Thursday, February 14, 2013

Drug Shown to Reverse Radioiodine Resistance in Some Advanced Thyroid Cancers

Drug Shown to Reverse Radioiodine Resistance in Some Advanced Thyroid Cancers

Released: 2/13/2013 5:00 PM EST
Embargo expired: 2/13/2013 5:00 PM EST
Source Newsroom: Memorial Sloan-Kettering Cancer Center
Newswise — NEW YORK, FEBRUARY 13, 2013 – The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine (RAI), the most effective therapy for the disease, according to new research from Memorial Sloan-Kettering Cancer Center.
Published in the February 14 issue of the New England Journal of Medicine, the study offers new hope for patients with a disease that can have a poor prognosis. An estimated 56,000 new cases of thyroid cancer are diagnosed each year in the United States, and that number is on the rise, according to the National Cancer Institute. About 5 percent of these patients will eventually develop distant metastatic disease, and the ten-year survival rate for patients with metastatic tumors that fail to respond to RAI is approximately 10 percent.
According to James A. Fagin, MD, Memorial Sloan-Kettering’s Endocrinology Service Chief and senior author on the study, many trials have tested strategies for overcoming RAI resistance in metastatic thyroid cancers, but none have been successful. Previous studies have shown that a cell’s ability to absorb RAI is controlled by the MAPK pathway, so Dr. Fagin and his colleagues examined whether selumetinib, an MAPK inhibitor, could reverse RAI resistance by inhibiting the signaling of genetic mutations in this pathway. The approach proved effective, especially in patients with thyroid cancers that contain a mutation in the RAS gene – a component of the MAPK pathway.
“Blocking this key pathway increased the uptake of iodine, making radioiodine treatment potentially effective once again,” said Fagin, who led this research in cells and in mice.
Following a five-day low-iodine diet, researchers administered selumetinib to 20 patients with tumors resistant to radioiodine. After four weeks, patients underwent a diagnostic scan that measured how much RAI their tumors would absorb. In eight patients, including all five with an NRAS gene mutation, selumetinib increased iodine uptake enough to allow patients to undergo RAI therapy.
Following RAI, five patients had confirmed partial responses and three had stable disease. In seven of the eight patients, outcomes remained unchanged during six months of follow-up. All eight patients had a decreased level of serum thyroglobulin – a protein in the blood used to screen for advanced thyroid cancer – and none experienced serious side effects from selumetinib.
“An advantage of this therapeutic strategy is that only a short course of drug therapy is required to elicit a significant clinical effect,” Fagin said, adding that “the initial results show promise for RAS-mutant disease, but the hope is that a larger trial will shed light on whether selumetinib can be effective for a broader range of advanced thyroid cancer subtypes.”
Memorial Sloan-Kettering will lead the international, multicenter phase III clinical trial of selumetinib later this year. The trial, which will be sponsored by AstraZeneca, will enroll patients who have recently had their thyroid gland removed – a procedure known as total thyroidectomy – due to thyroid cancer that has spread to nearby tissue or lymph nodes.
The current research was supported by grants from the American Thyroid Association, The Society of Memorial Sloan-Kettering Cancer Center, the National Institutes of Health (under award numbers CA50706 and CA72598), AstraZeneca, and Genzyme.
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Memorial Sloan-Kettering Cancer Center is the world’s oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide. For more information, go to www.mskcc.org.

Friday, February 8, 2013

Hand-Foot Syndrome Questions

Hi, Everyone - 

I've gotten a couple emails asking about any over-the-counter products I've found that help with Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia) symptoms.

I wish I had something new to add, but I'm pretty much relying on the old stand-byes I've used for several years now.

The best product I've found for use on both my feet and my hands has been Bag Balm.  It helps with the burning and peeling and helps keep the skin moist.  I find using it at least at bed time and in the morning to be the most effective, or more often if needed.

For some reason, my left heel has always been a bad spot for me.  I've tried various cushions there without a lot of success.  This current cycle, I'm trying some new.  It's Dr. Scholl's P.R.O. Pain Relief Orthotics for Heel.  This seems to be helping quite a bit with the heel pain and blisters I tend to develop there from the H-F Syndrome.  I continue to use Bag Balm there and the combination seems to be working.

I am also continuing with the practice of lightly buffing the H-F Syndrome areas with a pumice stone.  This helps keep the dead skin under control and definitely eases pain in those spots.

Hope these ideas are of some help!

John


 DAIRY ASSN. 176702 Bag Balm 10oz (Google Affiliate Ad)
 

Sorafenib Improves PFS in Thyroid Cancer

Sorafenib Improves PFS in Thyroid Cancer

sorafenib (Nexavar)A phase III trial of sorafenib (Nexavar) in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer met its primary endpoint of a statistically significant improvement in progression-free survival (PFS) compared with a placebo.

Though no data have yet been made available, a joint announcement from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. reported that the results were positive, and detailed efficacy and safety analyses from this study are expected to be presented at a future medical meeting.

The phase III DECISION trial enrolled 417 patients in an international, multicenter, randomized, placebo-controlled study. Patients in the study had locally advanced or metastatic disease and had received no prior chemotherapy, tyrosine kinase inhibitors, monoclonal antibodies that target VEGF or VEGF receptor, or other targeted therapies for thyroid cancer.

The trial was initiated based on a series of positive phase II trials. For example, in the results of a single-arm trial presented at the 2011 annual meeting of the American Society of Clinical Oncology, the median PFS was 93.6 weeks and the median overall survival (OS) was 140.6 weeks in patients with progressing advanced, iodine-refractory differentiated or poorly differentiated thyroid cancer and medullary and anaplastic thyroid carcinoma who received 400 mg of sorafenib twice daily.

“Effective treatment options are urgently needed for patients with RAI-refractory differentiated thyroid cancer,” said Dimitris Voliotis, MD, vice president of Global Clinical Development Oncology for Bayer HealthCare, in a statement. “We are pleased that the results of this study demonstrate that Nexavar may provide a treatment option for these patients.”

Only a small number of drugs have been approved to treat thyroid cancer. Most recently, cabozantinib (Cometriq) was approved to treat patients with medullary thyroid cancer, and vandetanib (Caprelsa) was also approved for this indication in 2011. In the statement, Bayer noted that the results of this study would be used as the basis for marketing authorization of sorafenib in the treatment of patients with RAI-refractory differentiated thyroid cancer.

Cancer centers collaborate to talk about TKI therapy in thyroid cancer | Endocrinology

Interesting - the drug I'm on (Sutent) is a TKI.  I didn't realize they were being used for Thyroid Cancer outside of clinical trials.  I wonder how insurance handles it?

 

Cancer centers collaborate to talk about TKI therapy in thyroid cancer

Carhill AA. J Clin Endocrinol Metab. 2013;98:31-42.

  • January 15, 2013
Researchers from Baylor College of Medicine and The University of Texas MD Anderson Cancer Center collaborated recently to discuss the clinical use of tyrosine kinase inhibitors in thyroid cancer patients. Their review of the institutions’ approach was published in the Journal of Clinical Endocrinology and Metabolism.
“The recommended use of tyrosine kinase inhibitor (TKI) therapy outside of clinical trials in patients with progressive thyroid cancer as well as the recognition by the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and the Oncology Nursing Society (ONS) of the necessity for standardized approaches to patients receiving these biological agents have highlighted the need for guidance to prescribing physicians to improve patient safety and monitoring and to promote consistency and compliance with both institutional and industry standards,” researchers wrote.
According to the paper, TKIs that target angiogenesis and other tumor-promoting functions have yielded influential clinical findings in both differentiated thyroid cancer and medullary thyroid cancer.
Therefore, researchers in the department of endocrine neoplasia at the MD Anderson Cancer Center identified which patients should be placed on TKI therapy before initiation by conducting a review of medical history, laboratory data and performance status.
“Due to the duration of treatment, the potential for toxicities, and the need for regular monitoring, the importance of a detailed discussion and obtaining written informed consent from the patient before initiation of TKI therapy cannot be stressed enough,” researchers wrote.
The standards for oral TKI use in patients with thyroid cancer by this institution include: general practice standards, patient information/education, documentation and monitoring.
However, they advise clinicians to be aware of pharmaceutical-specific assistance programs for patients due to the expensive nature of the therapy.
“We believe that by using these tools, we will improve patient safety and monitoring, promote consistency among providers, and ensure compliance with consensus-derived safety standards for prescribing oral chemotherapy,” the researchers concluded.
Disclosure: Several researchers report financial ties with AstraZeneca, Bayer and Pfizer

The Meaning of Thyroglobulin Levels for Thyroid Cancer Survivors

The Meaning of Thyroglobulin Levels for Thyroid Cancer Survivors
Sunday, 20 January 2013 11:23
Thyroglobulin, also known as "Tg", is a prohormone (protien) that is produced by thyroid cells or thyroid cancer cells and released into the blood.  Thyroglobulin can be measured with a simple blood test.  The detection of thyroglobulin is proof of the presence of thyroid cells.  This test is very useful when monitoring thyroid cancer patients after surgery and radioactive iodine-131 ablation treatment.  


For thyroid cancer survivors the goal is to have a stable very low thyroglobulin or undetectable level of thyroglobulin.  This would indicated no thyroid cancer cells.
    
It is also important that one's thyroglobulin levels don't increase over time.  If one's thyroglobulin levels do increase over time this could indicate a recurrence or metastasis of one's thyroid cancer.
     
Below is the percentage of recurrence within five years after radioactive Iodine-131 ablation for differentiated thyroid carcinoma in one study conducted by Kloos and Mazzaferri.
   
Thyroglobulin (Tg) less than .5 ng/ml        = 1.6% recurrence of thyroid cancer5
Thyroglobulin (Tg) 0.6 to 2.0 ng/ml           = 5.5% recurrence of thyroid cancer5
Thyroglobulin (Tg) greater than 2.0 ng/mL = 80% recurrence of thyroid cancer5
            
It is recommended that thyroid cancer survivors thyroglobulin levels be monitored every 6 to 12 month to detect recurrences or metastasis of thyroid cancer.

    
Reference:
5.  Kloos RT, Mazzaferri El, A Single Recombinant Human Thyrotropin-Stimulated Serum Thyroglobulin Measurement Predicts Differentiated Thyroid Carcinoma Metastases Three to Five years Later. Endocrinology Metabolism 2005, 90:1440
Last Updated on Sunday, 20 January 2013 11:44

Dr. Yuri Nikiforov on the Genetic Evolution of Thyroid Cancer

Dr. Yuri Nikiforov on the Genetic Evolution of Thyroid Cancer