expression

PEG-Prom mediated reporter expression systems

Researchers may be a step closer to improving the detection of metastatic tumors in an organism — in real time — using a noninvasive approach that pairs an imaging agent with a genetic element that only expresses itself when it is in cancer cells.

The work, a collaborative effort between Virginia Commonwealth University and Johns Hopkins University, could lead to improved and earlier detection of tumors and metastases in patients and allow clinicians to monitor the cancer's response to therapy. The research builds upon a genetic element previously discovered and characterized by a VCU researcher Paul B. Fisher, M.Ph., Ph.D.

In the new study, published online in the December issue of the journal Nature Medicine, VCU researchers, together with researchers from the Johns Hopkins Medical Institutions, have shown how the genetic element, known as progression elevated gene-3 promoter, or PEG-Prom, can be used to image metastases in multiple animal models of human melanoma and human breast metastasis. The system can be used to measure gene expression, protein interaction or track gene-tagged cells in vivo. This approach offers significant advantages in sensitivity and accuracy over currently used imaging strategies.

PEG-Prom, which has been shown to have unique cancer specificity, was originally cloned in Fisher’s laboratory during his time at Columbia University. Fisher is VCU’s principal investigator on the study, and the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research with the VCU Massey Cancer Center.

“The PEG-Prom is the unique aspect of this innovative imaging approach. It is a cancer-specific region of the PEG-3 gene that selectively expresses when in cancer cells. It has minimal expression in normal tissue or animals without cancer,” said Fisher, who also is professor and chair of the Department of Human and Molecular Genetics, and director of the VCU Institute of Molecular Medicine in the VCU School of Medicine.

“This new, non-invasive imaging approach will allow researchers to test chemoprevention strategies and to use repeat applications to follow the course of therapy over time and more accurately define therapeutic outcome and response to therapy than using current methodologies,” he said.

“The potential for this approach to translate into a more effective mode of imaging in humans is extremely high. The benefits to patients would be enormous. One could diagnose tumor formation and cancer that has spread earlier and therefore allow testing of effective therapies. When combined with a therapeutic agent — a radiation emitting compound, a chemotherapeutic agent, or a cytokine such as mda-7/IL-24 — it could in the future permit both imaging and therapy of cancers and metastases (“theranostics”),” Fisher said.

According to Fisher, specific aspects of this technology are patented or in the process of being patented.

This work was supported by grants from the Society of Nuclear Medicine and the Korea Science and Engineering Foundation Fellowship Program, the National Institutes of Health and the National Foundation for Cancer Research.

The senior author was Martin G. Pomper, M.D., Ph.D., professor at Johns Hopkins Medical Institutions. The bulk of the studies described in this paper represent a long-term collaboration between research programs directed by Pomper at Johns Hopkins Medical Institutions and Fisher. The studies were performed by Carrie Bhang, Ph.D., a postdoctoral research scientist in Pomper’s laboratory.

EDITOR’S NOTE: A copy of the study is available for reporters by email request from press@nature.com.
Virginia Commonwealth University
VCU researcher Paul B. Fisher, M.Ph., Ph.D.

Sathya Achia Abraham
VCU Communications and Public Relations
(804) 827-0890
sbachia@vcu.edu

Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo. Tissue-specific promoters can be used to delineate gene expression in certain tissues, particularly when coupled with an appropriate amplification mechanism. Here we show that the progression elevated gene-3 (PEG-3) promoter, derived from a rodent gene mediating tumor progression and metastatic phenotypes, can be used to drive imaging reporters selectively to enable detection of micrometastatic disease in mouse models of human melanoma and breast cancer using bioluminescence and radionuclide-based molecular imaging techniques. Because of its strong promoter activity, tumor specificity and capacity for clinical translation, PEG-3 promoter–driven gene expression may represent a practical, new system for facilitating cancer imaging and therapy. http://www.nature.com/nm/journal/

Aromasin, Arimidex and Femera, Breast Cancer Drugs Increase The Risk Of Heart Diseases.

Breast-cancer drug Aromasin from Pfizer Inc.,  and similar drugs from (Arimidex) AstraZeneca Plc and (Femara) Novartis AG seem to be making women prone to heart diseases. Women taking these drugs are 26 percent more likely to develop heart disease than an older therapy, a study presented today at the San Antonio Breast Cancer Symposium in Texas, found.  All these drugs belong to a family of treatments known as aromatase inhibitors and these halts the production of estrogen, which fuels cancer growth.
Tamoxifen a generic alternative, in use since 1977, proved to be better alternative during the same study.
“It appears that aromatase inhibitors have a significant increase in cardiotoxic side effects, such as heart attack, angina and heart failure, Switching drugs may reduce the side effects.” said Eitan Amir, a senior fellow in oncology and hematology at the Princess Margaret Hospital in Toronto, in a statement. 
via Bloomberg

Scientists Test Histone-modification Antibody Quality.

Scientists all over the world have been busy figuring out how DNA is packaged in cells, because a stretched out DNA strand would be as long as sic feet. But it fits nicely packaged inside a nucleus of one of our cells.   The packaging comprise an amino acid molecule called a histone, mostly and influences the on and off switches of different genes that regulate cellular function and play a role in human diseases ranging from cancer to genetic disorders.

Scientists study histones by using antibodies to specific “flavors” of histones that are only very slightly different from one another. The antibodies help to pinpoint what DNA is being packaged by a certain kind of “flavor” of histone, and how that affects gene regulation. Different flavors affect genes differently.

In a paper published today in the journal Nature Structural and Molecular Biology, Jason Lieb, PhD and his colleagues from across the country describe how they tested more than 200 antibodies against 57 histone  flavors in three different organisms, using three different tests commonly used in this kind of genetic analysis.  They found that about 25 percent of antibodies currently sold have a problem with specificity – targeting the anticipated histone – in a given test.  They believe that this proportion is likely to remain steady over time.

“And this is where it gets complicated, many companies make these antibodies that we scientists use in our labs – but there are so many different kinds of histones and types of tests we do that it’s just not feasible for the companies to anticipate every single way that a given antibody can be used. Histones are essentially the key to the DNA library.  They tell you which ‘shelves’ of that library – or areas of the genome – are open or closed to information moving in and out.  But since the differences between the different ‘flavors’ of histones are often extremely small, and it’s likely that an antibody may react with more than one histone or in different ways depending on the type of test being used in the lab.  It makes scientific precision very difficult. So we thought, OK, we need to help ourselves as scientists.  We set up a web-based searchable database at http://compbio.med.harvard.edu/antibodies.  Our results are there and other scientists can also post their results so that we have a self-sustaining, up-to-date source of information that is really important to scientists working to understand a broad range of genetic phenomena,” says Jason Lieb, PhD, ho is a professor of biology at the University of North Carolina at Chapel Hill and member of UNC Lineberger Comprehensive Cancer Center, and who led the project testing common antibodies.

The research was funded by the National Human Genome Research Institute (part of the United States National Institutes of Health) and included researchers from the Universities of California at Santa Cruz, Berkeley, and San Diego, the Lawrence Berkeley National Laboratory, the Ludwig Institute for Cancer Research, Harvard Medical School, the University of Cambridge (UK), Washington University in St. Louis, Ontario Institute for Cancer Research (Canada) and Rutgers University.
UNC Press Release