Wyeths Menopause Hormones Risk Of Lung Cancer Demises
After five years on Wyeths Prempro, a combination of the hormones estrogen and progestin, 67 women died from non-small cell lung cancer, compared with 39 on placebo, the research showed. Results of the trial, which examined women age 50 to 79 and included current and former smokers, were presented today at the American Society of Clinical Oncology meeting in Orlando.
Sales of the pills plunged in 2002 after a U.S. study linked the therapy to breast cancer and cardiovascular risks. As many as 6 million women took the menopause treatments before the study curbed use. The products generated $1.1 billion last year, down from more than $2 billion in 2001.
“This is a new finding that tells us women who smoke shouldnt take estrogen and progestin for menopause symptoms,” said Rowan Chlebowski, the study author and a researcher at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, in an interview.
Tobacco use causes almost 80 percent of lung cancer deaths in women, according to the Atlanta-based U.S. Centers for Disease Control and Prevention. More lung cancer cases were also diagnosed in women on hormones, though the difference wasnt statistically significant, todays study found.
See the Logic
“I can see the logic of that kind of recommendation,” for women smokers to avoid hormone pills, said Joseph Camardo, head of medical affairs at Madison, New Jersey-based Wyeth, in an interview. “I would absolutely advise women not to smoke.” Camardo said he had not seen the data.
About 200,000 Americans are diagnosed with lung cancer each year, and 160,000 die from it, more than any other tumor, according to the CDC.
About 85 to 90 percent of lung malignancies are of a variety called non-small cell, the type in todays study, according to the American Cancer Society, an advocacy group.
The trial analyzed lung cancer diagnosis and death among 16,608 patients who participated in the Womens Health Initiative, the same U.S. research project that identified other risks of hormone therapy seven years ago.
Among current and former smokers studied in the research, there were 56 deaths for women treated with hormones and 34 deaths with placebo. Among non-smokers, there were 9 deaths for women on hormones and 5 deaths for patients taking a placebo.
Menopause Symptoms
Patients today take lower doses of Wyeths hormones to reduce their risk of breast cancer and heart attacks. Prempro combines two hormones, estrogen and progestin, to curb the risk of uterine cancer that is linked to taking estrogen alone. Premarin, an estrogen-only pill, is given to women who have had hysterectomies, surgery removing the uterus.
Prescribing information on the label for Wyeths hormones details risks identified by earlier research from the WHI study, including breast cancer and heart attacks. No warnings about lung cancer are currently included.
More than 5,000 lawsuits have been filed against Wyeth, alleging its hormones caused cancer.
New York-based Pfizer Inc., the worlds largest drugmaker, said in January it would buy Wyeth for about $65 billion.
Lillys Alimta May Help Lung Cancer Patients Live Months Longer
Patients either took Alimta or a placebo every 21 days after their disease had been controlled with a standard therapy. People taking the drug lived 3 months longer overall than those on placebo, according to the Indianapolis-based companys research being presented today at the American Society of Clinical Oncology meeting in Orlando, Florida.
More patients die from lung cancer than from any other form of the disease, according to the U.S. Centers for Disease Control and Prevention. The data have been submitted to U.S. regulators and are under review for approval of the new use for Alimta, said Richard Gaynor, Lillys head of oncology. Alimta, which generated $1.15 billion in 2008 revenue, is approved in the U.S. as a first-choice therapy and as a second-line treatment after initial therapy fails.
“We think the concept of maintenance therapy is very exciting, the notion that some kinds of cancer may be a chronic disease,” said John Lechleiter, the chief executive officer of Lilly, in a telephone interview. “Its exciting to think that there are some kinds of cancer where, while it isnt eradicated, it might be contained.”
The drugs use as maintenance therapy got the backing yesterday of a European Medicines Agency panel, Lilly said in a statement.
Living Longer
Overall, the study found patients who were not on a maintenance therapy lived 10.6 months, and Alimta patients survived 13.4 months. Those patients on placebo went 2.6 months without their cancer worsening, while people talking Alimta had 4.3 months before their cancer worsened.
“In lung cancer, these results are very dramatic,” said Richard Gaynor, Lillys head of oncology. “This is the first example where maintenance therapy worked really impressively. Its a paradigm-changing study.”
The study also found that a subset of patients with types of cancer that originated in certain large cells in the lungs lived 5 months longer on Alimta than the comparison group. Patients who had so-called nonsquamous cell cancer survived 15.5 months, and went 4 months without worsening on the Lilly drug. Comparable placebo patients survived 10 months, and went 1.8 months without worsening.
Targeting Therapies
“We can create tremendous value by targeting therapies,” Lechleiter said. “That way the payer doesnt waste their money and the patient and doctor dont waste their time.”
Seamus Fernandez, an analyst for Leerink Swann, said Alimta has the potential to generate $1.5 billion in sales this year, and increase to $2.9 billion in 2015.
About 85 to 90 percent of lung cancers are nonsmall cell, according to the American Cancer Society, an advocacy group. Between a quarter and a third of all lung cancers are squamous cell carcinomas, which begin in cells in the lungs that look like fish scales. Patients who had nonsmall cell lung cancers that didnt start in the squamous cells did best on Alimta maintenance therapy.
Researchers said the most common side effects were fatigue and a disorder of the white blood cells. Other side effects, each found in less than 1 percent of patients, were nausea, vomiting and infection.
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Antidepressants Axe Effectiveness Of Tamoxifen In Breast Cancer
Tumors were more than twice as likely to return after two years in women taking the antidepressants while on the cancer drug, compared with those taking tamoxifen alone, the study showed. The research, by Medco Health Solutions Inc., was presented today at a meeting of the American Society of Clinical Oncology in Orlando.
Doctors began treating hot flashes with antidepressants, an unapproved use, after a U.S. study seven years ago linked the former standard remedy, hormone replacement therapy, to an increased risk of breast cancer and heart attacks. Other types of antidepressants, such as Wyeths Effexor, may be safer for women on tamoxifen than Paxil or Prozac, said Powel Brown, director of cancer prevention at the Lester and Sue Smith Breast Cancer Center at Baylor College of Medicine in Houston.
“Effexor doesnt interfere with tamoxifen so that is the preferred drug for oncologists to treat hot flashes,” said Brown, who wasnt involved in the study. “We need to get that message out to primary care doctors and psychiatrists and gynecologists so they will be aware that antidepressants like Paxil have a risk of inhibiting tamoxifen.”
Hot flashes are a side effect of tamoxifen.
Breast cancer is the second most common malignancy in women, after skin tumors, according to the Atlanta-based U.S. Centers for Disease Control and Prevention. About 187,000 women were diagnosed with breast cancer and 41,000 women died from it in 2005, the most recent year for which CDC data are available.
Tumor Fighter Enzyme
Tamoxifen cant combat tumors until it mixes inside the body with a liver enzyme called CYP2D6 to morph into an active tumor fighter called endoxifen. Many antidepressants use the same enzyme, sapping supplies needed for tamoxifen to do its work.
“The patient might as well be taking a placebo,” said Frankie Ann Holmes, associate director of breast cancer studies at U.S. Oncology Research in Houston, in a 2005 report published by ASCO. Holmes said antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, shouldnt be used in patients taking tamoxifen.
SSRIs include Paxil and Prozac, and Zoloft, as well as Forest Laboratories Inc.s Celexa and Lexapro. Paxil is the strongest in blocking availability of the CYP2D6 enzyme, Holmes found.
In the study presented today, Medco searched medical and pharmacy records of 10.7 million people to see what happened to women taking tamoxifen along with antidepressants known to interfere with the CYP2D6 enzyme.
Twice the Risk
The study included 945 women on tamoxifen, and an additional 353 also using an antidepressant.
“This is the first large outcomes-based study to reinforce earlier research questioning the use of Paxil and Prozac in patients taking tamoxifen,” said Robert Epstein, a study author and chief medical officer for Medco, a pharmacy benefits company based in Franklin Lakes, New Jersey.
Medco Warning
Medco warns pharmacists to check with doctors before filling prescriptions for SSRIs if women are also taking tamoxifen, Epstein said. “We would encourage doctors to consider an alternative if there is an option that would also address hot flashes or depression without interfering with tamoxifen,” he said.
Outside science advisers to the U.S. Food and Drug Administration in Oct. 2006 reviewed the potential for certain antidepressants to render tamoxifen ineffective.
The committee of scientists concluded that information on this drug interaction should be added to tamoxifens label. The current label doesnt have any statements about this risk.
FDA spokeswoman Rita Chappelle didnt immediately respond to a telephone message seeking comment.
Astrazeneca Cancer Pill Works With Chemo to Slow Tumors
Adding Zactima to treatment with chemotherapy shrank tumors and reduced disease symptoms, the research found. It also lengthened the time before the cancer progressed to 17.3 weeks, compared with 14 weeks for those on chemotherapy only. Patients taking Zactima didnt live significantly longer.
The finding was reported today at the American Society of Clinical Oncology in Orlando. It makes Zactima the first pill to work with chemotherapy for advanced lung cancer patients who havent been helped by initial treatments, researchers said. AstraZeneca will apply for U.S. approval by the end of the month, the London-based drugmaker said. The drug may generate annual sales of $500 million a year by 2014, according to an April report by Bank of America Merrill Lynch in New York.
“For the first time, we are actually improving efficacy” for patients on chemotherapy, said Peter Langmuir, medical science director at AstraZeneca, in an interview before the conference. “For patients in second-line treatment, there are three agents approved; none of them has been shown to be any better than docetaxel,” a form of chemotherapy.
The trial, called Zodiac, tested the drug in 1,391 patients.
160,000 Deaths
If approved, Zactima would compete with Roches Tarceva and Eli Lilly & Co.s Alimta for patients in secondary treatment. Another study presented at ASCO found that Zactima was no better or worse than Tarceva when used alone. Zactimas advantage would be as a proven combination therapy, Langmuir said.
About 200,000 Americans are diagnosed with lung cancer each year and 160,000 die from it, according to the U.S. Centers for Disease Control and Prevention. While initial treatment with chemotherapy and radiation can slow the disease, about half of patients eventually qualify for a second line of treatment, Langmuir said.
Zactima attacks tumor cells in two ways, combining properties found in Avastin and Tarceva. Like Avastin, it blocks the vascular endothelial growth factor, which creates the blood vessels needed to feed a tumor. Like Tarceva, it attacks cancer cells by interfering with epidermal growth factor receptor, a protein needed to grow and divide.
Immediate Clinical Use
“This study will have immediate clinical implications,” said Roy Herbst, lead author of the study and chief of thoracic medical oncology at the University of Texas MD Anderson Cancer Center in Houston. He said more research should be done to determine which patients are most likely to respond to the combined treatment.
Zactima failed to reach its goals in two earlier studies. One report hoped to show that Zactima was better than Tarceva when given as a solo treatment in research involving 1,240 patients. The other study, in 534 people, examined whether giving Zactima in addition to Alimta would help prevent cancer from progressing more than Alimta alone.
The most common side effects with adding Zactima to chemotherapy were rash, diarrhea and hypertension. However, patients experienced less nausea, vomiting, and anemia than with docetaxel alone.
Docetaxel is sold as Taxotere by the French drugmaker Sanofi-Aventis.
Scientists Identify New Lethal Virus In Africa
Its not clear how the first person became infected, but the bug comes from a family of viruses found in rodents, said Dr. Ian Lipkin, a Columbia University epidemiologist involved in the discovery.
“This one is really, really aggressive” he said of the virus.
A paper on the virus by Lipkin and his collaborators was published online Thursday on in PLoS Pathogens.
The outbreak started in September, when a female travel agent who lives on the outskirts of Lusaka, Zambia, became ill with a fever-like illness that quickly grew much worse.
She was airlifted to Johannesburg, South Africa, where she died.
A paramedic in Lusaka who treated her also became sick, was transported to Johannesburg and died. The three others infected were health care workers in Johannesburg.
Investigators believe the virus spread from person to person through contact with infected body fluids.
“Its not a kind of virus like the flu that can spread widely,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund the research.
The name given to the virus – “Lujo” – stems from Lusaka and Johannesburg, the cities where it was first identified.
Investigators in Africa thought the illness might be Ebola, because some of the patients had bleeding in the gums and around needle injection sites, said Stuart Nichol, chief of the molecular biology lab in the CDCs Special Pathogens Branch. Other symptoms include include fever, shock, coma and organ failure.
Genetic extracts of blood and liver from the victims were tested at Columbia University in New York, and additional testing was done at CDC in Atlanta. Tests determined it belonged to the arenavirus family, and that it is distantly related to Lassa fever, another disease found in Africa.
The drug ribavirin, which is given to Lassa victims, was given to the fifth Lujo virus patient – a Johannesburg nurse. Its not clear if the medicine made a difference or if she just had a milder case of the disease, but she fully recovered, Nichol said.
Along with Faucis institute, the National Heart, Lung, and Blood Institute and Google also helped fund the research.
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Diabetes Cases In Children to Double By 2020, Researchers Say
The number children under 15 with Type 1 diabetes will rise to about 160,000 across Europe in 2020 from 94,000 in 2005, according to a study in the U.K. journal The Lancet. Lead researcher Chris Patterson from the Queens University in Belfast expects the cases in children younger than 5 to double.
The gain is so rapid that it cant be explained by genetic links alone, the researchers said. Changes in lifestyle seen in nations with rising wealth, such as more births by caesarian section, greater height and weight, and fewer infections early in life, may be spurring the increase, they said. More cases will be diagnosed at younger ages than before and more children will have complications requiring hospital admission, they said.
“In the absence of any effective means to prevent Type 1 diabetes, European countries need to ensure appropriate planning of services and that resources are in place to provide high- quality care for the increased numbers of children who will be diagnosed with diabetes in future years,” Patterson wrote.
Type 1 diabetes is caused by insulin deficiency and must be treated with injections of the hormone, which regulates sugar levels in the blood. Type 2 diabetes, which often starts in adulthood, occurs as a result of reduced sensitivity to insulin as well as some insulin deficiency. Type 1 diabetes cases represent 10 percent of total diabetes cases. Children in Western countries are more often affected by Type 1 diabetes.
29,311 Cases
The study authors from the U.K., Hungary, Sweden and Denmark analyzed data from 20 centers in 17 European countries, which had registered a total of 29,311 cases of the illness between 1989 and 2003. They documented trends during that period to predict future trends in the disease in European children.
The researchers forecast about 24,400 new cases of Type 1 diabetes by 2020, with infants to 4-year-olds accounting for 29 percent, ages 5 to 9 for 37 percent, and 10- to 14-year-olds accounting for 41 percent. Countries in eastern and central Europe will have the most rapid increases.
A common complication of Type 1 diabetes is ketoacidosis, where the liver breaks down fats and proteins to provide energy in an unregulated fashion, leading to increased levels of acids in the blood, a condition which may be life-threatening. Ketoacidosis is one complication requiring hospitalization.
“It is imperative that efforts directed at surveillance of diabetes in young people continue and expand,” said Dana Dabelea from the University of Colorado in Denver in a comment accompanying the study.
Fda Is Reviewing Ranbaxys Corrective Strategy On Drugs to The U.s.
“The FDA is working very closely with the firm to ensure that all the Ranbaxy products currently in the U.S. market are safe and effective,” FDA spokesman Christopher Kelly said in an e-mail yesterday. “The next steps will be dependent on the actions identified” in the plan, he said.
U.S. sales of Ranbaxy, Indias biggest drugmaker, fell for two straight quarters after the U.S. Food & Drug Administration on Sept. 16 blocked the import of 30 medicines produced at two of its factories. The FDA decision to block the products in the U.S., the worlds largest drug market, led Ranbaxys stock to plunge 45 percent until Chief Executive Officer Atul Sobti said earlier this week that the company had submitted the plan.
The regulator in February barred Ranbaxy from introducing new generic medicines from one of the two plants. The FDA said Ranbaxy falsified data from the factory in Paonta Sahib, northern India. Drugs from that plant were approved for sale in the U.K. and Australia after a joint audit by regulators, Ranbaxy said March 23.
Ranbaxy, controlled by Tokyo-based Daiichi Sankyo Co., rose 0.4 percent to 262.85 rupees as of 10:31 a.m. in Mumbai trading, while Indias benchmark Sensitive Index gained 1 percent.
Sobti, who replaced Malvinder Singh as CEO under a plan by its parent to turn around the unprofitable company, said Ranbaxy expects the full approval process by the FDA to take months.
The FDA said it received Ranbaxys corrective action plan on May 18.
Study: Heat Effective In Treating Throat Condition
In a study of 127 people suffering from a heartburn-related problem known as Barretts esophagus, only about 1 percent who had a procedure that uses heat to burn off precancerous spots went on to develop cancer over the next year. Thats compared with more than 9 percent of those who got a fake treatment in which no cells were destroyed.
Barretts esophagus occurs when stomach acid backs up into the throat, causing the normal lining to be replaced by abnormal growth. Barretts sufferers are 30 times more likely than others to develop esophageal cancer, one of the deadliest forms of the disease.
Scientists do not know what causes esophageal cancer, but some suspect smoking, drinking and obesity may play a role. The American Cancer Society estimates 16,470 people will be diagnosed with the disease this year, and incidence has been rising.
Doctors typically perform down-the-throat exams and surgically remove the esophagus in severe cases of Barretts. A less drastic alternative, which has been available since 2005, uses a device down the throat and radiofrequency energy to destroy precancerous cells.
In the study published in Thursdays New England Journal of Medicine, Barretts patients who had signs of precancerous cells were treated with the device or given a sham procedure that did not involve heat.
After a year, 77 percent who had the procedure were free of precancerous spots compared with 2 percent who got the fake treatment.
More Barretts patients who underwent the heat procedure had pain for about a week afterward. One in the heat group suffered gastrointestinal bleeding and five developed narrowing of the esophagus.
Still, the study had a low complication rate, Dr. Jacques Bergman of the Academic Medical Center in Amsterdam wrote in an accompanying editorial.
The study was led by Dr. Nicholas Shaheen of the University of North Carolina at Chapel Hill. Several researchers and Bergman have received grants from or have other financial ties to Sunnyvale, Calif.-based Barrx Medical Inc., which makes the device and paid for the research.
The procedure, which takes about 30 minutes and is done in outpatient offices, costs about $2,000. It is covered by Medicare and most insurance plans.
However, its not for everybody with Barretts: Not all have precancerous cells and Bergman said it is too early to recommend it to Barretts sufferers who show no signs of abnormal spots.
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New England Journal: http://www.nejm.org
Mixed-race Patients Struggle to Discover Marrow Donors
But because the 28-year-old bodybuilder is one-quarter Japanese, his doctor warned him the outlook was grim. Glasgows background would make it almost impossible to find a match, which usually comes from a patients own ethnic group.
The doctor “didnt say it was slim-to-none. He didnt say it would be hard. He said zero chance,” Glasgows mother, Carole Wiegand, recalled with tears in her eyes. “When Nick heard that, it sent him plummeting.”
At a time when the number of multiracial Americans is rising, only a tiny fraction of donors on the national bone-marrow registry are of mixed race. The National Marrow Donor Program is trying to change that by seeking more diverse donors for patients suffering from leukemia, lymphoma and other blood diseases.
“The truth is, when people of different backgrounds marry and produce offspring, it creates more types that are harder to match,” said Michelle Setterholm, the programs director of scientific services. “The probability just gets lower when you have people of mixed ancestral DNA.”
The number of people who identify themselves as multiracial in the United States has grown from 3.9 million in 2000, the first year the census included the category, to 5.2 million in 2008. Mixed-race people account for 1.6 percent of the U.S. population.
The donor program has been pushing for years to recruit more racial minorities and mixed-race donors. So far, multiracial volunteers make up just 3 percent of the 7 million people on the registry.
That is higher than the percentage of mixed-race people in the U.S. But there are so many possible racial and ethnic combinations that finding a match can still be extremely difficult.
The reason that mixed-heritage patients are so hard to match can be found in the immune system.
Populations in different parts of the world developed certain proteins, or markers, that are part of the bodys natural defenses. These markers help the immune system determine which cells are foreign and should be rejected.
A match between two people who share many markers will reduce the risk of the donor and recipient cells attacking each other. Because certain markers tend to cluster in particular ethnic groups, matches are most often found among people of shared backgrounds. Multiracial patients often have uncommon profiles and a much harder time finding a donor.
About 6,000 patients in the U.S. are awaiting a bone marrow match.
Finding compatible organs for transplant is simpler. Organ matches rely essentially on blood type, which is not related to race.
From his Japanese grandmother, Glasgow got the almond shape of his eyes and cell markers that set him apart from most other whites. From his white grandparents, he got markers that set him apart from other Japanese.
Geary Moyas background – part Navajo, part Mexican – has kept his life on hold since 2005, when he was diagnosed with non-Hodgkins lymphoma. Chemotherapy has put his cancer in remission, but a bone marrow transplant is his only hope for a cure.
“I cant work. I cant plan. I just dont know what tomorrow will hold for me,” said Moya, a 51-year-old former manager of an appliance company.
He often visits bone marrow drives, where he tries to encourage prospective donors to sign up.
“If its not for me, itll help someone,” he said last week as he stopped by a booth registering potential bone marrow donors at California State University in Hayward. “Theres a whole list of people out there waiting for someone to come along.”
Who May Alter Pandemic Alert System After U.k. Cites Confusion
The agency will ask a group of scientists and public health officials for advice on how to improve the decade-oldalert system over the next few weeks, said Keiji Fukuda, the WHOs assistant director-general of health security and environment. Dozens of cases in Chile and Australia indicate the virus is spreading in communities in the Southern Hemisphere.
U.K. Health Secretary Alan Johnson told the WHOs annual meeting last week that the organization should have greater flexibility in deciding whether the new H1N1 flu strain is sufficiently serious to raise the pandemic alert to the highest of its six-level scale. The virus causes fever and a cough in most people, unlike the H5N1 bird flu strain which influenced pandemic plans and is lethal in three out of five cases.
“We have a virus spreading which is significantly different to avian influenza,” Fukuda told reporters on a conference call from Geneva yesterday. “Countries are saying we want you to take a look at these criteria because if you apply them in the wrong way, they may not help us, in fact they may cause more difficulties.”
Forty-six countries have officially reported 12,954 cases, including 92 deaths, the Geneva-based WHO said yesterday. The tally excludes 47 new cases in the U.K., 45 in Chile, 42 in Australia, 8 in South Korea, 2 in Ireland and 1 in Singapore that were announced subsequently.
Among Chiles new cases, 19 resulted from community transmission in four regions, Osvaldo Sagrado, an official in charge of health-care networks at the ministry, said yesterday.
Cases Double
Global cases have more than doubled in the past two weeks as the pig-derived virus became established in countries outside North America, where it was discovered about six weeks ago. Still, the WHO wants to see more evidence of widespread community transmission before declaring the first influenza pandemic since 1968, Fukuda said.
A pandemic occurs when a new strain of flu to which few people, if any, have immunity spreads globally.
“We have an evolving situation in which a new influenza virus is clearly spreading but it has not reached all parts of the world and it has not established community activity in all parts of the world,” Fukuda said.
Disease Severity
Criteria for determining the pandemic alert level need to include disease severity among a broader range of indicators, health ministers from China, South Korea, Japan and the Association of Southeast Asian Nations said in a May 8 statement.
“Pandemic should refer to something that is severe and has a big impact on the economy and social activities,” Kamnuan said. “At this moment, the mental suffering and social worry is bigger than the physical disease itself.”
“If we announce the pandemic based on the geographical area only, then people will think this is a very bad situation and it will unnecessarily add to social and mental distress,” the official said.
The United Nations agency should have the flexibility to use emerging knowledge about the disease, rather than being driven by a purely “mechanistic approach,” the U.K. health departments Johnson told WHO Director-General Margaret Chan last week. The recommendation was supported by Japan, China and four other countries, the health department said.
Passed its Peak
In the U.S., the virus “may have passed its peak,” Anne Schuchat, the Centers for Disease Control and Preventions interim deputy director for science and public health, said yesterday on a conference call. Thats based on reports of flu- like illnesses that have returned to normal levels in most of the country, she said.
Flu levels remain high in New York, New Jersey and New England, Schuchat said. New, localized outbreaks may occur, she said. Still, the Atlanta-based agency is likely to turn its attention toward tracking H1N1s spread in the Southern Hemisphere, as well as preparing for any return in the north this fall, she said. The U.S. confirmed 6,764 cases in 48 states, the CDC said.
“It is very possible that this virus will continue to circulate and cause illness again next winter” in the U.S., Schuchat said. Whether it returns with more or less virulence “is not predictable right now.”