Thyroid Cancer Fight

I was diagnosed with thyroid cancer in Nov., 1999. Surgery and radioactive iodine followed. In Dec., 2006, I found a lump in my neck that turned cancerous. Shortly thereafter, it was found to have metastasized throughout my body and to be untreatable and inoperable. I started a clinical trial with Sutent (sunitinib) since Apr., 2007. In Nov., 2013, the tumors began growing again and I was removed from the Sutent Clinical Trial. I started a clinical trial taking of CEDIRANIB on 04/09/14.

Friday, November 20, 2015

ATA Guidelines Update Thyroid Nodule and Cancer Management

http://www.medscape.com/viewarticle/854765#vp_1

Nancy A Melville

|November 20, 2015 New guidelines from the American Thyroid Association (ATA) offer wide-ranging recommendations on the extensive clinical challenges involved in the management of thyroid nodules and differentiated thyroid cancer (DTC), as rates of nodule detection soar and options for risk assessment for thyroid cancer become at once more advanced yet more complicated. For the first time, a medical oncologist was included among the authors of the guidelines.
"A major goal of these guidelines is to minimize potential harm from overtreatment in a majority of patients at low risk for disease-specific mortality and morbidity, while appropriately treating and monitoring those patients at higher risk," writes the ATA guidelines task force.
In compiling the new "ATA management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer," published online November 18 in Thyroid, the task force of experts conducted an exhaustive review of evidence to update recommendations to reflect the rapid advances in technology and science that have significantly transformed the field since the publication of the previous guidelines in 2009.
"The most notable aspect of the guidelines from my perspective is the extreme depth of coverage and level of detail and nuance included in discussions in support of each recommendation," Keith C Bible, MD, a task-force member and chair of the endocrine malignancies disease–oriented group at the Mayo Clinic Cancer Center, in Rochester, Minnesota, told Medscape Medical News.
"This guideline document is much more detailed and comprehensive than other available guidelines and provides practical clinical guidance for providers so as to encourage thoughtful and individualized patient care," he added.
In total, the guidelines include 101 recommendations, including some important changes from the 2009 guidelines as well as new sections altogether on issues including: the follow-up of patients with thyroid nodules who do not have a biopsy; molecular testing for patients with indeterminate cytology; assessing the risk for recurrence; management of voice and parathyroid issues around surgery; and the definition and management of radioiodine-refractory DTC.
First Time a Medical Oncologist Included in Task Force
The task force for the new guidelines is also the first to include a medical oncologist, helping with guidance on issues such as the use of kinase inhibitors for DTC, Dr Bible noted.
"[A lot of] new data have emerged related to the use of kinase inhibitors as therapeutics in progressive, metastatic, and symptomatic DTC patients," he explained. "The 2015/16 guidelines are considerably expanded and revised in this respect, with two kinase inhibitors, sorafenib [Nexavar, Bayer] and lenvatinib [Lenvima, Eisai], now subject to regulatory approval in the US and the European Union for use in DTC."
The guidelines specifically make a weak recommendation, based on moderate-quality evidence, that kinase-inhibitor therapy be considered in DTC patients who fail to respond to radioactive-iodine therapy or who have metastatic, rapidly progressive, symptomatic, or imminently threatening disease.
Another notable change in the guidelines is a shift in recommendations on the use of radioactive iodine in patients with thyroid cancer, which may spark some debate, Dr Bible said.
"The new guidelines present I think a more nuanced approach to the use of radioactive iodine," he explained.
"[There is a] move further away from recommending uniform use of radioactive iodine in all thyroid-cancer patients, leaving some proponents of radioactive-iodine therapy unhappy with the guidelines."
According to the new recommendations, radioactive-iodine remnant ablation after thyroidectomy is not routinely recommended for low-risk DTC patients or after lobectomy or total thyroidectomy for patients with unifocal or multifocal papillary microcarcinoma in the absence of other adverse features. The recommendation is classified as "weak," based on low-quality evidence.
Radioactive-iodine adjuvant therapy, meanwhile, "should be considered" after total thyroidectomy in DTC patients with intermediate risk and is routinely recommended after total thyroidectomy in patients at high risk, according to the guidelines. The recommendation is also classified as weak, based on low-quality evidence.
Guidance on Surgery for DTC, Management of Thyroid Nodules
Another key change is the recommendation that lobectomy or thyroidectomy are both reasonable surgical approaches for DTC 1 to 4 cm, a shift from 2009 guidelines, which recommended thyroidectomy for all nodules larger than 1 cm, explained Bryan R Haugen, MD, of the University of Colorado, Aurora, who led the task force.
Another recommendation, that thyroid nodules smaller than 1 cm do not need to be biopsied and that not all larger than 1 cm need to be biopsied, is the subject of debate, challenged in a study presented last month at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA).
In that study, which looked at nearly 1000 thyroid nodules, researchers found no significant difference in prognosis and disease recurrence between nodules that were smaller than 1 cm compared with those larger than 1 cm.
Factors that did show statistically significant association with the highest risk included extrathyroid extension, aggressive histology, positive surgical margins, and capsular or lymphovascular invasion.
Senior author Emad Kandil, MD, chief of the endocrine surgery section at Tulane University School of Medicine, in New Orleans, Louisiana, told Medscape Medical News that choosing not to cytologically evaluate smaller nodules, as is the new ATA recommendation, "may not be justified in the light of identical outcomes and disease recurrence risk as for larger nodules."
This is because "larger people will have larger thyroids and smaller people will have smaller thyroids, so we can't just focus on size of nodules," Dr Kandil explained. "The focus should be on molecular markers and not just the size."
Dr Haugen responded that the researchers' conclusion "is a reasonable caution" but noted that ATA advocates only omitting cytological evaluation with fine-needle aspiration"in those patients who have ultrasound features that do not indicate a concern, such as no abnormal lymph nodes and no ultrasound evidence of extrathyroid extension or tumor at the capsule of the thyroid gland." He also noted that Dr Kandil and colleagues "did not analyze for these features preoperatively."
Discovering the presence of a positive BRAF mutation is not turning out to be as predictive of risk as once thought, Dr Haugen said. "We are still cautioning that forgoing fine-needle aspiration in patients with sonographically suspicious nodules smaller than 1 cm should be done only in carefully selected patients."
Epidemic of Thyroid Cancer
Recommendations are likely to continue to evolve as detection rates of thyroid cancers rise, adding to the pressing need for more evidence to help guide clinical decision making, Dr Bible stressed.
"There is an 'epidemic' of papillary thyroid cancer noted worldwide, particularly in developed countries, apparently arising primarily due to increased detection of minute papillary cancers, either from intentional thyroid-cancer screening (for instance, in South Korea) or by incidental detection from the increasing use of medical imaging (for instance, in the United States)," he explained.
"Available data suggest that the vast majority of these micropapillary cancers would not have previously been recognized and furthermore suggest that most appear to be indolent and not requiring of aggressive therapy — but more evidence is required to define how to respond most appropriately."
Dr Haugen has received grant/research support from Veracyte and Genzyme, as well as a one-time speaker honorarium from Genzyme. Dr Bible has no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Dr Kandil has no relevant financial relationships.
Thyroid. Published online November 18, 2015. Article

Cite this article: ATA Guidelines Update Thyroid Nodule and Cancer Management. Medscape. Nov 20, 2015.

Thursday, November 19, 2015

Lab-grown vocal cords may one day treat voice disorders

http://www.cbsnews.com/news/lab-grown-vocal-cords-may-one-day-treat-voice-disorders/

Friday, November 6, 2015

Advanced Thyroid Cancer Responds Well to Targeted Therapies

http://www.targetedonc.com/conference/cfs-2015/advanced-thyroid-cancer-responds-well-to-targeted-therapies

To further build upon these results, the phase II UPCC 19309 trial gave patients with metastatic DTC who were progressing despite prior therapy with sorafenib a combination of sorafenib and everolimus (Afinitor). PFS was the primary endpoint of the study.

The median PFS with the combination was 13.9 months (95% CI, 7.15-24.75). There was 1 partial response among the 33 evaluable patients enrolled in the study (3%). Additionally, 18 patients had stable disease for ≥6 months, for a clinical benefit rate of 58%.

These findings were surprising, since an earlier study exploring the combination had caused toxicity, for a reason that is not yet understood, said Brose. Further analysis of data from this study showed patients with PFS over 40 months, she added. Given the level of efficacy seen, further clinical trials are planned to confirm the results. - See more at: http://www.onclive.com/conference-coverage/CFS-2015/targeted-therapies-improve-outcomes-in-advanced-thyroid-cancer#sthash.TL6KN1bK.dpuf
- See more at: http://www.targetedonc.com/conference/cfs-2015/advanced-thyroid-cancer-responds-well-to-targeted-therapies#sthash.MRSCiHGI.dpuf

The treatment paradigm for advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in all ages has been greatly changed due to kinase inhibitors sorafenib (Nexavar) and lenvatinib (Lenvima), with combination strategies hoping to further build upon this success, Marcia Brose, MD, told physicians at the 33rd Annual Chemotherapy Foundation Symposium.

Over 65,000 new cases of DTC and 2000 deaths are expected this year, said Brose, director of the Thyroid Cancer Therapeutics Program at the University of Pennsylvania. In 5% to 15% of patients, the disease becomes RAI-refractory, with median survival estimated at 2.5 to 3.5 years.

Prior to sorafenib becoming the first kinase inhibitor approved for RAI-refractory DTC in 2013, the ineffecitve chemotherapy doxorubicin was the standard, Brose said, with the pivotal phase III DECISION trial being the first successful analysis of a kinase inhibitor in this setting.

“Here we had patients with definite evidence of progression, as well as evidence of RAI-refractory [DTC] either because the disease did not take up radioactive iodine or because the disease took up radioactive iodine and grew anyway,” Brose said.

In the study, 417 patients were randomized in a 1:1 ratio to sorafenib or placebo, and crossover was allowed at the time of progression, with the primary endpoint of progression-free survival (PFS). The sorafenib cohort had a PFS of 10.8 months; whereas, PFS for the placebo group was 5.8 months (HR, 0.587; 95% CI, 0.454–0.758; P <.0001).

In 2015, the multikinase inhibitor lenvatinib joined sorafenib as an approved therapy for patients with RAI-refractory DTC. This agent demonstrated value for patients with progression on prior sorafenib, Brose said.

In the phase III SELECT study, patients were randomized in a 2:1 ratio to lenvatinib or placebo. A portion of these patients had received prior VEGF/VEGFR-targeted therapy, providing hints at an optimal sequence for these therapies.

In the full population, lenvatinib achieved an 18.3-month PFS versus 3.6 months for placebo. “This is clearly a different population than the DECISION trial, with patients more rapidly progressing,” Brose said.

“In the second-line, we also had a very good PFS, at 15.1 months. Now, it’s been argued by some that because it’s active in the second-line that lenvatinib can be used in the first- or second-line after sorafenib, whereas others argue lenvatinib is suitable for first-line treatment only,” Brose said. “I think both are true, and I think it’s just very good for our patients that we now have two lines of therapy.”

Further data from the SELECT trial indicated that patients over 65 years did well, achieving 16.7-month PFS versus 20.2 months for the younger group. The risk of death in this group was reduced by 47% with lenvatinib (HR, 0.53; CI, 95%, 0.31-0.91), marking this as the first survival benefit for older patients with DTC.

“What really caught our eye is that treatment with lenvatinib improved their overall survival to that actually comparable or at least within range of the patients who are under 65,” Brose said.

To further build upon these results, the phase II UPCC 19309 trial gave patients with metastatic DTC who were progressing despite prior therapy with sorafenib a combination of sorafenib and everolimus (Afinitor). PFS was the primary endpoint of the study.

The median PFS with the combination was 13.9 months (95% CI, 7.15-24.75). There was 1 partial response among the 33 evaluable patients enrolled in the study (3%). Additionally, 18 patients had stable disease for ≥6 months, for a clinical benefit rate of 58%.

These findings were surprising, since an earlier study exploring the combination had caused toxicity, for a reason that is not yet understood, said Brose. Further analysis of data from this study showed patients with PFS over 40 months, she added. Given the level of efficacy seen, further clinical trials are planned to confirm the results. - See more at: http://www.onclive.com/conference-coverage/CFS-2015/targeted-therapies-improve-outcomes-in-advanced-thyroid-cancer#sthash.TL6KN1bK.dpuf
- See more at: http://www.targetedonc.com/conference/cfs-2015/advanced-thyroid-cancer-responds-well-to-targeted-therapies#sthash.MRSCiHGI.dpuf

Wednesday, November 4, 2015

New Thyroid Cancer Guidelines Reflect Altered Treatment Landscape

https://www.mskcc.org/blog/new-thyroid-guidelines-reflect-altered-treatment-landscape

By Miriam Falco

on Monday, November 2, 2015

Newly released thyroid cancer treatment recommendations from the American Thyroid Association (ATA) suggest that monitoring an early-stage papillary thyroid tumor — instead of removing it — can be a very reasonable option.

For nodules or tumors smaller than one centimeter that appear to be confined to the thyroid gland, the new guidelines say, patients may be able to avoid immediate surgery and instead have the tumor observed to see if it grows.

This suggestion is one notable aspect of the ATA guidelines, published in October, which consist of treatment recommendations that address screening, staging, risk assessment, and surgical approaches for thyroid cancer.

“The new guidelines are all about risk stratification and are completely removing one-size-fits-all treatment recommendations,” says Memorial Sloan Kettering endocrinologist Michael Tuttle, who has been actively involved in shaping these guidelines. “Now treatment will be individualized for high- and low-risk patients.”

In many cases, the new recommendations reflect a prevailing sentiment among thyroid cancer experts that less extensive treatment often produces the best outcomes for patients because most very small thyroid cancers grow quite slowly and never pose a threat.

In fact, the ATA guidelines advise that growths smaller than one centimeter that do not need treatment should not even be biopsied. And in cases in which surgery is required, the guidelines say that partial removal of the thyroid (lobectomy) should be considered instead of always performing a total thyroidectomy.

Richard Wong, Chief of MSK’s Head and Neck Service, says the guidelines will help prevent unnecessary ultrasounds and needle biopsies and will help reduce the “overdiagnosis of a condition in which the treatment could be more problematic than the underlying disease.”

Overdiagnosis and Overtreatment

Thyroid cancer has been on the rise in the United States over the last several decades, more than doubling between 1973 and 2002. The detection of small thyroid cancers especially increased with the introduction of ultrasounds into routine practice in the 1990’s. Since that time, it has become clear that most of these very small thyroid cancers grow slowly and never pose a threat.

As a result, physicians at MSK and elsewhere have come to recognize that a large number of patients were being biopsied or treated unnecessarily. The new ATA guidelines will help patients and physicians figure out when to intervene and when to take a more conservative approach.

The guidelines recommend practices that in most cases are already followed at MSK. For example, the watchful waiting technique — also known as “active surveillance”— used with early-stage papillary thyroid tumors is already part of MSK’s approach. The new ATA guidelines are significant because they “formally endorse observation” as a possible treatment option, Dr. Tuttle says.
“If at some point we decide that a tumor we have been watching should be removed, the surgical treatment will almost certainly be just as effective in the future as it would have been if we took it out when it was diagnosed,” he says “While some small tumors are not appropriate for this method — depending on location and other factors — these make up a tiny group.”

Dr. Wong points out that most physicians and hospitals do not currently have an active-surveillance program. He adds that the new ATA guidelines will make practitioners more comfortable with the concept of observing a tiny cancer that is statistically highly unlikely to ever cause harm.
MSK has also been on the forefront with the approach of selecting the more conservative surgery, lobectomy, for low-risk thyroid cancers, Dr. Wong explains. The ATA guidelines are now more supportive of this concept for selected cancers. Research published more than two decades ago by former MSK Head and Neck Service Chief Jatin Shah and surgical oncologist Ashok Shaha supported such an approach, which was somewhat controversial at the time. “It is gratifying to see how the academic thyroid community has finally followed their lead,” Dr. Wong says.

Thursday, October 29, 2015

Genetically Modified Super Tomato May Help Fight Cancer, Diabetes And Alzheimer’s Disease

http://www.techtimes.com/articles/100488/20151028/genetically-modified-super-tomato-may-help-fight-cancer-diabetes-and-alzheimer-s-disease.htm

By Katherine Derla, Tech Times | October 28, 3:29 AM

A study led by John Innes Centre researchers in the United Kingdom (UK) resulted in the mass production of natural compounds in a single, genetically modified fruit - a tomato. These compounds include life-extending Resveratrol found in wine and Genistein found in tofu which has cancer-preventing benefits.

By introducing a protein called AtMYB12, which is normally found in a garden weed called thale cress (Arabidopsis thaliana), scientists found that the protein activates a wide set of genes responsible for natural compound production in the tomato plant. The AtMYB12 acts like a plug or tap that scientists can control to reduce or increase the amount of natural compounds that can benefit the plant and in turn, humans.
The researchers noted that the introduction of the AtMYB12 protein did not only increase the plant's ability to create the Resveratrol and Genistein, it also influenced the plant's ability to devote more carbon and energy in the compound creation.

"Medicinal plants with high value are often difficult to grow and manage, and need very long cultivation times to produce the desired compounds. Our research provides a fantastic platform to quickly produce these valuable medicinal compounds in tomatoes. Target compounds could be purified directly from tomato juice," said co-author Dr. Yang Zhang
The research team is optimistic that the same genetic switching technique can be used to mass manufacture other natural compounds involved in the production of several medicines. Tomatoes are relatively cheap to produce and can be turned into juice form where the compounds can be extracted. Eventually, the fruit itself could soon become a medicinal plant with increased levels of illness-fighting compounds.

The study provides a basis for a more cost-efficient industrial production of valuable natural compounds from plants compared to extracting small amounts from tons of soybeans and grapes. The researchers believe their design can be applied to other compounds such as alkaloids and terpenoids.

Co-author Cathie Martin stressed that their study delivers a design to mass produce not just phenylpropanoid compounds but potentially more natural compounds that can extracted from aromatic amino acids.

The researchers published their study in the Nature Communications journal on Oct. 26.

Camomile tea could improve blood glucose control in type 2 diabetes

http://www.diabetes.co.uk/news/2015/oct/camomile-tea-could-improve-blood-glucose-control-in-type-2-diabetes-91406398.html

Jack Woodfield
Tue, 27 Oct 2015

An Iranian study finds that drinking three cups of camomile tea a day could improve control of blood glucose levels in people with type 2 diabetes.

Researchers from Tabriz University of Medical Sciences aimed to investigate how the effects of camomile tea would affect glycemic control and antioxidant levels in type 2 subjects. Antioxidants are chemicals that protect or delay against cell damage.

64 participants with type 2 diabetes were recruited, all of whom were aged between 30 and 60. They consumed camomile tea three times per day immediately after meals for eight weeks. A control group also followed this routine, but they drank water instead.

The camomile tea group had significantly reduced HbA1c and serum insulin levels, as well as significantly increased total antioxidant capacity compared to those in the control group.

The researchers concluded that camomile tea could be useful in reducing diabetes risk factors. They added: "Short-term intake of chamomile tea has beneficial effects on glycemic control and antioxidant status in patients with type 2 diabetes."

However, the researchers noted that a larger sample population and a longer intervention period would be necessary in order to demonstrate significant clinical improvements.

This study was published in the journal Nutrition.

Wednesday, October 28, 2015

Vemurafenib/Sorafenib Combo Shows Promise in Papillary Thyroid Carcinoma

http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma

W. Todd Penberthy, PhD

Published Online: Thursday, October 22, 2015

- See more at: http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma#sthash.JZnsUABZ.dpuf

W. Todd Penberthy, PhD

Published Online: Thursday, October 22, 2015

Published Online: Thursday, October 22, 2015

Interesting article but for some reason it won't let me copy and paste. Check it out at the website above.

Dual targeting of BRAF V600E–positive papillary thyroid carcinoma (PTC) with the anti-BRAF V600E agent vemurafenib (Zelboraf) and the angiogenesis inhibitor sorafenib (Nexavar) showed promising clinical activity, according to research presented at the 2015 International Thyroid Congress.

Sorafenib was approved in 2013 for the treatment of locally recurrent or metastatic, progressive differentiated thyroid carcinoma refractory to radioactive iodine treatment. Antitumor activity with vemurafenib in BRAF V600E–positive PTC was previously demonstrated in a phase II study presented at the 2013 European Cancer Congress. In the study, the median progression-free survival in treatment-naïve patients who received vemurafenib was 15.6 months.

Carmelo Nucera, MD, PhD, assistant professor at Harvard Medical School, and colleagues used cell cultures of human metastatic/recurrent BRAF V600E -PTCs and tested the effects of vemurafenib versus sorafenib used as single agents or in combination. To date, they have used predominately three types of assays. These include biochemical assays of enzyme activity along with two dynamic cellular assays—measures of cell-cycle proliferation and in vitro microenvironmental analysis: migration and motility.

Nucera pointed out that BRAF V600E PTCs responded to vemurafenib than sorafenib. In contrast, with wild-type BRAF cells, the BRAF inhibitor does not work and sorafenib works very well. Ultimately the combination overlaps in activity, Nucera said.

The key, according to Nucera, is tumor heterogeneity, and therefore, the tumor microenvironment needs to be considered. Macrophages, for example, are an important component in the anaplastic pericyte microenvironment. Macrophages and endothelial cells exist in this microenvironment.

Nucera’s group observed that the pericytes act like stem cells, interacting with endothelial cells to regulate angiogenesis. Pericytes spread after exposure to various signaling molecules like PDGFR-β, according to Nucera. Pericytes have a strong capability to produce an extracellular matrix, which may ultimately confer advantage to PTC cells to promote their migration and invasion.

Higher PDGFR-β was observed by Nucera et al in BRAF V600E cells than in the wild-type equivalent, but addition of a BRAF inhibitor caused down-regulation of PDGFR-β activation. No response was seen after sorafenib treatment, while the combination belies the treatment of the single sorafenib agent.

Nucera’s study preliminarily suggests that the combination of an antiangiogenic compound and a BRAF inhibitor may be more effective than either agent alone, not only in blocking the proliferation of PTC cells, but also in preventing cell types like pericytes in the microenvironment from promoting otherwise reproductive advantages to PTC cells.

Nucera highlighted that these results indicate for the first time that PTC cells express VEGFR2, and this dual combination treatment with anti–BRAF V600E and antiangiogenesis therapy is likely to improve therapeutic response in metastatic BRAF V600E–positive PTC cells by directly reducing cell survival and migratory capacities via pERK1/2 and pPDGFR-β down-regulation.

Richard Kloos, MD, cochair for the session and professor of Medicine at Ohio State University, stated that the value of adding sorafenib must be that the BRAF activity is not strong enough. Kloos then asked whether or not the sorafenib effect is really a dose effect working through BRAF.

Nucera elaborated that the BRAF inhibitor is working on the BRAF system. Therefore, if you use a pan¬–tyrosine kinase inhibitor (TKI) like sorafenib, you can improve the activity to kill any tumor cell, said Nucera. The rationale for using an antiangiogenic agent is that you have a human system with many different cells with many different TK targets. In Nucera’s observations, combining the BRAF inhibition with a pan-TKI will fundamentally work on any tumor cell.

Sisms J, Antonello Z, Nucera C, et al. Combinatorial targeting with anti-BRAFV600E and anti-angiogenesis therapy enhances cell death and suppresses cell migration in metastatic papillary thyroid carcinoma. Presented at: 2015 International Thyroid Congress; October 18-23, 2015; Orlando, FL. Abstract 106.

- See more at: http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma#sthash.JZnsUABZ.dpuf

Published Online: Thursday, October 22, 2015

W. Todd Penberthy, PhD

Dual targeting of BRAF V600E–positive papillary thyroid carcinoma (PTC) with the anti-BRAF V600E agent vemurafenib (Zelboraf) and the angiogenesis inhibitor sorafenib (Nexavar) showed promising clinical activity, according to research presented at the 2015 International Thyroid Congress. - See more at: http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma#sthash.JZnsUABZ.dpuf

- See more at: http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma#sthash.JZnsUABZ.dpuf

W. Todd Penberthy, PhD

Published Online: Thursday, October 22, 2015

- See more at: http://www.onclive.com/conference-coverage/thyroid-2015/vemurafenib-sorafenib-combo-shows-promise-in-papillary-thyroid-carcinoma#sthash.JZnsUABZ.dpuf

Massive screen of drug combinations may find treatment for resistant, BRAF-mutant melanoma

http://medicalxpress.com/news/2015-10-massive-screen-drug-combinations-treatment.html

October 26, 2015

A team of Massachusetts General Hospital (MGH) investigators has discovered a new combination of drugs that may be effective against one of the deadliest cancers, malignant melanoma. The combination - pairing a drug targeted against mutations in the BRAF gene with a second drug that targets another important signaling pathway - was discovered through one of the largest screens of cancer drug combinations conducted to date. Findings from the study conducted at the MGH Cutaneous Biology Research Center and Center for Molecular Therapeutics have published in the open-access journal PLOS ONE.

"We wanted to see whether very-large-scale screening across a diverse collection of cancer cell lines and a large number of drugs could yield new combinations for patients with cancer," says Adam Friedman, MD, PhD, of the CBRC and the MGH Cancer Center, who led the study. "By conducting such a screen, we found one specific combination of agents that are already being used clinically that potentially could be used for a specific group of patients - those with BRAF-mutant cancers."

Friedman notes that, even with the increasing number of drugs targeting specific molecular abnormalities that drive tumor growth, most patients are only treated with one such drug at a time. Most of those treated with targeted-therapy drugs will relapse within a year, often because their tumors have become resistant, and some tumors never respond to the targeted drugs. While combining anti-cancer drugs appears a promising strategy, the sheer volume of drugs currently in use or in development - more than 500, which could make up more than 100,000 two-drug combinations - makes testing each potential combination in clinical trials challenging.

Previous efforts to screen potential drug combinations only analyzed use of a few drugs against a limited number of cell lines or lines in which genomic variations were poorly understood. This study utilized 36 well-characterized melanoma cell lines assembled by the MGH Center for Molecular Therapeutics to test all possible combinations of more than 100 oncology drugs, two-thirds of which are currently in clinical use. More than 5,775 potential drug combinations, as well as each single drug, were screened against each cell line, looking for effects on the number and viability of tumor cells. While several combinations showed synergistic effects - with some drugs sensitizing the cells against several other drugs - most combinations increased the response of only one or two cell lines, implying that the vulnerability of an individual patient's tumor to these combinations depends on its unique genetic signature.

Since around half the cases of malignant melanoma are driven by mutation in the BRAF gene, the team focused on combinations that might address intrinsic resistance to the BRAF inhibitor vemurafenib. They found that combining that drug with the cediranib, an investigational drug that targets a group of proteins known to be involved in blood vessel formation, had synergistic effects against cell lines that were resistant to treatment with vemurafenib alone but not those sensitive to single-agent therapy. They also tested this combination in animal models into which two resistant cell lines had been grafted, and found significant synergistic effects against both tumor models.
"We need to confirm this synergistic activity of vemurafenib and cediranib across a broader range of melanoma models, investigate why the particular combination is effective, and find biomarkers that predict which patients with BRAF-mutant melanoma should receive this combination," says Friedman, who is a research fellow in Dermatology at Harvard Medical School. "What is really exciting is that these drugs are already in the clinic; in fact a clinical trial for a similar combination is already underway at another research center. We may be able to quickly improve on the selection criteria for this trial and identify patients whose tumors might respond."

He adds, "This study was actually a pilot project for a much larger effort within the Center for Molecular Therapeutics to map responses against drug combinations across hundreds of cancer cell lines, not just melanoma, and look for novel combinations that will benefit subsets of patients regardless of the particular type of tumor they have. Since our collection of cell lines is completely genetically annotated - which means that mutations and expression changes in each line's genes have been documented - we should be able to identify in advance patients who will benefit from specific combinations. Beyond the specific combination we focused on, this study should help others understand the technical challenges of analyzing such a large combination dataset."

VB-111 May Be Effective in Radioactive Iodine-Refractory Differentiated Thyroid Cancer

http://www.endocrinologyadvisor.com/itc-2015/itc-ata-vb-111-differentiated-thyroid-cancer/article/449338/

Jeff Craven

October 26, 2015

Use of anti-angiogenic VB-111 was associated with improved survival in patients with advanced radioactive iodine-refractory differentiated thyroid cancer, according to new data.
Sina A. Jasim, MD, from the Mayo Clinic in Rochester, Minnesota, said in an email interview with Endocrinology Advisor that most patients respond well to surgery and radioactive iodine therapy (RAI), but other patients with differentiated thyroid cancer develop resistant disease, “which is progressive, symptomatic, and fatal.”

“VB-111 is a non-replicating, engineered AD-5 adenovirus that is selectively targeting tumor vasculature,” Dr Jasim said. “It utilizes a tissue- and condition-specific semi-artificial pre-pro-endothelin promoter to express a pro-apoptotic FAS-chimera transgene that is triggering apoptosis of angiogenic tumor vasculature in response to tumor necrosis factor stimulation.”

Dr Jasim, who presented the data at the 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association, and colleagues explained that VB-111 is a novel approach that could potentially address the need for additional effective therapies.

Their open-label, industry-sponsored, dose-escalating phase 2 study analyzed the safety and efficacy of patients with advanced RAI-refractory differentiated thyroid cancer, where the end point was progression-free survival at 6 months for 25% of patients.

The researchers divided 29 patients into 2 groups that received a single VB-111 infusion at a low dose (3 x 10¹² viral particles) or a high dose (1 x 10¹³ viral particles) every 2 months until disease progression.

Regarding adverse effects, patients reported flu-like symptoms after VB-111 administration, which commonly resolved within less than 2 days.

Results revealed that 35% of patients in the high-dose group and 25% of patients in the low-dose group achieved progression-free survival at 6 months.
At 12 months, progression-free survival was 25% in the high-dose group vs 0% in the low-dose group, which may suggest dose-dependent disease stabilization. However, this finding did not reach statistical significance.

Current results indicate that median survival is 18 months in the low-dose group and 22 months in the high-dose group, although the data are not yet mature, according to Dr Jasim.
Dr Jasim and colleagues reported that 9 patients survived until final follow-up, with 8 patients (47%) in the high-dose group.

The research group is continuing to follow the surviving patients, who have all progressed past 18 months post-treatment.

This study is supported by VBL Therapeutics.

Reference
Jasim S. Poster 638: A Multi-cohort Phase II Trial Of VB-111 In
Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer. Presented at: 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association (ITC/ATA); Oct 18-23, 2015; Lake Buena Vista, Florida.

Tuesday, October 27, 2015

Month off drinking slashes risk of disease: Abstaining found to heal the liver and lower blood pressure and cholesterol levels

http://www.dailymail.co.uk/news/article-3289187/Month-drinking-slashes-risk-disease-Abstaining-heal-liver-lower-blood-pressure-cholesterol-levels.html

Doctors have warned drinkers should abstain for a month to prevent illness
Research has shown it can heal the liver and lower blood pressure levels
Those who gave up for a month also at lower risk of cancer and type 2 diabetes
Researchers claim 'staggering' results can influence drinking guidelines

By Sophie Borland for the Daily Mail

‘The results were staggering,’ said Professor Kevin Moore, who was involved in both experiments. ‘If you had a drug that did this it would be a multi-billion pound market.

‘There was a 40 per cent reduction in liver fat, they lost about three kilograms in weight and their cholesterol levels improved.’

In the second, larger study the London researchers looked at 102 relatively healthy men and women in their forties taking part in a ‘dry January’ campaign.

The women had been drinking an average of 29 units of alcohol a week, almost double the Government guidelines. The men were typically on 31 units, ten too many.

All had blood tests and liver scans and answered detailed questionnaires. Four weeks later the damage caused to their livers by years of heavy drinking had started to repair itself.

Their ‘liver stiffness’ - an indication of disease - had been reduced by 12.5 per cent. Their insulin resistance - a measurement of diabetes risk - had come down by 28 per cent.

Current recommendations state men should not drink more than four units of alcohol a day or 21 a week

They had also lost weight, their blood pressure had dropped, and many said their concentration and sleeping levels had improved. The researchers are due to publish further details, which are expected to show their risk of developing certain cancers was also reduced.

Gautam Mehta, a liver specialist who oversaw the study, said: ‘I am excited. There are some findings that will be pretty novel. It’s an important study which shows the benefit from a month’s abstinence. What we can’t say is how long those benefits are, how durable those benefits are.’

The initial results are already being examined by Department of Health officials, who are preparing new guidelines on safe drinking.

Current recommendations state women should have no more than three units a day or 14 units over a week while men should not exceed four units a day or 21 a week.

One unit is equivalent to less than half a glass of wine or half a pint of beer depending on their strength and size.

But health professionals say these limits should be reduced. They also want adults to be told to have at least two or three days off a week to allow their bodies to recover.

The Royal Free’s first experiment was on ten men and women undertaking a dry January last year.

Tom Smith of Alcohol Concern said: ‘This evidence confirms what a growing number of other studies have shown, that having even just one month off from alcohol has incredible health benefits.’

Andrew Langford of the British Liver Trust said: ‘It provides good evidence that simple behavioural change can make a real difference to the health of your liver.’

Massive screen of drug combinations may find treatment for resistant, BRAF-mutant melanoma

This is interesting because it involved a mutation I have (BRAF, common in Thyroid Cancer as well as Melanoma) and is using the drug I am on in combination with another.

http://medicalxpress.com/news/2015-10-massive-screen-drug-combinations-treatment.html

October 26, 2015

A team of Massachusetts General Hospital (MGH) investigators has discovered a new combination of drugs that may be effective against one of the deadliest cancers, malignant melanoma. The combination - pairing a drug targeted against mutations in the BRAF gene with a second drug that targets another important signaling pathway - was discovered through one of the largest screens of cancer drug combinations conducted to date. Findings from the study conducted at the MGH Cutaneous Biology Research Center and Center for Molecular Therapeutics have been published in the open-access journal PLOS ONE.

We wanted to see whether very-large-scale screening across a diverse collection of cancer cell lines and a large number of drugs could yield new combinations for patients with cancer," says Adam Friedman, MD, PhD, of the CBRC and the MGH Cancer Center, who led the study. "By conducting such a screen, we found one specific combination of agents that are already being used clinically that potentially could be used for a specific group of patients - those with BRAF-mutant cancers."

Friedman notes that, even with the increasing number of drugs targeting specific molecular abnormalities that drive tumor growth, most patients are only treated with one such drug at a time. Most of those treated with targeted-therapy drugs will relapse within a year, often because their tumors have become resistant, and some tumors never respond to the targeted drugs. While combining anti-cancer drugs appears a promising strategy, the sheer volume of drugs currently in use or in development - more than 500, which could make up more than 100,000 two-drug combinations - makes testing each potential combination in clinical trials challenging.

Previous efforts to screen potential drug combinations only analyzed use of a few drugs against a limited number of cell lines or lines in which genomic variations were poorly understood. This study utilized 36 well-characterized melanoma cell lines assembled by the MGH Center for Molecular Therapeutics to test all possible combinations of more than 100 oncology drugs, two-thirds of which are currently in clinical use. More than 5,775 potential drug combinations, as well as each single drug, were screened against each cell line, looking for effects on the number and viability of tumor cells. While several combinations showed synergistic effects - with some drugs sensitizing the cells against several other drugs - most combinations increased the response of only one or two cell lines, implying that the vulnerability of an individual patient's tumor to these combinations depends on its unique genetic signature.

Since around half the cases of malignant melanoma are driven by mutation in the BRAF gene, the team focused on combinations that might address intrinsic resistance to the BRAF inhibitor vemurafenib. They found that combining that drug with the cediranib, an investigational drug that targets a group of proteins known to be involved in blood vessel formation, had synergistic effects against cell lines that were resistant to treatment with vemurafenib alone but not those sensitive to single-agent therapy. They also tested this combination in animal models into which two resistant cell lines had been grafted, and found significant synergistic effects against both tumor models.
"We need to confirm this synergistic activity of vemurafenib and cediranib across a broader range of melanoma models, investigate why the particular combination is effective, and find biomarkers that predict which patients with BRAF-mutant melanoma should receive this combination," says Friedman, who is a research fellow in Dermatology at Harvard Medical School. "What is really exciting is that these drugs are already in the clinic; in fact a clinical trial for a similar combination is already underway at another research center. We may be able to quickly improve on the selection criteria for this trial and identify patients whose tumors might respond."

He adds, "This study was actually a pilot project for a much larger effort within the Center for Molecular Therapeutics to map responses against drug combinations across hundreds of cancer cell lines, not just melanoma, and look for novel combinations that will benefit subsets of patients regardless of the particular type of tumor they have. Since our collection of cell lines is completely genetically annotated - which means that mutations and expression changes in each line's genes have been documented - we should be able to identify in advance patients who will benefit from specific combinations. Beyond the specific combination we focused on, this study should help others understand the technical challenges of analyzing such a large combination dataset."

Explore further: New screening approach identified potential drug combos for difficult-to-treat melanomas
More information: PLOS ONE, journals.plos.org/plosone/article?id=10.1371/journal.pone.0140310

Journal reference: PLoS ONE

Monday, October 26, 2015

The latest study about antioxidants is terrifying. Scientists think they may boost cancer cells to spread faster.

Good Grief, is anything safe?!?

https://www.washingtonpost.com/news/to-your-health/wp/2015/10/14/antioxidants-may-give-a-boost-to-cancer-cells-making-them-spread-faster-study-suggests/

By Ariana Eunjung Cha October 16

Since the term "antioxidants" made the leap from the realm of biochemistry labs and into the public consciousness in the 1990s, Americans have come to believe that more is better when it comes to consuming the substance that comes in things like acai berries, green tea and leafy veggies.
A provocative new study published Wednesday in the journal Nature raises important questions about that assumption.
Antioxidants — which include vitamins C and E and beta-carotene, and are contained in thousands of foods — are thought to protect cells from damage by acting as defenders against something called "free radicals" which the body produces as a part of metabolism or that can enter through the environment.
That's all great for normal cells. But what researchers at the University of Texas Southwestern Medical Center found is that antioxidants can work their magic on cancerous cells, too — turbo-charging the process by which they grow and spread.
Researcher Sean Morrison and his colleagues conducted experiments on mice that had been transplanted with skin cancer cells (melanoma) from human patients. They gave nothing to one group. To the other they gave doses of N-acetylcysteine (NAC) which is a common antioxidant that's used in nutritional and bodybuilding supplements and has been used as a treatment for patients with HIV/AIDS and in some children with certain genetic disorders.
The results were alarming: Those in the second group had markedly higher levels of cancer cells in their blood, grew more tumors and the tumors were larger and more widespread than in the first.
"What we're starting to learn is that there can be bad cells from cancer that appear to benefit more from antioxidants than normal cells," he said in an interview.

Morrison, director of the Children’s Medical Center Research Institute at UT Southwestern, explained that it has to do with something called oxidative stress.
Scientists have known for a while now that cancer metastasis — especially when it involves spreading a great distance to another part of the body — is a very inefficient process and that many cells die along the way. This is likely due to oxidative stress, which is an inability by the body to counteract the harmful effect of free radicals. When antioxidants supplements are given, the paper hypothesizes, they may give new life to those cancerous cells that are on the edge of dying.

Morrison said that previous studies have shown that the progression of metastasis of human melanoma cells in mice is predictive of their metastasis in humans, which raises concerns about the use of dietary antioxidants by patients with cancer.
Moreover, melanoma may not be the only type of cancer to be affected this way.
A similar study conducted at Vanderbilt University and published in PLoS One in 2012 involving mice with prostate cancer also showed that antioxidants appeared to increase the proliferation of cells in the pre-cancerous lesions. And another one in rodents with lung cancer published in Science Translational Medicine in 2014 found that normal doses of vitamin E and smaller doses of acetylcysteine, an antioxidant supplement, appeared to lead to a three-fold increase in the number of tumors and caused them to be more aggressive. As a result, the mice given antioxidants died twice as fast the ones in the control group. The reaction appeared be dose dependent with larger doses leading to a more severe reaction.
Morrison said that further study needs to be done to confirm the findings and that cancer patients should still consume antioxidants as part of a healthy diet.
But, he added, "personally, from the results we've seen, I would avoid supplementing my diet with large amounts of antioxidants if I had cancer."
Over the past 20 years, numerous studies were launched to ascertain the effect of antioxidants on other conditions ranging from heart disease to memory loss. Early results have mostly been mixed, but that hasn't stopped food companies from hyping their disease-fighting abilities.

PD-L1 Strongly Correlates with Papillary Thyroid Cancer Aggressiveness

http://www.targetedonc.com/conference/ata-2015/pd-l1-strongly-correlates-with-papillary-thyroid-cancer-aggressiveness

W. Todd Penberthy, PhD

Published Online: 2:05 PM, Fri October 23, 2015

- See more at: http://www.targetedonc.com/conference/ata-2015/pd-l1-strongly-correlates-with-papillary-thyroid-cancer-aggressiveness#sthash.G9T2k0uM.dpuf

Investigators at the Mount Sinai School of Medicine, Toronto, Canada, have been working on determining whether or not PD-L1 expression levels and tissue (sub)locali - See more at: http://www.targetedonc.com/conference/ata-2015/pd-l1-strongly-correlates-with-papillary-thyroid-cancer-aggressiveness#sthash.G9T2k0uM.dpuf

TERT/BRAF Mutations a Deadly Combo for Thyroid Cancer Patients

http://www.cancernetwork.com/ata-2015-thyroid-cancer/tert-braf-mutations-deadly-combo-thyroid-cancer-patients

The coexistence of mutations in telomerase reverse transcriptase (TERT) and BRAF genes dramatically increases the risk of thyroid cancer aggressiveness, tumor recurrence and thyroid cancer-specific deaths, confirmed research teams from the United States and Korea at the 15th International Thyroid Congress (ITC) and 85th Annual Meeting of the American Thyroid Association (ATA) in Lake Buena Vista, Florida.
“BRAF V600E and TERT promoter mutations each alone have a modest effect, but the two coexisting, had a robustly synergistic effect on PTC [papillary thyroid cancer]-specific patient mortality,” reported Mingzhao Xing, MD, PhD, of the division of endocrinology and metabolism at Johns Hopkins University School of Medicine in Baltimore, Maryland.
Dr. Xing, the lead author of the US study, presented preliminary data on the TERT/BRAF mutations’ deadly synergy at last year’s ITC/ATA meeting, and this year presented data with a larger cohort of patients and longer follow-up time.
“The two mutations together are associated with much worse outcomes,” Dr. Xing said. “Coexisting BRAF V600E and TERT promoter mutations define a unique genetic background that robustly underpins the worst PTC-specific mortality.”
The coexistence of TERT mutation and BRAF—or RAS—mutations increases tumor recurrence, mortality, and “several aggressive clinicopathologic features” among patients, agreed the lead author of the Korean study, Young Shin Song, MD, of the Seoul National University College of Medicine in South Korea. Dr. Song reported his team’s study of TERT promoter mutations in patients with differentiated thyroid cancer in Korea.
BRAF is a well-recognized proto-oncogene and TERT mutations are suspected to lengthen chromosomal telomeres to immortalize cell lines, in part by evading apoptosis. However, it is not yet clear exactly how these particular mutations interact so powerfully in thyroid cancer.
Of the TERT mutations, C228T is the most common in thyroid cancers, Dr. Xing reported. The US team therefore focused on C228T mutation’s associations with the natural history and outcomes of PTCs. They followed 1,059 patients (764 of whom were female) who were diagnosed with PTC between 1990 and 2015. Using Sanger sequencing of primary PTC tumor genomes, they identified BRAF V600E and TERT C228T mutation status for each patient’s tumors, and analyzed associations between mutation status and patient outcomes.
The US researchers reported that during their study period, only four patients whose PTC harbored neither mutation, died of their disease—a PTC-specific mortality of less than 1 death per 1,000 person-years. “Almost no patients died—very few,” remarked Dr. Xing. Among patients with TERT or BRAF mutations alone, there were four and seven deaths, respectively, yielding PTC-specific mortality rates of 6.6 and 3 deaths per 1,000 person-years. But for patients whose PTC tumors harbored both TERT and BRAF mutations, the US team identified 15 deaths, representing a PTC-specific mortality rate of 29.86 deaths per 1,000 person-years. The associated unadjusted hazard ratio (HR) was 37.77 (95% confidence interval [CI], 12.50–114.09), Dr. Xing reported. That HR dropped to a still-dramatic 9.34 after statistically adjusting the analysis for patient age, sex, tumor size, tumor multifocality, extrathyroidal extension, vascular invasion, and cervical lymph node metastasis, he noted.
The Korean researchers studied 551 patients with DTC (432 of whom had PTC), who underwent thyroidectomy between 1993 and 2012, among whom the overall prevalence of TERT C228T and C250T mutations was 4.5%. “This mutation was found more frequently in patients with tumors harboring BRAF V600E or RAS mutations (4.8% or 11.3%, respectively), or in the high-risk patients defined by the ATA high-risk group or the TNM stage III–IV group (9.1% or 12.9%, respectively),” Dr. Song reported. “Even after adjusting for clinicopathologic cofactors, the presence of TERT promoter mutations significantly increased the risk of both recurrence and thyroid cancer-specific mortality among the ATA high-risk group.”
“TERT promoter mutations strengthened the prognostic predictions of the conventional staging systems,” Dr. Song noted. “Genetic screening for TERT promoter mutations could aid predictions of mortality and recurrence in DTC patients, particularly high-risk patients.”
- See more at: http://www.cancernetwork.com/ata-2015-thyroid-cancer/tert-braf-mutations-deadly-combo-thyroid-cancer-patients#sthash.tMAHGqTk.dpuf

October 23, 2015

News | October 23, 2015 | ATA Thyroid Cancer 2015, Thyroid Cancer - See more at: http://www.cancernetwork.com/ata-2015-thyroid-cancer/tert-braf-mutations-deadly-combo-thyroid-cancer-patients#sthash.tMAHGqTk.dpuf

By Bryant Furlow

October 23, 2015

Tuesday, October 20, 2015

TSH overcomes BrafV600E-induced senescence to promote tumor progression via downregulation of p53 expression in papillary thyroid cancer

Abstract only:
http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2015253a.html

Tigers' Daniel Norris reveals he has thyroid cancer

http://www.freep.com/story/sports/mlb/tigers/2015/10/19/detroit-tigers-daniel-norris/74236764/

Thursday, October 15, 2015

Is red wine at dinner good for type 2 diabetes?

http://www.cbsnews.com/news/red-wine-at-dinner-may-help-hearts-in-type-2-diabetes/

By Mary Brophy Marcus CBS News October 13, 2015, 1:38 PM

Last Updated Oct 14, 2015 7:10 AM EDT

A glass of red wine each evening with dinner may offer heart health perks to people with type 2 diabetes.

A two-year study published in the Annals of Internal Medicine is the first long-term study aimed at assessing the effects and safety of drinking moderate amounts of alcohol in people with type 2 diabetes, who are more at risk for developing cardiovascular disease than the general population. Those with type 2 diabetes also tend to have lower levels of HDL, the "good" cholesterol.
The researchers from Ben-Gurion University of the Negev reported that over two years, red wine helped improve signs of cardiac health by modestly increasing levels of HDL cholesterol and lowering overall cholesterol.

The randomized controlled intervention trial involved 224 controlled diabetes patients aged 45 to 75, who generally abstained from alcohol. The patients were randomly assigned to drink 5 ounces of red wine, white wine, or mineral water (the control group) with their dinner for two years. They were all given instructions to follow a well-balanced Mediterranean diet plan that did not have a calorie restriction.

The researchers performed genetic tests that showed how quickly the patients metabolized alcohol, as well as various lipid (cholesterol) tests. They also measured glucose control, blood pressure, liver function tests, medication use, and other symptoms at several time points during the two-year follow-up.

Compared with the group that drank water, patients in the red wine group had improvements in their lipid tests, the study showed. "Red wine was found to be superior in improving overall metabolic profiles, mainly by modestly improving the lipid profile, by increasing good HDL cholesterol and apolipoprotein A1, one of the major constituents of HDL cholesterol, while decreasing the ratio between total cholesterol and HDL cholesterol," the researchers explained.

Also, in both wine groups, patients who were "slow alcohol metabolizers" (according to the genetic tests) showed more improvements in glucose control tests than "fast alcohol metabolizers." Compared with water, wine did not increase or decrease blood pressure or liver function tests.
The study authors noted that in both red and white wine drinkers, sleep quality was significantly improved, too, compared with the water control group.

Iris Shai, principal investigator of the trial, and a member of the Department of Public Health in the Faculty of Health Sciences, said in a press statement, "The differences found between red and white wine were opposed to our original hypothesis that the beneficial effects of wine are mediated predominantly by the alcohol."

So, how much can people with type 2 diabetes sip at dinner without going over the top? "One to two glasses of red wine for men and up to one glass of red wine for women, daily, at dinner," was the amount indicated by the study, Dr. Minisha Sood, an endocrinologist at Lenox Hill Hospital, told CBS News.

Sood said researchers have known for some time that moderate amounts of alcohol are acceptable for diabetics, but the jury was out on which kind of alcohol might offer the most benefit.

Sood said of red wine's health-enhancing ingredients: "It's the non-ethanol components of the wine, which are present more so in red wine. It's the phenols, it's the resveratrol, it's the tannins. They all work together with the ethanol possibly to result in these positive changes."

While the study shows benefits, Dr. Susan Spratt, an endocrinologist and assistant professor of medicine at Duke University School of Medicine, said, "I worry about the subset of my type 2 diabetes patients who drink too much, and that this may give them more ammunition to say alcohol is good for diabetes. Over-drinking can poison the pancreas. In these patients, when they stop drinking, their diabetes gets tremendously better."

Spratt also told CBS News that in the South, where she lives, many people abstain from drinking for religious reasons. She said, "Here in the South, it would not be something I would generally recommend. I would not say, 'Now you should start drinking wine.' I wouldn't tell someone to start drinking, but if I knew a type 2 diabetes patient was a moderate drinker, I would tell them it looks like red wine is the best choice out of all alcohols to drink, rather than white wine, beer, or hard liquor."

Spratt also noted that the study did not look at cardiovascular outcomes such as heart attack and stroke.

For 51-year-old Garret Rubin, who said he has to watch out for everything -- fats, salt, sugar -- in his diet since being diagnosed with type 2 diabetes, the study is a positive note.

Rubin said diet, exercise and medication will remain his first line of defense, but he told CBS News, "Now, since I have a choice, I think red wine might be the thing."

Editor's note: In an earlier version of this article, Dr. Sood said red wine decreased development of heart disease, but that was not found in the study. The research only looked at risk factors like cholesterol levels, not whether patients actually developed heart disease.

Friday, October 9, 2015

2015 NCCN Guidelines® for Thyroid Carcinoma Recommend LENVIMA™ (lenvatinib) as Preferred Agent

http://www.prnewswire.com/news-releases/2015-nccn-guidelines-for-thyroid-carcinoma-recommend-lenvima-lenvatinib-as-preferred-agent-300156158.html

WOODCLIFF LAKE, N.J., Oct. 8, 2015 /PRNewswire/ -- Eisai Inc. announced the decision of the National Comprehensive Cancer Network^® (NCCN^®) to recommend LENVIMA™ (lenvatinib) as the preferred agent for the treatment of patients with progressive and/or symptomatic metastatic differentiated thyroid cancer, including papillary, follicular and Hürthle cell thyroid carcinoma, that no longer responds to radioactive iodine therapy in the 2015 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Thyroid Carcinoma. The panel based its recommendation on the response rate seen in the pivotal Phase 3 SELECT clinical trial.

LENVIMA, a receptor tyrosine kinase inhibitor discovered and developed by Eisai, was approved by the U.S. Food and Drug Administration in February 2015 for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC).

The most common types of thyroid cancer, papillary and follicular (including Hürthle cell), are classified as differentiated thyroid cancer (DTC) and account for approximately 95% of all cases. While most DTC patients are curable with surgery and radioactive iodine treatment, the prognosis for those patients whose cancers persist or recur is poor. There are a limited number of treatment options for this radioactive iodine-refractory form of thyroid cancer.

"We are pleased that the NCCN has recommended the use of LENVIMA as the preferred treatment option for patients with progressive and/or symptomatic metastatic differentiated thyroid cancer who have become refractory to radioactive iodine therapy," said RuiRong Yuan, MD, Chief Medical Officer, Eisai Global Oncology Business Unit, and Vice President, Medical Affairs, Americas Region, Eisai Inc. "This decision underscores the role of LENVIMA and provides oncologists and endocrinologists with an evidence-based, consensus-driven guide for decision-making when treating patients with this rare and difficult-to-treat cancer."

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) document provides evidence-based, consensus-driven management to help patients receive preventive, diagnostic, treatment, and supportive services that are most likely to lead to optimal outcomes. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer care—including physicians, nurses, pharmacists, payers, patients and their families—with the ultimate goal of advancing patient care in the fight against cancer.

About LENVIMA™ (lenvatinib)

LENVIMA™ (lenvatinib) is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).

LENVIMA, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. LENVIMA™ (lenvatinib) was approved under Priority Review designation for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer by the FDA in February 2015. Eisai was granted Orphan Drug Designation (ODD) for lenvatinib in various types of thyroid cancer in the United States, Japan, and Europe.

Important Safety Information

Warnings and Precautions

Hypertension reported in 73% of patients on LENVIMA vs 16% for placebo (44% vs 4% ≥grade 3). Blood pressure should be controlled prior to treatment. Withhold dose for grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose when controlled at ≤grade 2. Discontinue for life-threatening hypertension.
Cardiac dysfunction reported in 7% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor for signs/symptoms of cardiac decompensation. Withhold for grade 3 cardiac dysfunction. Resume at reduced dose or discontinue based on severity and persistence of cardiac dysfunction. Discontinue for grade 4 cardiac dysfunction.
Arterial thromboembolic events reported in 5% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Discontinue following an arterial thrombotic event. The safety of resuming LENVIMA after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
ALT and AST increases (≥grade 3) occurred in 4% and 5% of patients on LENVIMA vs 0% for placebo. Across clinical studies in which 1108 patients received LENVIMA, hepatic failure (including fatal events) was reported in 3 patients and acute hepatitis in 1 patient. Monitor liver function before initiation, then every 2 weeks for first 2 months, and at least monthly thereafter during treatment. Withhold dose for liver impairment ≥grade 3. Resume at reduced dose or discontinue based on severity/persistence of hepatotoxicity. Discontinue for hepatic failure.
Proteinuria reported in 34% of patients on LENVIMA vs 3% for placebo (11% vs 0% ≥grade 3). Monitor for proteinuria before and during treatment. Withhold dose for ≥2 grams of proteinuria/24 hours. Resume at reduced dose when proteinuria is <2 discontinue="" for="" gm="" hours.="" li="" nephrotic="" syndrome.="">
Events of renal impairment reported in 14% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Withhold LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced dose or discontinue, depending on severity/persistence of renal impairment.
Events of gastrointestinal (GI) perforation or fistula reported in 2% of patients on LENVIMA vs 0.8% for placebo. Discontinue in patients who develop GI perforation or life-threatening fistula.
QT/QTc interval prolongation reported in 9% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or patients taking drugs known to prolong the QT interval. Monitor and correct electrolyte abnormalities in all patients. Withhold dose for ≥grade 3 QT interval prolongation. Resume at reduced dose when QT prolongation resolves to grade 0, 1, or baseline.
Hypocalcemia ≥grade 3 reported in 9% of patients on LENVIMA (2% for placebo). Monitor blood calcium levels at least monthly and replace calcium as necessary. Interrupt and adjust LENVIMA as necessary. In most cases, hypocalcemia responded to replacement and dose interruption/reduction.
Across clinical studies in which 1108 patients received LENVIMA, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 3 patients. Withhold LENVIMA for RPLS until fully resolved. Resume at reduced dose or discontinue based on the severity and persistence of neurologic symptoms.
Hemorrhagic events occurred in 35% of patients on LENVIMA vs 18% for placebo (2% vs 3% ≥grade 3). The most frequently reported hemorrhagic event was epistaxis (11% grade 1 and 1% grade 2). Discontinuation due to hemorrhagic events occurred in 1% of patients on LENVIMA. There was 1 fatal intracranial hemorrhage case among 16 patients who received LENVIMA and had CNS metastases at baseline. Withhold dose for grade 3 hemorrhage. Resume at reduced dose or discontinue, based on severity/persistence of hemorrhage. Discontinue for grade 4 hemorrhage.
LENVIMA™ (lenvatinib) impairs exogenous thyroid suppression. In patients with a normal baseline TSH, elevation of TSH level above 0.5 mU/L was observed post baseline in 57% of patients on LENVIMA (14% for placebo). Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC.
LENVIMA may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy.

Adverse Reactions

The most common adverse reactions observed in LENVIMA-treated patients vs placebo-treated patients were hypertension (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%), arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%), weight decreased (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs 8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs 3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal pain (31% vs 11%), and dysphonia (31% vs 5%).

Use in Specific Populations

Because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment.
LENVIMA may result in reduced fertility in females of reproductive potential, and may result in damage to male reproductive tissues, leading to reduced fertility of unknown duration.

For more information about LENVIMA, click here for the full Prescribing Information or visit www.LENVIMA.com.

About Eisai Inc.At Eisai Inc., human health care is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer's disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at www.eisai.com/US.

Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey and Pennsylvania, as well as a global demand chain organization that includes facilities in Maryland and North Carolina. Eisai's global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.


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SOURCE Eisai Inc.

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http://www.eisai.com