Drug Shortage Linked To Cancer Relapse

A drug shortage appears to have caused a higher rate of relapse among children, teens and young adults with Hodgkin lymphoma, researchers form St. Jude Children's Research Hospital reported this week. The scientists say this is the first example of the tragic consequences of the current drug shortage. They emphasized that protecting patient access to lifesaving treatment must always be the number one priority in any health care system.
Children, adolescents, and young adults with Hodgkin lymphoma in a national clinical trial showed an estimated two-year cancer-free survival rate that dropped from 88 to 75 percent due to a drug shortage.

The study began before any reported drug shortages, however, the change started in 2009 after a shortage of mechlorethamine became apparent. The drug mechlorethamine was replaced by cyclophosphamide for treatment of patients with middle or high risk Hodgkin lymphoma.

No study patients are deceased, but those who relapsed had more rigorous therapy that was linked with higher risks of infertility and other health issues later.

The results of comparing these two groups two years after their cancer diagnoses are published in the New England Journal of Medicine. The outcomes demonstrate the first available evidence of a drug shortage that resulted in disadvantages in specific patients.

History Of Drug Shortages

Recently, many caregivers and patients have had their medical treatments compromised by drug shortages, like mechlorethamine and other injectable drugs. Available since the 1960's for cancer treatment, mechlorethamine just became obtainable again.

Cyclophosphamide is a safe and effective substitute for mechlorethamine, used for decades for treatment of children and adults with Hodgkin's lymphoma.

Monika Metzger, M.D., an associate member of the St. Jude Department of Oncology and the study's principal investigator, said:

"This is a devastating example of how drug shortages affect patients and why these shortages must be prevented. Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available."

Previous shortages have most frequently been solved using substitutions. This study has given a real face to the drug shortage problem, showing that it is real. There are actual therapies that are unable to be given because drugs are just not available.

Michael Link, M.D., the senior author and professor of pediatrics in hematology-oncology at Stanford, as well as a member of the pediatric hematology-oncology service at Packard Children's Hospital, explains:

"Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed."

Results of Drug Substitutions

Hodgkin lymphoma is cancer that attacks the lymph system and makes up approximately six percent of childhood cancers. Around 90 percent of patients in the United States with this cancer will become long-term survivors.

In 2002, the five institutions collaborating on this study worked as the Pediatric Hodgkin Consortium and accepted a seven-drug chemotherapy treatment course, which included mechlorethamine, to treat high risk child patients. The researchers aimed to avoid infertility and other issues and maintain high cure rates.

In 2006, a companion study started for patients with intermediate-risk disease. The risk groups are defined by how far the cancer has spread, the location and number of lymph nodes involved, as well as the experience of negative symptoms like night sweats, fever, and weight loss.

Patients underwent 12 weeks of the seven-drug chemotherapy treatment course. They also received radiotherapy with their dose given in accordance to their chemotherapy response. Once mechlorethamine was no longer available, the substitution cyclophosphamide was allowed in its place.

Results for cancer patients are calculated in terms of cancer-free survival, also known as the number of years patients live disease-free. When investigators looked at the substitution's influence, they saw that approximate disease-free survival was 88 percent for the 181 patients whose treatment included mechlorethamine.

For the 40 patients who were given cyclophosphamide, the rate was 75 percent. The variation prompted researchers to stop enrolling new patients in the trials.

As a whole, patients who had the cyclophosphamide experienced less negative symptoms and were more inclined to have intermediate-risk, rather than high-risk Hodgkin lymphoma. The authors note that there is no valid explanation for the significant difference in event-free survival besides the drug substitution.

The patients in the study were between the ages of 3 and 21, with half being under 14 years. Relapsed patients underwent additional therapy. Extra treatment included extensive chemotherapy and a stem cell transplant using the patient's own blood-creating stem cells.

The investigators said it is too early to determine whether these patients will experience the same long-term survival rates as those who did not get their cancer back.

Aspirin Tied To Lower Risk For Liver Cancer And Death From Liver Disease

A new study from the US finds that use of aspirin is tied to a reduced risk for hepatocellular carcinoma, the most common type of primary liver cancer, and also to a reduced risk of death from chronic liver disease.
Vikrant V. Sahasrabuddhe, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and colleagues, write about their findings in the 28 November online issue of the Journal of the National Cancer Institute, JNCI.

Hepatocellular carcinoma occurs mainly in people with chronic liver disease. Some studies suggest the cancer could be a result of the chronic inflammation in liver disease affecting cellular processes.

NSAIDs as Cancer Preventers

Because of their anti-inflammatory properties, and their widespread use to prevent heart problems and cerebrovascular diseases like stroke, researchers are investigating the potential of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) as cancer preventers.

However, a recent study published in JNCI in August, suggests while the evidence is encouraging, the cancer-protective effect of NSAIDs is not as large as previously thought, and not enough to outweigh the risks (primarily of serious bleeding in the gut), and concludes it is too early to recommend people start taking them to ward off cancer.

What the Researchers Did

In the meantime, although more studies are looking at the potential anti-cancer effect of NSAIDs, the link to risk for liver cancer and death from chronic liver disease remains unclear, say the authors of this new JNCI paper, where they describe how they carried out an observational study of 300,504 men and women aged 50 to 71 years.

The participants, who were enrolled in the National Institutes of Health-AARP Diet and Health Study, had reported their use of aspirin and other NSAIDs and were followed for 10 to 12 years.

The researchers were able to link the NSAID use data from these participants to registered diagnoses of 250 cases of hepatocellular carcinoma and 428 cases of chronic liver disease.

What They Found

When they analyzed the links they found participants who used NSAIDs had a lower risk of hepatocellular carcinoma and a reduced risk of death from chronic liver disease compared to participants who did not use the drugs.

But when the researchers differentiated between aspirin and non-aspirin NSAIDs, there were some marked differences.

Participants who used aspirin showed a 41% reduced risk for hepatocellular carcinoma and a 45% reduced risk of death from chronic liver disease.

Whereas participants who used non-aspirin NSAIDs showed no reduced risk for for hepatocellular carcinoma, and a 26% reduced risk of death from chronic liver disease.

Sahasrabuddhe and colleagues write:

"Aspirin, in particular, when used exclusively or with other non-aspirin NSAIDs showed a consistent protective effect related to both HCC [hepatocellular carcinoma] incidence and CLD [chronic liver disease] mortality, regardless of the frequency or exclusivity of use."

If confirmed, these associations with the use of aspirin "might open new vistas for chemoprevention of HCC and CLD," they conclude.

Experts Say Fine to Look at NSAIDs, But Also Need to Improve Established Approaches

In an accompanying editorial, researchers from the Department of Epidemiology and Community Medicine at the University of Ottawa in Canada, note that the known causes of chronic liver disease and primary liver cancer are use of alcohol, and hepatitis B and C virus infections, and there have also been suggestions of a link with diabetes and obesity.

"We already have cheap, readily available interventions," they write, citing examples such as vaccines for hepatitis B and C virus, although "effective strategies for reduction of HBV and HCV are not always available or fully applied."

"Also, alcohol abuse and obesity are complex and multifactorial challenges that require interventions at the individual and system levels," they add, concluding that while we should continue to explore the potential for new drug strategies like NSAIDs, we should not lose sight of the need to improve established practices and interventions.

Coffee Drinking May Halve Risk Of Mouth And Throat Cancer

A new study from the US finds people who drink more than 4 cups of caffeinated coffee a day have half the risk of dying from oral/pharyngeal (mouth and throat) cancer as people who drink it either occasionally or not at all. However, the researchers say their findings need to be confirmed by more research, and for now should just be received as good news for coffee drinkers and not be used as a reason to recommend everyone should drink 4 cups of coffee a day.
Lead author Janet Hildebrand and colleagues from the American Cancer Society (ACS) in Atlanta, Georgia, write about their findings in a paper published online first on 9 December in the American Journal of Epidemiology.

Oral/Pharyngeal Cancer

Oral/pharyngeal or mouth and throat cancer is rarely diagnosed in the early stages because symptoms usually do not appear until the cancer is advanced. Also, the symptoms can be mistaken for something else, such as toothache.

The cancer can sometimes be spotted early during a routine exam by a doctor, dentist, or dental hygienist, and some dentists and doctors suggest you look at your mouth in a mirror at least once a month to check for symptoms.

The most common symptoms are a mouth sore that fails to heal, or a pain in the mouth that doesn't go away.

The biggest risks for developing oral/pharyngeal cancer are tobacco and alcohol use. Most people who have it are tobacco users.

Infection with the human papillomavirus (HPV) is also a risk factor, especially in people who do not use tobacco. The number of cases of oral/pharyngeal cancer tied to HPV has risen sharply in the last thirty years.

Researchers Examine Link with Coffee

Previous epidemiological studies have suggested coffee drinking is linked to a reduced risk for mouth and throat cancer.

It has also been suggested that it may not be the caffeine in coffee, but the fact it is rich in antioxidants, polyphenols, and other compounds, that help prevent or slow the development of cancer.

For their study, Hildebrand and colleagues used data from the Cancer Prevention Study II, a prospective US cohort study that the ACS started in 1982.

That study gathered a wealth of lifestyle and health information on 968,432 men and women, including their tea and coffee consumption. When they enrolled on the study, none of the participants had cancer, but over the 26 years of follow up, 868 died from oral/pharyngeal cancer.

When they analyzed the tea and coffee consumption in relation to deaths from oral/pharyngeal cancer, the researchers found those participants who reported drinking more than 4 cups of caffeinated coffee a day had a 49% lower risk of death from oral/pharyngeal cancer compared to those who reported not drinking coffee at all or only an occasional cup.

The link was not affected by gender, tobacco and alcohol use.

The researchers found an insignificant link with decaffeinated coffee, and none at all with tea.

Conclusion and Next Step

The researchers conclude:

"In this large prospective study, caffeinated coffee intake was inversely associated with oral/pharyngeal cancer mortality. Research is needed to elucidate biologic mechanisms whereby coffee might help to protect against these often fatal cancers."

Hildebrand says in a press statement:

"We are not recommending people all drink 4 cups of coffee a day. This is just a little bit of good news for those of us who enjoy coffee."

"There may be some other effects of coffee that may prevent people with certain conditions from drinking a lot of caffeine," she cautions, noting that:

"This study is about just one cancer site among many. There needs to be much more consistent research before we can support the conclusion that coffee should be consumed for cancer prevention."

The team is now planning to analyze links between coffee consumption and cancer in a more diverse population in the ACS's new Cancer Prevention Study - 3 (CPS-3).

The Society hopes to recruit at least 300,000 adults from a range of ethnic and racial backgrounds across the US to take part in CPS-3, which aims to increase knowledge of how to prevent cancer.

There has been a lot of debate recently about the benefits and harms of coffee drinking, with more recent news suggesting the benefits probably outweigh the harms.

But researchers spreading the good news are all saying the same thing, as Hildebrand and colleagues themselves point out in this latest study: while there appear to be some health perks from drinking coffee, there are also a few cautions, and the evidence is not solid enough to actively encourage people to go out and drink coffee.

One In Two Men Will Develop Cancer

New figures for the UK predict a man's risk of developing cancer during his lifetime will rise to one in two by 2027, largely because more people are living longer.
The figures, released by Cancer Research UK on Wednesday, show that in the next 15 years, 50 men out of every 100 in the UK will be diagnosed with cancer at some point during their lives, compared with 44 out of 100 in 2010.

They also show the risk for women developing cancer will rise from 40 to 44 out of every 100 over the same period.

The backdrop to these new figures is age: the biggest risk factor for cancer. Living longer means a higher risk of developing cancer. And in the UK, as in other developed nations, more people are reaching an age where they are more likely to develop cancer.

Harpal Kumar, chief executive of Cancer Research UK, says in a statement that their figures are a "glimpse into the future".

"On the plus side our life expectancy is increasing but this also means more of us are likely to be diagnosed with cancer," he says.

But there is also another backdrop: thanks to research, cancer diagnosis and treatment is improving all the time, so while the risk of developing cancer is going up, so is the chance of surviving it.

Experts say prostate cancer, bowel cancer and melanoma are among those most likely to rise in the next 15 years.

Prostate Cancer

Prostate cancer remains a huge challenge: cases are growing and there is no reliable way to identify the ones that are life-threatening.

"Prostate cancer needs research," says Professor Malcolm Mason, prostate cancer expert at Cancer Research UK.

Mason says there are many questions that research still needs to answer. As the population ages, more and more men will be diagnosed with prostate cancer.

"Over the last 40 years prostate cancer incidence rates in Great Britain have tripled, and three-quarters of cases are diagnosed in men aged over 65 years," says Mason.

However, there are some glimmers of hope, such as a paper published recently in Molecular Cancer Research where scientists at the Mayo Clinic in Florida report finding an enzyme called PRSS3, or mesotrypsin, that may help drive aggressive prostate cancer. They believe the discovery could lead to a test and better treatment.

Another promising area of research is that being carried out by Cancer Research UK scientists. They are studying a protein called microseminoprotein-beta (MSMB) that may help identify men at greater risk for prostate cancer. They suggest this could be a more accurate marker than the one currently used in screening tests, the prostate specific antigen (PSA).

 

For instance, in a paper published in 2010 in the journal PLoS ONE, Cancer Research UK scientists conclude that "urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades."

Mason says it's men at higher risk for prostate cancer who are likely to benefit most from screening, and it might be better to target those men that to try and screen all men.

However, it is "only through continued research that we'll be able to offer improved tests to reduce the number of men who die from the disease," he adds.

Bowel Cancer

Research into bowel cancer has already improved diagnosis and prevention. Researchers have shown how a one-off flexi-scope (single flexible sigmoidoscopy) test could reduce new cases and deaths from bowel cancer in those who take it up.

For example, one study published in 2011 in the Journal of the National Cancer Institute, shows how a single flexible sigmoidoscopy screening reduced bowel cancer incidence and deaths.

In that study, disease incidence was lowered by 18% and deaths by 22%. Among screened patients, incidence was reduced by 31%, and by 46% for advanced cases. And deaths in screened participants were reduced by 38% compared to controls.

Cancer Research UK also ran a 16-year trial that showed deaths from bowel cancer fell by 43% and cases by a third, in participants who had just one flexi-scope test.

"Our research showed for the first time that we could dramatically reduce the incidence of bowel cancer, and the number of people dying from the disease, by using this one-off test," says Professor Wendy Atkin, Cancer Research UK's bowel cancer screening expert who led the research.

Atkin describes their work as a "fantastic example" of the benefits research brings; "there is no other way we would be able to develop new treatments, know whether a new treatment is better or worse and know who should receive it," she adds.

Melanoma

Researchers by Cancer Research UK and others around the world has led to promising new treatments for advance melanoma, bringing hope to patients.

However, it is also essential that efforts to prevent the disease continue.

Most cases of melanoma are due to over-exposure to the sun's UV rays, and sunbeds. One study published recently shows how sun damage causes newly discovered melanoma-driving genetic changes.

Other areas where research is making inroads, is finding out how melanoma cells circumvent the immune system, and also fighting the cancer's resistance to chemotherapy.

Public Generosity

"It's only through research that we will be able to beat cancer. We need to do more work to understand what drives cancer and how we can prevent it, as well as developing new treatments to reduce the number of people who will die from it," urges Kumar.

"Understanding the biology of cancer is rather like completing a complex jigsaw puzzle. Many pieces have already fallen into place but we need more research before we can complete the picture. And thanks to the generosity of the public, our world class scientists are playing a leading role in beating this devastating disease," he adds.

Cancer Research UK has released the figures ahead of a UK television advertising campaign that launches on Boxing Day whose message is cancer will only be defeated through research.

UK charities are facing tough times. A recent report compiled by the Charities Aid Foundation and the National Council for Voluntary Organisations finds that charity giving in the UK fell by 20% in real terms in 2011-2012.

Extended Use Of Zytiga Approved By FDA For Late-Stage Prostate Cancer

Today the U.S. Food and Drug Administration (FDA) lengthened the approved use of Zytiga (abiraterone acetate) as treatment for men with late-stage, castration-resistant prostate cancer (metastatic) before undergoing chemotherapy.
First approved in 2011, Zytiga is used in patients whose prostate cancer developed further after treatment with docetaxel, a chemotherapy drug. Zytiga is a pill that reduces the production of testosterone, the male sex hormone.

This drug is known to preserve quality of life, reduce the spread of cancer, as well as slow the development of pain and the decline of an individual's overall health, according to a study released earlier this year.

A separate study also recommended Zytiga in combination with prednisone for late-stage, castration-resistant prostate cancer, and showed that Zytiga is being used successfully in over 40 different countries.

Tumor growth during prostate cancer is triggered by testosterone. Surgery or drugs are used to decrease the effects or block creation of testosterone.

Castration-resistant prostate cancer is when the prostate cancer cells keep growing even without large amounts of testosterone.

Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, says,

"Today's approval demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment."

The FDA examined the application for this altered use of Zytiga under the agency's priority review program. This specific program gives an accelerated six-month examination for drugs that may give major benefits in treatment or offer a treatment when no current therapy exists.

A clinical study was conducted using 1,088 men with late-stage, castration-resistant prostate cancer who had not yet undergone chemotherapy which established the successfulness and safety of Zytiga.

The study was developed to calculate the length of time a patient existed before death as well as the amount of time a patient lived without further tumor development. These two time periods were measured by imaging known as radiographic progression-free survival, or rPFS.

Patients who took Zytiga had a medical survival rate of 35.3 months, while those taking a placebo had a 30.1 month survival rate. Results showed that Zytiga enhanced rPFS. The median rPFS was 8.3 months in the placebo group, while in the other group had not been achieved yet at the time of calculation.

Side effects that were seen included:

• joint swelling or discomfort
• hot flush
• diarrhea
• vomiting
• fatigue
• swelling caused by fluid retention
• cough
• urinary tract infection
• bruising
• shortness of breath
• high blood pressure

The most frequently documented laboratory abnormalities were:

• high levels of the enzyme alkaline phosphatase
  -this could be a sign of other medical problems
• low levels of potassium, lymphocytes, and phosphorous in the blood
• high levels of fatty acids, liver enzymes, and sugar in the blood

Written by Kelly Fitzgerald

View drug information on Zytiga.

Trojan Horse" Cancer Treatment Eliminates Cancer In Mice

An experimental treatment that uses white blood cells like "Trojan horses" to carry a tumor-busting virus, completely abolished prostate cancer spread after chemo or radiotherapy in mice. The researchers hope clinical trials in human patients with prostate cancer can start in early 2013.
Claire Lewis, a professor at the Department of Oncology in the University of Sheffield, and colleagues, write about their findings in a recent issue of the journal Cancer Research.

Using immune cells to carry viruses to treat cancer is an emerging field. In June 2012, researchers reported discovering how when a cancer-killing virus is injected in the bloodstream it hitches a ride on blood cells and evades attack from the immune system, allowing it to reach cancer tumors, and start destroying cancer cells.

Lewis and her team have also been investigating this approach, and discovered that the challenge is to get enough of the virus deep into the tumor.

After chemotherapy or radiotherapy, the immune system floods the tumor with white blood cells called "macrophages" that mop up the debris caused by the therapy.

UK researchers have suggested that a "Trojan Horse" cancer therapy has completely eliminated the spread of prostate cancer in mice.

Lewis and colleagues found that injecting macrophages carrying a tumor-busting or "oncolytic virus" (OV) into the bloodstream at the exact moment when this surge occurs, they "surf the wave" of white blood cells and inundate the tumor in large numbers.

"... we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the post-treatment regrowth of primary prostate tumors in mice, and their spread to the lungs for up to 27 or 40 days respectively," they write.

The treatment also "significantly increased the lifespan of tumor-bearing mice compared to those given docetaxel or irradiation alone," they add.

In a statement released last week, Lewis says:

"Our "Trojan horse" can convert a patient's own white blood cells into tiny tumor-killing machines which fight to prevent tumor regrowth after the end of chemo or radio therapy treatment."

"This is very empowering for patients who have been undergoing rounds and rounds of chemotherapy or radiotherapy because treatment means it is their own white blood cells doing the work and blasting the cancer," she explains.

First author Munitta Muthana, from Sheffield's Department of Infection and Immunity, adds:

"With the initial support of the Yorkshire Cancer Research (YCR) and latterly Prostate Cancer UK, our new therapy has been developed to treat prostate cancer; however, it has the potential to be used to treat patients with any form of cancer."

Kate Holmes, Head of Research at Prostate Cancer UK describes the study as an "exciting development" in the "Trojan Horse" approach.

"It demonstrates that this innovative method of delivering a tumor-killing virus direct to the cancer site is successful at reducing the development of advanced prostate tumors in mice which have been treated with chemotherapy and radiotherapy."

"If this treatment goes on to be successful in human trials, it could mark substantial progress in finding better treatments for men with prostate cancer which has spread to the bone, and ensuring the impact of more traditional therapies is maximised," she adds.

Meanwhile, across the Atlantic in the US, researchers at the Mayo Clinic have discovered th an  enzyme called PRSS3, or mesotrypsin, may help drive aggressive prostate cancer. They suggest their finding will lead not only to more effective treatment of advanced prostate cancer, but may also help identify those at high risk for the aggressive form.

Prostate cancer is the most common cancer in men in the UK, where rates have tripled in the last 40 years.

In 2009, about 40,800 men in the UK were diagnosed with the disease, or around 112 a day.