Clinical Staging For Prostate Cancer May Not Be Effective

A widely used Pinchot CS test aiding the prediction of outcome of most prostate cancer by doctors and patients seems to be worthless according to a new study by a group of researchers which was published in the journal CANCER..
CS is called “clinical stage” since it does not involve the findings of pathologic examination, which is usually the result of microscopic evaluation.
According to the results of research,

Clinical stage was assigned incorrectly in 1370 of 3875 men (35.4%). Errors more commonly resulted in patient downstaging than upstaging (55.1% vs 44.9%; P < .001). Patients with TRUS lesions were more likely to be staged incorrectly than those with abnormal DRE findings (65.8% vs 38.2%; P < .001). Biopsy laterality was found to strongly influence stage assignment. Even after correction of staging errors, there was no association noted between clinical stage and biochemical disease recurrence after radical prostatectomy. 

The researchers conclude that;

Errors in applying clinical staging criteria for localized prostate cancer are common. TRUS findings are frequently disregarded, and practitioners incorrectly incorporate biopsy results when assigning stage. However, staging errors do not appear to account for the inconsistent reliability of clinical stage in predicting prostate cancer outcomes. These findings further challenge the utility of a DRE‐based and/or TRUS‐based staging system for risk assessment of localized prostate cancer.Cancer 2010. © 2010 American Cancer Society.

The complete study is published online ahead of the print edition of the journal Cancer.

Happy Thanksgiving Day! Let Us Look Forward To A Cancer Free World.

Happy Thanksgiving and enjoy the weekend.

Cancer Care In The Developing World, A Pod Cast.

Of all the cancers deaths, as much as three-quarters of the deaths occur in developing countries. These places severely lack the resources needed to prevent, diagnose and treat cancer. As a result WHO and the International Atomic Energy Agency (IAEA) have created a Joint Programme on Cancer Control focusing on the needs of developing countries.
Following is the WHO Podcast by Veronica Riemer where she looks at cancer care in the developing world. She speaks with Dr Margaret Chan, WHO's Director-General, who explains what the IAEA brings to this program and others:
Listen to this episode - duration 07:37 min [mp3 4.4Mb] 

A significant reduction in tumor volumes when different regimens of systemic PI-103 delivery are combined with NSC-derived S-TRAIL

The resistance of glioma cells to a number of anti-tumor agents and the highly invasive nature of glioma cells that escape the primary tumor mass are key impediments to the eradication of tumors in glioma patients. In this study, we evaluated the therapeutic efficacy of a novel PI3-kinase/mTOR inhibitor, PI-103, in established glioma lines and primary CD133+ glioma initiating cells and explored the potential of combining PI-103 with stem cell delivered secretable tumor necrosis factor apoptosis inducing ligand (S-TRAIL) both in vitro and in orthotopic mouse models of gliomas. We show that PI-103 inhibits proliferation and invasion, causes G0-G1 arrest in cell cycle, and results in significant attenuation of orthotopic tumor growth in vivo. Establishing co-cultures of neural stem cells (NSCs) and glioma cells, we show that PI-103 augments the response of glioma cells to stem cell delivered S-TRAIL. Using bi-modal optical imaging, we show that when different regimens of systemic PI-103 delivery are combined with NSC-derived S-TRAIL, a significant reduction in tumor volumes is observed compared to PI-103 treatment alone. To our knowledge this is the first study that reveals the anti-tumor effect of PI-103 in intracranial gliomas. Our findings offer a preclinical rationale for application of novel stem cell-based apoptotic therapies to improve treatment of malignant gliomas.

PUBMED

Amgen's XGEVA™ (denosumab), Gets FDA Approval for Fractures in Cancer Treatment

THOUSAND OAKS, Calif., (Nov. 18, 2010) /PRNewswire/ — Amgen Inc. (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved XGEVA™ (denosumab), the first and only RANK Ligand inhibitor for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. XGEVA was approved following a 6 month priority review by the FDA, a designation reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.

“Today’s approval of XGEVA illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine,” said Kevin Sharer, chairman and chief executive officer of Amgen. “A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers.”

Bone metastases, the spread of cancer to the bones, are a serious concern for patients with advanced cancer and present a considerable burden to the healthcare system. Weakened bones due to metastases can lead to fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation, designed to prevent or manage bone complications. The primary goal of treatment for bone metastases is to prevent the occurrence of debilitating and costly bone complications, which can disrupt a patient’s life and cause disability, pain and hospitalization.

“As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment,” said David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System. “Based on the compelling science and robust clinical evidence seen with XGEVA, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer.”

The RANK Ligand pathway, first discovered by Amgen scientists in the mid-1990s, is believed to play a central role in cancer-induced bone destruction, regardless of cancer type. XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK on the surface of osteoclasts, thereby decreasing bone destruction.

XGEVA Clinical Trial Experience

The FDA approval of XGEVA is based on the results of three pivotal, Phase 3 head-to-head trials that evaluated XGEVA delivered every four weeks as a 120 mg subcutaneous injection versus Zometa® (zoledronic acid) delivered every four weeks via a 15-minute intravenous infusion, adjusted for kidney function per the labeled instructions. The clinical program for XGEVA spanned more than 50 tumor types in over 5,700 patients. In the Phase 3 trials, XGEVA demonstrated a clinically meaningful improvement in preventing SREs compared to Zometa. Specifically, in patients with breast or prostate cancer and bone metastases, XGEVA was superior to Zometa in reducing the risk of SREs. In patients with bone metastasis due to other solid tumors or bone lesions due to multiple myeloma, XGEVA was noninferior (trending towards superiority) to Zometa in reducing the risk of SREs. Superiority was also seen in the integrated analysis of the Phase 3 studies.

Overall rates of adverse events and serious adverse events were generally similar between XGEVA and Zometa. Osteonecrosis of the jaw (ONJ) was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the XGEVA arm. Overall survival and progression-free survival were similar between arms in all three trials.

“As many as 70 percent of patients with prostate cancer that have metastasized to the bone are not currently receiving therapy to prevent complications from these bone metastases. This may be secondary to urologists lacking comfort or facilities to provide infusion treatment,” said Neal D. Shore, M.D., FACS, medical director, Carolina Urologic Research Center. “XGEVA could provide increased treatment care options and accessibility for urologist’s who treat advanced prostate cancer; as XGEVA is administered as a subcutaneous injection on a monthly basis. Also, XGEVA does not require dose adjustment for changes in renal function.”

ECONOMIC IMPACT OF SREs

The total economic burden of patients with bone metastases in the U.S. alone estimated to be $12.6 billion annually.ⁱ Patients who experience an SRE as a result of bone metastases incur significantly higher medical costs compared with those who do not experience such events.^{ii iii iv} In addition, once patients experience an SRE, the risk of a subsequent SRE is increased. The costs of SREs vary by type and severity, ranging from relatively low costs for minor fractures to high cost events like spinal cord compression associated with hospitalization. Studies have shown that the costs of treating SREs are a significant cost burden.

XGEVA is an innovative therapy that significantly reduces debilitating and costly SREs. This can result in cost offsets due to the reduced incidence of SREs and related medical costs. XGEVA will cost $1,650 monthly based on wholesale acquisition cost.

XGEVA FIRST STEP™ COUPON PROGRAM

Amgen is committed to supporting patient access to important medicines through innovative programs including our newly established commercial co-pay program for XGEVA, financial support to independent third party co-pay foundations, and the Safety Net Foundation, which provides free products to uninsured patients who qualify. The XGEVA FIRST STEP™ Coupon Program is a landmark program among oncology commercial co-pay programs, as it is the first program under the medical benefit with no income eligibility requirement. The program is intended to provide assistance to eligible patients who need help meeting their deductible, co-insurance, and/or co-payment requirements under the medical benefit for XGEVA. Under this program, eligible patients will incur no out of pocket costs for their initial XGEVA injection and pay a maximum of $25 for subsequent injections.

XGEVA Regulatory Status

Amgen has also submitted marketing applications for XGEVA in the European Union, Australia, Canada and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi-Sankyo Company, Limited and a marketing application was submitted in August.

XGEVA Important Safety Information

XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

Osteonecrosis of the jaw can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

The most common adverse reactions in patients receiving XGEVA were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving XGEVA was dyspnea. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis and hypocalcemia. Please visit www.amgen.com for full prescribing information.

Denosumab is also marketed as Prolia™ in other indications.

Bone Metastases and SREs: Prevalence and Impact

Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease.^v

Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.^{vi vii viii} Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation.^ix Such events can profoundly disrupt a patient’s life and can cause disability and pain.^{x xi xii}

Denosumab and Amgen's Research in Bone Biology

The denosumab development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials. In addition to this newly approved indication, XGEVA is also being investigated for its potential to delay bone metastases in prostate and breast cancer.

Medicare Open Enrollment Open From November 15 To December 31 2010

Every Year Medicare in the fall, offers new prescription drug and health plan coverage choices and everyone is encouraged to review their plans.
This year the open enrollment is open from November 15 to December 31st 2010. This year there are many differences offered with the new health care law, there are new benefits available including lower prescription costs, wellness check-ups, and additional preventive care services. Medicare.gov has many resources to help you with choices during this Open Enrollment.
Follow the links after the jump (video) for resources to help you with Medicare Open Enrollment.

Where do I start?
How do I choose a Medicare plan?
How can I save money on my medical and drug costs?
How does the new health care law affect my Medicare?
Where can I get personalized help?

Triple-Negative Breast Cancer A Review On Current Concepts.

Tripple Negative Breast Cancer appeared on PubMed, (A medical document archive) somewhere in 2006 and since then it has grown to be about 600 articles. This also shows the interest by oncologists, pathologists, and geneticists, and certainly by the approximately 12 to 17% of women with breast cancer who have triple-negative breast cancer. Triple breast cancer is generally diagnosed based upon the presence, or lack of, three "receptors" known to fuel most breast cancers: estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). The most successful treatments for breast cancer target these receptors.
A triple negative breast cancer diagnosis means that the offending tumor is estrogen receptor-negative, progesterone receptor-negative and HER2-negative, thus giving rise to the name established as "triple negative breast cancer."
There is a Foundation, TNBF (Tripple Negative Breast Cancer Foundation) which  is devoted to finding targeted treatment for triple negative breast cancer. You too can help them as well as download PDF of the Guide to Understanding Triple Negative Breast Cancer,
A team of experts, including Dr. Foulkes at the Program in Cancer Genetics, Departments of Oncology and Human Genetics, Gerald Bronfman Centre for Clinical Research in Oncology, McGill University, have written an article on current concepts on Tripple Negative Breast Cancer with concluded with the following conclusion.
The article is available at NEJM, New England Journal of Medicine and from McGill University.

Histologic and Immunohistochemical
Features of Triple-Negative and Core Basallike
Breast Cancers.

Taken in their entirety, triple-negative and basal like breast cancers show aggressive clinical behavior, but a subgroup of these cancers is markedly sensitive to chemotherapy and is associated with a good prognosis when treated with conventional chemotherapy regimens. Furthermore, some triple-negative and basal-like cancers may harbor a dysfunctional BRCA1 pathway and thus may be sensitive to agents such as platinum salts and inhibitors of the PARP enzyme that selectively target cells deficient in homologous recombination DNA repair. It seems very likely that neither triple-negative nor basal-like breast cancers are single entities but rather are a collection of different diseases. Hence, studies that address the molecular underpinning of this heterogeneity and attempt to identify the drivers of therapeutically relevant subgroups of triple-negative and basal-like breast cancers are warranted.
A diagnosis of triple-negative disease has currently important implications for the choice of systemic therapies. Given the lack of an internationally accepted definition of basal-like breast cancer, it is not surprising that this diagnosis has no clinical implications — especially since a substantive portion of these cancers may be ER-positive or may over express HER2. It could be argued that instead of identifying descriptive and prognostic molecular subgroups (e.g., basal-like and claudin-low) within the triple-negative group, it would be more clinically relevant to identify those patients whose triple-negative tumors are sensitive to specific chemotherapy agents (or combinations thereof) and targeted therapies. The expressions “triple-negative” and “basal-like” are essentially operational rather than diagnostic. In time, they will probably be replaced by other, more specific terminology.