Ibrutinib and Rituximab for Untreated CLL: ‘Practice Changing’


The combination of ibrutinib (Imbruvica, Pharmacyclics/Janssen) and rituximab (Rituxan, Roche/Genentech) beat the current gold standard of fludarabine, cyclophosphamide, and rituximab (FCR) for young, fit patients with untreated chronic lymphocytic leukemia (CLL) in a large trial funded by the National Cancer Institute (NCI).

Ibrutinib plus rituximab showed superior progression-free survival (PFS) and overall survival (OS) compared with FCR, and was also less toxic.

Tait D. Shanafelt, MD

These results from the E1912 study were presented here at the American Society of Hematology (ASH) 2018 Annual Meeting.

“These findings have immediate practice-changing implications and establish ibrutinib as the single most effective first-line therapy for patients with CLL,” lead author Tait D. Shanafelt, MD, from Stanford University, California, told Medscape Medical News.

“These definitive results show why large trials like this that test new therapies in an effort to achieve clinically meaningful benefit for patients are so important,” said Richard F. Little, MD, of the Cancer Therapy Evaluation Program at NCI in a statement.

Shifting Landscape

How these new findings fit alongside other recent results with ibrutinib in CLL is now a matter for consideration.

As reported by Medscape Medical News, data from another large NCI-sponsored trial, the ALLIANCE study, also presented at ASH, showed that ibrutinib alone was superior to the combination of bendamustine-rituximab in elderly patients ≥ 65 years of age with CLL. The investigators concluded that ibrutinib alone is appropriate as initial treatment of CLL in this patient population.

Additionally, results from an industry-sponsored study, the phase 3 iLLUMINATE trial — also presented at ASH (abstract 691) and submitted for approval of an additional indication — showed that the combination of ibrutinib and obinutuzumab (Gazyva, Roche/Genentech) provided a 77% reduction in risk of progression or death compared with chlorambucil and obinutuzumab (HR: 0.23; 95% CI: 0.15 – 0.37; P < .0001).

Aaron T. Gerds, MD

So three trials presented at the meeting suggest, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard for CLL. How are clinicians to choose between these regimens when treating patients with CLL?

“This is an embarrassment of riches,” commented Aaron T. Gerds, MD, of the Cleveland Clinic Taussig Cancer Institute, Ohio, who moderated an ASH press briefing during which the new results were discussed.

Ultimately, clinicians will have to weigh all the factors before deciding on the choices before them, he observed.

He also said that E1912 and ALLIANCE, large cooperative group studies, are important and unbiased, adding they are trials that industry is not likely to conduct. The iLLUMINATE study is industry sponsored and supports a US Food and Drug Administration (FDA) label — another way to pursue a treatment option, he pointed out.

Shanafelt pointed out although the E1912 study is not industry sponsored, it is registered with and has endpoints approved by the FDA. The study met all its endpoints, he noted, and hopes this new partnership between the cooperative groups and the FDA will get a nod for non-industry sponsored treatment options.

With ibrutinib approved as a single agent to treat newly diagnosed CLL, the E1912 study is the first trial in younger patients in which an ibrutinib regimen (ibrutinib plus rituximab) was compared with the gold-standard FCR regimen, and shows that for most patients an ibrutinib regimen should be preferred, lead author Jennifer A. Woyach, MD, of the ALLIANCE study, told Medscape Medical News.

“With these data it is probably appropriate to treat patients with either ibrutinib or the combination of ibrutinib and rituximab,” said Woyach, who is at Ohio State University Comprehensive Cancer, Columbus.

After the ASH meeting, practicing clinicians are likely to offer ibrutinib monotherapy first-line to treatment-naive CLL patients, commented Kanti R. Rai, MD, from the Feinstein Institute of Medical Research at Hofstra/Northwell, Hempstead, New York.

“It is a game changer,” he said and added that physicians are experienced with and comfortable using ibrutinib.

Rai believes data from the ALLIANCE study are more likely to inform clinical practice and ibrutinib monotherapy will be the standard in treatment-naive CLL. “Physicians, patients, and society have become sensitive to the cost of therapy, and with single-agent ibrutinib one is likely to avoid unnecessary expense,” he said.

“The age group difference [younger versus older] between E1912 and ALLIANCE is not likely to be critical,” Rai observed.

“We do not know for sure whether the data from ibrutinib-rituximab versus ibrutinib in older patients [ALLIANCE population] is generalizable to the entire CLL population, and I do not believe this comparison will ever be repeated in younger patients, so I think it is probably reasonable to choose either ibrutinib alone or in combination with rituximab in younger patients,” Woyach told Medscape Medical News.

Shanafelt indicated that the ongoing FLAIR trial is likely to provide a more definitive answer. FLAIR, which is enrolling patients with treatment-naive CLL aged 18 to 75 years, is evaluating four treatment regimens: FCR, ibrutinib-rituximab, ibrutinib-venetoclax, and ibrutinib alone.

Both Rai and Woyach predict that FCR will be used less but is appropriate for certain patients, such as those with mutated IGVH disease (low risk). “Long-term data from the FCR studies shows that a proportion of low-risk patients have the potential for very long-term remission and even cure. We will have to see with long-term follow-up from the E1912 study whether ibrutinib-rituximab is superior to FCR in IGVH mutated patients because that is not clear at this time,” Woyach said.

Shanafelt told Medscape Medical News that both E1912 and ALLIANCE are cooperative group studies and were designed simultaneously prior to the approval of ibrutinib (in 2014). E1912 was conducted in patients ≤ 70 years of age and ALLIANCE in those ≥ 65 years of age. “There was an intentional overlap because some patients have robust health and can tolerate FCR,” he said. “Both trials met their endpoint at the same time and based on the age category, ibrutinib-based therapy is the most effective compared with the best historic regimens,” he said.

“For all comers independent of age, ibrutinib-based treatment is the standard of care based on data from the two studies,” Shanafelt told Medscape Medical News.

The E1912 Study Results

The E1912 trial was a randomized phase 3 study that enrolled 529 patients (2:1) to ibrutinib plus rituximab (n = 354) or standard FCR therapy (n = 175). Patients enrolled were ≤ 70 years of age and those with 17p deletion were excluded because of poor disease response to FCR.

Patients treated with the combination of ibrutinib and rituximab received ibrutinib daily on days 1-28 for each cycle until disease progression or unacceptable toxicity. Rituximab was given in cycles 1-7. Patients in the FCR group were given the drugs over 6 cycles, as is typical in clinical practice.

Median age of patients was 58 years and 41% were ≥ 60 years; 75% of patients had IGVH unmutated disease.

Results were presented for the first interim analysis performed September 2018. Median follow-up was 33.4 months.

For the primary endpoint of PFS, the combination of ibrutinib and rituximab was associated with a 65% reduced risk for progression or death (hazard ratio [HR], 0.35; 95% CI, 0.22 – 0.5; P < .00001). Three-year PFS was 89% for the ibrutinib-rituximab combination and 73% for FCR.

OS was also superior for the combination of ibrutinib and rituximab (HR, 0.17; 95% CI, 0.05 – 0.54; P < .0003).

The superiority of the combination of ibrutinib and rituximab was seen regardless of age, performance status, disease stage, or presence or absence of del11q23. The superiority was also established for IGVH unmutated but not IGVH mutated disease.

Grade 3/4 treatment-related adverse events were reported for 58% and 72% of patients receiving the ibrutinib regimen and FCR, respectively. Compared with ibrutinib plus rituximab, FCR was associated with a significantly higher incidence of grade 3/4 neutropenia (22.7% vs 43.7%), anemia (2.6% vs 12.0%), thrombocytopenia (2.9% vs 13.9%), and infectious complications (7.1% vs 19.0%).

Canada Says Talc May be ‘Harmful to Human Health’


The government of Canada is considering measures that would prohibit or restrict the use of talc in some products. After reviewing the latest science and producing a draft screening assessment, the government “proposes that inhaling loose talc powders and using certain products containing talc in the female genital area may be harmful to human health.”

The announcement was made Wednesday on the Health Canada website.

The draft screening assessment will be published in the Canada Gazette, Part I, and will be open for public comment for 60 days, until February 6, 2019. The Risk Management Scope , which outlines the possible measures to manage the risks identified in the draft screening assessment, will also be open for public comment for the same 60-day period.

The final screening assessment and risk management approach will take into consideration any comments and new evidence received during the consultation period, the announcement notes.

No action, such as warning labels or a ban, will be taken until this final assessment is published, according to news reports.

The document notes that the draft assessment did not identify human health risks of concern from oral exposures, including talc in food and drugs; dermal exposures such as the application of talc-containing products to skin; or inhalational exposures from dry hair shampoo or pressed powder products, such as cosmetics like eye shadow and blush.

However, the assessment did identify two exposure scenarios of potential concern to human health.

One was inhalation of fine particles of talc during the use of loose powder, self-care products (eg, body powder, baby powder, face powder, foot powder), potentially resulting in damage to the lungs.

The other scenario of concern was exposure of the female perineal area, which includes the genitals, to self-care products containing talc (eg, body powder, baby powder, diaper and rash creams, genital antiperspirants and deodorants, body wipes, bath bombs), as this type of exposure has been associated with ovarian cancer in studies of the human population, the document notes.

Move Comes Amid Great Controversy, US Lawsuits

The move from Canada comes amid a growing controversy, as well as fiercely fought court battles in the United States, over whether use of talc in the female genital area contributes to ovarian cancer.

The controversy is over whether talc itself is a carcinogen, and the issue is complicated because talc is sometimes contaminated with asbestos (the two sometimes occur naturally together).

The scientific community has not reached a consensus.

A recent review appearing in the European Journal of Cancer Prevention ( Eur J Cancer Prev. 2008;17:139–146.) concludes that “data collectively do not indicate that cosmetic talc causes ovarian cancer.” The heterogeneity in the perineal dusting studies has raised important concerns over the validity of the exposure measurements, and the lack of a consistent dose–response effect limits making causal inferences. Perhaps more importantly, it is unknown whether external talc dust enters the female reproductive tract, and measures of internal talc exposure such as talc-dusted diaphragms and latex condoms show no relationship with ovarian cancer risk. Talc is not genotoxic, and mechanistic, pathology and animal model studies have not found evidence for a carcinogenic effect, the journal adds.

However, a recent review in Epidemiology ( Epidemiology. 2018;29:41–49 ), concluded that “in general, there is a consistent association between perineal talc use and ovarian cancer.” This was based on a meta-analysis of observational studies that included at least 50 cases of ovarian cancer, and looked at 24 case–control studies (13,421 cases) and three cohort studies (890 cases, 181,860 person-years).

In the US, thousands of lawsuits have been filed by individuals, or the families of deceased individuals, alleging that ovarian cancer was caused by the use of talc products such as Baby Powder and Shower-to Shower manufactured by Johnson & Johnson. The company is reported to be facing more than 10,000 plaintiffs.

Many of the lawsuits that have already taken place have found for the plaintiffs, but not all.

For example, a jury in Missouri ordered Johnson & Johnson to pay $72 million in damages to the family of Jacqueline Fox, who died from ovarian cancer. However, in two cases juries on appeal overturned multimillion dollar awards: Gloria Ristesund of South Dakota was originally awarded $55 million in 2016, but in June the verdict was overturned. In August 2017, a jury in Los Angeles awarded $417 million to Eva Echeverria, but that verdict was overturned 2 months later.

A lawsuit in October 2018 involving a New Jersey woman cleared Johnson & Johnson of liability in a case of mesothelioma and the company’s baby powder product.

In one of the most recent cases, Johnson & Johnson was ordered in July to pay $4.7 billion to 22 women and their families, who claimed that asbestos in the company’s talc products led them to develop ovarian cancer.  The company said the verdict was ‘fundamentally unfair’ and says that its talc products do not contain asbestos.

Talc–Asbestos Connection Explained 

Talc is a naturally occurring mineral, mined from the earth, composed of magnesium, silicon, oxygen, and hydrogen, explains the Food and Drug Administration. It also notes that asbestos, another naturally occurring silicate mineral, may be found in close proximity in the earth, and so mining sites should be selected carefully. “Unlike talc, however, asbestos is a known carcinogen,” the agency notes.

The FDA says that “it continues to investigate and monitor reports of asbestos contamination in certain cosmetic products,” and notes that talc is used in many cosmetic products, including baby powder and makeup such as powder blush and eye shadow.

The American Cancer Society explains that asbestos does sometimes occur naturally in talc, but guidelines issued in the US in 1976 called for the removal of asbestos from commercial talc products.

However, many consumer groups note that this is an area that is not officially regulated, and report that makeup products sold in the United States that have been found to contain asbestos/talc. Consumer groups also point out that talc in cosmetics has been removed by the European Union, but is still allowed in the United States.

The American Cancer Society also emphasizes that it is important to distinguish between the two. Talc that contains asbestos is generally accepted as being able to cause cancer if it is inhaled. However, the evidence about asbestos-free talc is less clear, it notes.

It also cites the conclusions made by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO).

The IARC classifies talc that contains asbestos as “carcinogenic to humans.”

Based on the lack of data from human studies and on limited data in lab animal studies, IARC classifies inhaled talc not containing asbestos as “not classifiable as to carcinogenicity in humans.”

As there is limited evidence from human studies showing a link to ovarian cancer, IARC classifies the perineal (genital) use of talc-based body powder as “possibly carcinogenic to humans.”

The US National Cancer Institute says that the “the weight of evidence does not support an association between perineal talc exposure and an increased risk of ovarian cancer. ”

Breakthrough Therapies in Cancer: CAR T-Cell Therapies


With each passing day, we inch closer to curing cancer.

Until now, the cancer treatment universe was limited to 4 modalities, namely Surgery, Radiation, Chemotherapy and Targeted Drug Treatments. Recently, we have witnessed the addition of a fifth front in the battle against cancer, called Immunotherapy.

In Immunotherapy, scientists have been trying to develop ways to train the human immune system to fight and kill cancer-cells, just like they kill germs in trivial disorders such as the common cold. This technique of harnessing the immune system, is called “Adaptive Cell Transfer” or ACT.

CAR T-Cell Therapies have emerged as the most promising form of Immunotherapy.

What are CAR T-cell Therapies?

When we get sick with the common cold, our immune system attacks the infectious germs and kills them, effectively curing us. What is at work here are a type of cells present in our blood called T-cells. T-cells have the unique ability to identify affected cells, latch on to them and kill them.For a long time, cancer researchers have wondered if it’s possible to train our immune system to kill cancer cells the same way, and effectively become cancer-free. This field of study, titled ‘Immunotherapy’ has been widely researched, and Chimeric Antigen Receptor (CAR) T-Cell Therapies are one of the most exciting advancements in this field.

In a CAR T-cell therapy, a patient’s T-cells are genetically engineered, so that they attach themselves to cancer cells and kill them. More specifically, such T-cells are extracted from the patient’s own blood. These cells are then engineered in a lab to identify specific proteins (or antigens) present within cancer cells, and then these cells are injected back into the patient’s bloodstream.

Many scientists refer to CAR T-Cell Therapies as ‘Living Drugs’ because they constantly attach cancer cells, thereby reducing the rates of recurrence/relapse significantly.

The National Cancer Institute recently issued a simple graphical representation of such therapies on their Twitter feed:
Additionally, the Dana-Farber Cancer Institute has published a video explaining how CAR T-Cell Therapies work:

Current Status of Car T-Cell Therapies

The use of Car T-cell therapies has been limited to clinical trials so far. In these trials, many patients in advanced stages of cancer have experienced positive effects. Many such trials involved patients suffering from advanced ALL (Acute Lymphoblastic Leukemia) with limited treatment options. Most patients experienced 100% remission, and many of them remained in remission for prolonged periods of time.Similar promising results have been observed in the case of lymphoma patients. For patients with ALL, the first line of treatment is usually chemotherapy, followed by a bone marrow transplant. But if the cancer relapses, the treatment options get increasingly thin, close to none. CAR T-cell Therapies act as breakthrough treatments in such cases. So far, the clinical trials have shown positive results. In a trial conducted at the Children’s hospital of Philadelphia (CHOP), 27 out of 30 patients, showed all signs of cancer disappear completely.

Latest Developments

  • The United States FDA has recently approved CAR T-cell therapies for a subtype of ‘B’ cell Acute Leukemias in children (Kymriah) and another one for refractory ‘B’ cell Lymphomas in adults (Yescarta).
  • In another trial conducted on ALL patients at the Memorial Sloan Kettering Cancer center, 14 out of 16 patients demonstrated total recovery, some of them as early as 2 weeks into the treatment.

Potential Side Effects, Toxicity and Management

While the side-effects of such treatments can be life-threatening, the medical fraternity has developed sustainable safeguards against such effects, with supportive treatments. Some of these side effects are listed below:

  1. Cytokine Release Syndrome (CRS) – CRS may cause high fevers, low blood pressure or poor lung oxygenation. Some patients experience delirium, confusion and seizure while undergoing treatment. Such symptoms typically appear within the first week of treatment, and are usually reversible.
  2. Tumour Lysis Syndrome (TLS) – TLS includes a group of metabolic complications that can occur due to the breakdown of dying cells, usually at the onset of toxic cancer treatments. However, TLS can occur a month or more after CAR T-cell therapy. TLS can be a life-threatening complication arising from any treatment that causes cancer cells to break down, including CAR T-cells. This complication has been managed by standard supportive therapy.
  3. B-cell Aplasia – Since T-cells are targeted against surface receptors of B-cells, the normal B-cells also get dystroyed by them. However, no significant or long term side effects have been recorded.

In addition to these side effects, ScienceDirect.com has published a summary of various clinical trials conducted in the field, highlighting their effectiveness in hematologic disorders as compared to results in cases of solid tumors.

For solid tumours, there are a few challenges such as higher risk of major complications and a difficult tumour microenvironment for these cells to be effective. But these hurdles are surmountable, and we will eventually witness better results with this revolutionary approach.
-Dr Amit Jotwani (Co-founder, Onco.com and Senior Consultant Oncologist)

What’s Next in CAR T-cell Therapies?

CAR T-cell therapies seem to have a lot of potential, but further research is needed to make them mainstream and available to patients globally. Many labs around the world are currently testing these therapies, not just for blood cancer but also for solid tumors such as pancreatic and brain cancers. Given the amount of interest the field has generated among researchers worldwide, it is likely that the next decade will be transformative in defining the cancer treatment paradigm.

Watch the video. URL:https://youtu.be/OadAW99s4Ik

References:

1. LLS.org – Article on Chimeric Antigen Receptor T-Cell Therapies
2. ESMO.org – The Evolving Field Of CAR T-Cell Therapies
3. Nature.com – CAR T-Cell Therapies Journal
4. Cancer.gov – The National Cancer Institute’s take on CAR T-Cell Therapies
4. ScienceDirect.com – Toxicity & Management in CAR T-Cell Therapy

National Cancer Institute Quietly Confirms Cannabis Can Cure Cancer


During hearings on marijuana law in the 1930’s, they made claims about marijuana’s ability to cause men of color to become violent and solicit sex from white women. This imagery became the backdrop for the Marijuana Tax Act of 1937 which effectively banned its use and sales.

However, with so much information coming out about the medical value of marijuana and that marijuana is not as dangerous as alcohol, National Cancer Institute took the initiative of finding out whether marijuana does have medical properties in it.

However, it’s downright comical how the government doesn’t bat an eyelid to the more severe mishappenings in the society but find it absolutely justifiable to lock marijuana growers and buyers for cheap labors and locking them up. This destroyed a lot of families.

Marijuana is still illegal in many countries in-spite of not falling under the SCHEDULE 1 rating. Schedule 1 includes drugs which are dangerous, addictive and don’t hold any medical merit. Under NCI (national cancer institute) cannabis, cannabis decrease the hurtful side-effects of chemo and also as a drug to enhance chemo.

Other than this, there have been cases all around the world where they use cannabis to treat and cure cancer. In spite of all this, the government and media yet disagree on bringing the reality to light.

NCI On Marijuana And Its Anti-Tumour Activity

Experiments were conducted on mice and rats which showed that cannabinoids help in resisting inflammation of the colon and may help in reduction of colon cancer-causing cells. It was also helpful in preventing the growth of blood vessels which would help a tumor grow. Study of cannabidiol also showed the death of cancer cells which have a very little effect on normal breast cells. It also showed that cannabinoids helped in lessening the growth of cancer cells and also prevented it from studying.

Increasing The Appetite Of Cancer Patient:

Delta-9-THC and other cannabinoids are some of the best drugs to increase the food intake capacity of cancer patients.

Cannabis For Pain Relief:

Molecules that bind cannabinoid are called cannabinoid receptors have been studied for anti-inflammatory tests. They help relieve the pain of spinal cord, brain and nerve endings.

It is funny how our government runs. Maybe its priorities aren’t in place. What else can we say when the government approves the circulation of Oxycontin in our society. Oxycontin is an extremely addictive drug which gives to 11-year-old kids for a painkiller.

Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.


Abstract

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m2; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712).

Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control group in the EGFR FISH-positive subpopulation, progression-free survival did not differ between treatment groups (hazard ratio [HR] 0·92, 95% CI 0·75-1·12; p=0·40; median 5·4 months [95% CI 4·5-5·7] vs 4·8 months [3·9-5·5]). After 570 deaths in the cetuximab group and 593 in the control group, overall survival did not differ between the treatment groups in the entire study population (HR 0·93, 95% CI 0·83-1·04; p=0·22; median 10·9 months [95% CI 9·5-12·0] vs 9·2 months [8·7-10·3]). In the prespecified analysis of EGFR FISH-positive subpopulation with squamous cell histology, overall survival was significantly longer in the cetuximab group than in the control group (HR 0·58, 95% CI 0·36-0·86; p=0·0071), although progression-free survival did not differ between treatment groups in this subgroup (0·68, 0·46-1·01; p=0·055). Overall survival and progression-free survival did not differ among patients who were EGFR FISH non-positive with squamous cell histology (HR 1·04, 95% CI 0·78-1·40; p=0·77; and 1·02, 0·77-1·36; p=0·88 respectively) or patients with non-squamous histology regardless of EGFR FISH status (for EGFR FISH-positive 0·88, 0·68-1·14; p=0·34; and 0·99, 0·78-1·27; p=0·96; respectively; and for EGFR FISH non-positive 1·00, 0·85-1·17; p=0·97; and 1·03, 0·88-1·20; p=0·69; respectively). The most common grade 3-4 adverse events were decreased neutrophil count (210 [37%] in the cetuximab group vs 158 [25%] in the control group), decreased leucocyte count (103 [16%] vs 74 [20%]), fatigue (81 [13%] vs 74 [20%]), and acne or rash (52 [8%] vs one [<1%]). 59 (9%) patients in the cetuximab group and 31 (5%) patients in the control group had severe adverse events. Deaths related to treatment occurred in 32 (6%) patients in the cetuximab group and 13 (2%) patients in the control group.

Although this study did not meet its primary endpoints, prespecified subgroup analyses of patients with EGFR FISH-positive squamous-cell carcinoma cancers are encouraging and support continued evaluation of anti-EGFR antibodies in this subpopulation.

National Cancer Institute and Eli Lilly and Company.

National Cancer Institute: 90% of population unaware that alcohol causes cancer


Image: National Cancer Institute: 90% of population unaware that alcohol causes cancer

Is it really that surprising that most Americans are unaware that booze causes cancer? Alcohol is often painted with a very positive brush, and is a prominent feature of our own society as well as of other societies across the globe.

Despite being widely consumed and readily available, approximately nine out of 10 people do not know that there are many established links between alcohol and cancer. Alcohol is considered a carcinogen, and has been linked to seven different types of cancer. Alcohol is not just a drug, but is also a poison that contributes to 88,000 deaths every year. The CDC reports that about 1,600 deaths are directly related to alcohol poisoning. Conversely, there has never been a reported overdose death that was related to cannabis.

In fact, cannabis is less harmful than alcohol in just about every single way. Alcohol causes brain damage, while studies show that cannabis can actually help prevent alcohol-related brain damage. Alcohol use is clearly related to a number of different cancers. Marijuana Policy Project notes that several different studies have shown that cannabis use can help reduce the risk of certain cancers. Cannabis use has even been associated with a lower risk of lung cancer. And despite the government claims that it contributes to head and neck cancers, studies have shown that such claims are actually the opposite of reality.

In addition to not being associated with cancer, cannabis is not associated with other health problems either. Alcohol, on the other hand, is tied to many other conditions. For example, alcohol can damage your heart, liver and pancreas. Damage can be incurred after even just one occasion of binge drinking – never mind what will happen to these organs after many binge drinking episodes.

Studies have shown that in addition to being linked to a variety of health problems, alcohol is also far more addictive than cannabis. MPP reports:

“According to a 1998 report by Drs. Jack E. Henningfield of the National Institute on Drug Abuse (NIDA) and Neal L. Benowitz of the University of California at San Francisco, alcohol’s addiction potential is significantly greater than that of marijuana based on a number of indicators.”

The organization also writes that even federal studies have found that marijuana has a very low potential for addiction, and that it is significantly less addictive than other substances, including legal drugs such as alcohol and nicotine. That’s right; even the federal government has concluded that marijuana is less addictive than booze and cigarettes!

If marijuana is less harmful and less addictive than alcohol, then why is it still illegal?

National Cancer Institute and JAMA Medical Journal Admit: “Oops… It Wasn’t Cancer After All”


After decades of wrongful cancer diagnoses and treatments, and millions harmed, the National Cancer Institute and high gravitas journals like JAMA (the Journal of the American Medical Association) finally admit they were wrong all along.

The National Cancer Institute Admits ''Oops... It Wasn't Cancer After All''

Back in 2012, The National Cancer Institute convened an expert panel to evaluate the problem of cancer’s misclassification and subsequent overdiagnosis and overtreatment, determining that millions may have been wrongly diagnosed with “cancer” of the breast, prostate, thyroid, and lung, when in fact their conditions were likely harmless, and should have been termed “indolent or benign growths of epithelial origin.” No apology was issued. No major media coverage occurred. And more importantly, no radical change occurred in the conventional practice of cancer diagnosis, prevention, or treatment.

Essentially, in one sleight of the semantic hand, entire swaths of the U.S., and global population, who thought they had “lethal cancer,” and were subsequently treated for it, often with violent procedures and treatments, were being told that“oops… we got that wrong. You never had cancer after all.”

If you look at the problem through just breast cancer overdiagnosis and overtreatment in the U.S. over the past 30 years, it has been estimated that approximately 1.3 million women were wrongly treated. Most of these women still have no idea they were victims, and many have identified with their “aggressors” in Stolkholm syndrome like fashion, because they think their “lives were saved” by unnecessary treatment, when in fact the side effects, both physical and psychological, have almost certainly reduced both the quality and duration of their lives.

When the National Cancer Institute report was released, it was a sort of vindication for those of us who had been advocating the position that a commonly diagnosed form of so-called “early breast cancer” known as ductal carcinoma in situ was in fact not inherently malignant and should not have warranted the conventional treatments of lumpectomy, mastectomy, radiation, and chemotherapy. I based this position on available research on the natural history of DCIS, and the extremely high survival rates from DCIS, as well as the fact that breast cancer-related mortality had not declined in pace with the expansion of so-called “zero” or “early stage” cancers detected through mammography screenings, as would be expected if these diagnoses actually represented harmful clinical entities.

Since then, I have watched the problem of overdiagnosis and overtreatment closely. I get daily updates from pubmed.gov on the topic, and increasingly, high impact and gravitas journals are reporting on this highly concerning phenomenon. Particularly relevant is a review published late last year, which I reported on in my article titled, “Astounding Number of Medical Procedures Have No Benefit, Even Harm – JAMA Study.”

The JAMA study found that a wide range of standard medical procedures and interventions that millions are subjected to annually, are not evidence-based, as commonly assumed, and have little to no benefit, and may even be causing significant harm. As a result, I now believe that good medicine often involves doing as much as nothing as possible. I also think that people should be aware that any conventional cancer diagnosis has the ability to exert lethal harm via thenocebo effect, regardless of its accuracy (i.e., even a misdiagnosis can result in lethal consequences because the power of belief).

Thyroid Cancer Epidemic Caused by Misinformation, Not Cancer

Another topic I have been trying to spread awareness about is thyroid cancer overdiagnosis and overtreatment. When I first reported on this two years ago in my article, Thyroid Cancer Epidemic Caused by Misinformation, Not Cancer, a series of compelling studies from around the world revealed that the rapid increase in diagnoses in thyroid cancer reflected their misclassification and misdiagnosis. As was the case with screening detected breast and prostate “cancers,” and even many ovarian “cancers,” the standard of care often required the removal of the organ, as well as irradiation and chemotherapy — two interventions known to promote not inhibit cancer.

As is typical of research that undermines the conventional standard of care, there has been little reporting on the topic. That is, until now.

On April 14th 2016, in an article titled “Its Not Cancer: Doctors Reclassify a Thyroid Tumor,” the New York Times reported on a new study published in JAMA Oncology which should forever change the way we classify, diagnosis and treat a common form of “thyroid cancer”:

An international panel of doctors has decided that a type of tumor that was classified as a cancer is not a cancer at all.

As a result, they have officially downgraded the condition, and thousands of patients will be spared removal of their thyroid, treatment with radioactive iodine and regular checkups for the rest of their lives, all to protect against a tumor that was never a threat.

Their conclusion, and the data that led to it, was reported Thursday in the journal JAMA Oncology. The change is expected to affect about 10,000 of the nearly 65,000 thyroid cancer patients a year in the United States. It may also offer grist to those who have been arguing for the reclassification of some other forms of cancer, including certain lesions in the breast and prostate.

The reclassified tumor is a small lump in the thyroid that is completely surrounded by a capsule of fibrous tissue. Its nucleus looks like a cancer but the cells have not broken out of their capsule, and surgery to remove the entire thyroid followed by treatment with radioactive iodine is unnecessary and harmful, the panel said. They have now renamed the tumor. Instead of calling it “encapsulated follicular variant of papillary thyroid carcinoma,” they now call it “noninvasive follicular thyroid neoplasm with papillary-like nuclear features,” or NIFTP. The word “carcinoma” is gone.

Many cancer experts said the reclassification was long overdue. For years there have been calls to downgradesmall lesions in the breast, lung and prostate, among others, and to eliminate the term “cancer” from their name. But other than the renaming of an early stage urinary tract tumor in 1998, and early stage ovarian and cervical lesions more than two decades ago, no group other than the thyroid specialists has yet taken the plunge.

In fact, said Dr. Otis Brawley, chief medical officer at the American Cancer Society, the name changes that occurred went in the opposite direction, scientific evidence to the contrary. Premalignant tiny lumps in the breast became known as stage zero cancer. Small and early-stage prostate lesions were called cancerous tumors. Meanwhile, imaging with ultrasound, M.R.I.’s and C.T. scans find more and more of these tiny “cancers,”especially thyroid nodules.

“If it’s not a cancer, let’s not call it a cancer,” said Dr. John C. Morris, president-elect of the American Thyroid Association and a professor of medicine at the Mayo Clinic. Dr. Morris was not a member of the renaming panel.

Dr. Barnett S. Kramer, director of the division of cancer prevention at the National Cancer Institute, said, “There’s a growing concern that many of the terms we use don’t match our understanding of the biology of cancer.” Calling lesions cancer when they are not leads to unnecessary and harmful treatment, he said.

The article goes on to discuss the fact that, while some major medical centers are starting to treat encapsulated thyroid tumors less aggressively, this is still not the norm in the rest of the country. It is a consistent pattern that there is a lag of over a decade between changes in evidence and the clinical practice of medicine, which therefore makes medical practice far less “evidence-based” than is commonly claimed and/or assumed.

Clearly, the truth about cancer’s true nature, and the cancer industry’s misrepresentations, is beginning to come to light via the very institutions like JAMA and the major media who have been responsible, historically, for generating so many commonly held misconceptions on the topic.

National Cancer Institute Admits Cannabis Use Causes 45% Reduction in Bladder, Breast and Liver Cancer


The National Cancer Institute recently released its report on medical marijuana. The overview of their conclusion is, THC (the active ingredient in marijuana) caused a 45 percent reduction in bladder cancer, remission in breast and liver cancer and more.

Medical-Marijuana

They have determined that there is no lethal dose of marijuana. And addictive potential is considerably lower than any other medicine available.

Among their findings, they have found that cannabis is not associated with adverse pulmonary function and does not cause lung cancer or any aerodigestive tract cancers. Cannabis does not cause other types of cancer either.

They found cannabis has great anti-tumoral activity. Through their testing they have determined that cannabis is more effective than conventional antiemetics (drugs that ease nausea). And inhaled marijuana was more effective in chemo-induced nausea than any other currently available treatment.

(Editor’s note- this article is written by Wyoming News which serves an entire state. We talk of the bottom of alternatives to inhaling marijuana.. But yes, it’s true about inhaled marijuana. Granted, you can also take cannabis in other forms medically prescribed by your doctor which we describe below.

Some of their other findings are: Cannabis appetite increase at 75 percent compared to the most effective medicine that has a 49 percent increase; weight increase at 11 percent compared to the most effective current medicine that has a 3 percent increase.

In opiate resistant cancer pain, marijuana had significant pain intensity relief, substantial analgesic effects, antiemetic effects and appetite simulation.

They also proved THC to be more effective then codeine. Some 10 mg of THC was more effective then 60 mg of codeine. There was no increase of the THC dose needed in long-term pain management.

Inhaled THC was shown to be more effective in neuropathic pain than current medicine. It also showed improved sleep quality and sense of well being and less anxiety.

These are just some of the findings of the National Cancer Institute.

The federal government has made it so no state can be prosecuted for implementing a medical marijuana program. That is why the 23 states (and our nation’s capital) with medical marijuana programs are still around.

Editors Notes: This is a guest piece by one of the bigger online papers for the entire state of Wyoming. We just spent many days in Colorado learning that most medical marijuana patients who are prescribed cannabis by their medical doctors and have their red cards for medical dispensaries and pharmacies actually get tinctures (aka “CBD oil” or cannabis oil)  Depending on their illness – the ratio of CBD: THC varies. We’re doing a documentary which will be out soon. We don’t sell any products on the site (but do have links to some things on Amazon) but we may recommend some of the higher quality legal CBD oils out there that we have used ourselves.

– See more at: http://www.healthnutnews.com/national-cancer-institute-finally-admits-thc-causes-45-remission-in-bladder-breast-and-liver-cancer/#sthash.ilgD3ure.Y3xIxJxy.dpuf

Cancer Biology


Why Research on Cancer Biology Is Critical to Progress against the Disease

Research on the biology of cancer starts with the simplest of questions: What is—and isn’t—normal?

To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread, or metastasis, of cancer cells.

Knowledge gained from such studies deepens our understanding of cancer and produces insights that could lead to the development of new clinical interventions. For example, studies of cell signaling pathways in normal cells and cancer cells have contributed greatly to our knowledge about the disease, revealing molecular alterations that are shared among different types of cancer and pointing to possible strategies for treatment.

The last few decades of basic research in cancer biology have created a broad base of knowledge that has been critical to progress against the disease. In fact, many advances in the prevention, diagnosis, and treatment of cancer would not have occurred without the knowledge that has come from investigating basic questions about the biology of cancer.

Opportunities in Cancer Biology Research

Scientists today have a growing understanding of the biology of a vast array of cancers driven by various mutations and across many body sites. New data and research approaches have created opportunities for researchers to study in detail many aspects of cancer biology, including how the normal biological programs of cell proliferation and death are altered during cancer and how the immune system responds to tumors.

The discovery of tumor stem cells in a range of cancers has created opportunities for researchers to identify these rare cells in both solid tumors and hematologic cancers, as well as to investigate the role of these cells at different stages of disease.

The recognition that the cancer cell is in a symbiotic relationship with the tumor microenvironment has created opportunities to study the interactions of cancer cells within the tumor or the host microenvironment. Researchers are now studying the molecular mechanisms and signaling pathways of cancer cell development, proliferation, and metastasis.

Growing interest in the microbiome, the community of microorganisms and viruses that inhabit the human body, has led researchers to investigate the role of the human microbiome in the initiation and progression of tumors.

New genetic technologies developed over the past decade have helped researchers examine the functional effects of genetic alterations that underlie the development of cancer. These tools have also been used to study epigenetic changes associated with cancer, mechanisms of DNA damage and repair, and gene regulation in cancer cells.

The introduction of increasingly powerful structural biology approaches have allowed researchers to characterize the structures of mutant proteins involved in cancer, such as RAS, and other molecules in greater detail than had been possible previously.

There are also opportunities to explore cancer biology through systems biology approaches. Researchers use a variety of information and tools, such as mathematical modeling, to describe the complex interactions among components of a biological system and make predictions that help guide and further refine experimental science.

Challenges in Cancer Biology Research

Basic research in cancer biology is often viewed as “high risk,” in part because the clinical applications of a given research project might not be clear at the outset. However, knowledge gained from studying cancer cell biology not only improves our understanding of the disease but is essential for the development of clinical advances that benefit patients, as recent progress in the areas of immunotherapy and cancer vaccines illustrates.

Nonetheless, because of the uncertainty about the outcomes of basic research in cancer biology, this area of research receives relatively little funding from sources that are driven by profit. For this reason, federal funding for cancer biology research is critical.

Collaboration across disciplines is increasingly necessary to better understand key mechanisms in cancer. Therefore, some investigators may need to develop tools and strategies for sharing and communicating research results.

NCI’s Role in Cancer Biology Research

NCI supports and directs research on the biological differences between normal cells and cancer cells through a variety of programs and approaches. For example, the Division of Cancer Biology (DCB) supports extramural researchers who are using a variety of methods to study cancer biology.

In addition to many of the topics mentioned above, DCB supports research on:

  • the metabolism of cancer cells, the responses of cancer cells to stress, and mechanisms involved in control of the cell cycle
  • biological agents (such as viruses and bacteria), host factors (such as obesity, co-morbid conditions, and age), and behaviors (such as dietary intake) that may cause or contribute to the development of cancer
  • immune regulation of the development and spread of tumors and approaches to improve immune targeting and destruction of cancer cells
  • genomic instability and related molecular, cytogenetic, and chromosomal effects during induction and progression to malignancy
  • the role of the microenvironment created by inflammation and the inflammatory signaling molecules in the formation and progression of tumors
  • processes and molecular targets where there is potential for therapeutic or preventive intervention
  • the effects of hypoxia on tumor cell invasion and metastasis
  • the role of somatic stem cells in determining tumor progression and metastatic behavior, and control of the stem cell niche by tumor microenvironment

NCI-supported research programs in cancer biology include the:

  • Physical Sciences in Oncology Network
    The goal of this initiative is to promote and foster the convergence of physical science and cancer research. Small transdisciplinary teams of physical scientists (engineers, physicists, mathematicians, chemists, and computer scientists) and cancer researchers (cancer biologists, oncologists, and pathologists) collaborate on solving problems such as determining which cell is the cell of origin for brain and hematopoietic tumors and exploring the use of three-dimensional images of single cells as cancer signatures.
  • Tumor Microenvironment Network (TMEN)
    The centers in this network focus on expanding our understanding of the role of the tumor microenvironment in cancer initiation, progression, and metastases. The goal of this initiative is to better understand the composition of the stroma in normal tissues and to learn how the tumor and stroma interact in cancer.
  • Barrett’s Esophagus Translational Research Network (BETRNet)
    This multidisciplinary, multi-institutional collaboration was established to better understand Barrett esophagus and to prevent esophageal adenocarcinoma. BETRNet aims to better understand esophageal adenocarcinoma (EA) biology; examine research opportunities associated with its precursor lesion, Barrett Esophagus; improve EA risk stratification and prediction; and provide strategies for EA prevention. The overriding goal is to decrease the incidence, morbidity, and mortality of this cancer.
  • Alliance of Glycobiologists for Detection of Cancer
    This consortium of tumor glycomics laboratories and their research partners study the cancer-related dynamics of complex carbohydrates. This program, which NCI sponsors with the National Institute of General Medical Sciences and the National Heart, Lung and Blood Institute, aims to study the structure and function of glycans in relation to cancer.
  • Molecular and Cellular Characterization of Screen-Detected Lesions Initiative
    The goal of this program is to undertake a comprehensive molecular and cellular characterization of tumor tissue, cell, and microenvironment components to distinguish screen-detected early lesions from interval and symptom-detected cancers. Researchers use various technologies and approaches to determine both the cellular and molecular phenotypes of early lesions, with the goal of better predicting the fate of early lesions.

NCI’s Centers of Excellence bring together intramural researchers from NCI’s Center for Cancer Research and Division of Cancer Epidemiology and Genetics to develop new projects and initiatives in various areas of cancer biology, including:

  • Chromosome Biology
    The experts affiliated with this center study the mechanisms involved in chromosome function through diverse research that includes mapping the dynamic changes of the genome and transcriptome during the development of cancer and translational research for the early diagnosis of cancer.
  • Integrative Cancer Biology and Genomics
    This center’s goal is to use advanced analytic technologies to define homogenous clusters of patients, who can then be treated with appropriate therapies. The researchers in this center build upon the immense amount of basic research data available in an effort to shorten the time between discovery and patient benefit by bringing together expertise in five areas: biomarkers and molecular targets, genomic approaches, human genomics and genetics, cancer inflammation, and integrative/systems biology and bioinformatics.

Bisphosphonates Linked to Lower Endometrial Cancer Risk


A class of drugs that prevents bone loss may also help reduce women’s risk of developing endometrial cancer, according to a new study published online December 22 in Cancer.

Women who had a history of taking bisphosphonates were about half as likely as women who had not taken the drugs to develop endometrial cancer.

The study looked only at bisphosphonates that contain nitrogen, which have the strongest anticancer effects among the class of drugs, according to prior studies.

Sharon Hensley Alford, PhD, from the Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, and colleagues looked at data from 29,254 women aged 60 years and older in the National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The survey included a questionnaire on bone health and use of medications, including bisphosphonates.

Among the women who had used bisphosphonates, the researchers saw 8.7 cases of endometrial cancer per 10,000 person-years, compared with 17.7 cases per 10,000 person-years among women who had never used the drugs (rate ratio, 0.49; 95% confidence interval, 0.30 – 0.80).

After adjusting for a variety of variables, including age, race, smoking history, hormone therapy history, and body mass index, the hazard ratio for women taking the drugs compared with those not taking them was 0.56 (95% confidence interval, 0.34 – 0.93).
Endometrial cancer is the fourth most common cancer in women and the eighth most common cause of cancer death. Nearly half of all gynecologic cancers are endometrial. Endometrial cancer is most often diagnosed in women in their 60s and 70s, when they are postmenopausal and their bone density has decreased.

Previous research showed that bisphosphonates can slow tumor growth and the spread of cancer cells in patients with certain types of cancer, but no study had specifically looked at endometrial cancer.

The study’s main findings focused on the more common type 1 endometrial cancer, which is related to high estrogen levels. Researchers called for further studies with a larger sample to better assess the drug’s relationship to the more aggressive type 2 endometrial cancer, which is not hormonally related.