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Old 12-16-2010, 04:52 PM   #21
Rich66
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Re: Dealth Risk Found from Anemia Drugs

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Mom's treatment history (link)
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Old 02-03-2012, 02:05 PM   #22
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Patients May Die When Doctors Moonlight as Big Pharma's "Key Opinion Leaders"

As the crimson sun slipped into the gray Pacific Ocean, a multibillion-dollar drug deal took shape. A group of board-certified doctors greeted each other in a private room at a luxury hotel in California. The oncologists were big buyers of an anti-anemia drug called Procrit, sold by Ortho Biotech, a Johnson & Johnson (J&J) division. That Friday evening, the company toasted its top clients and their wives with bottles of Beaujolais, porterhouse steaks and free weekend accommodations.

The event could have been just another "grin and grip" affair, but there was a catch: J&J wanted to pump the sales of its biotech drug to beat its rival Amgen and its anti-anemia drugs. "The idea," as J&J drug rep Dean McClellan later explained, "was to get the docs to increase their Procrit dosage to 40,000 units."

There was just one problem. Regulators had approved a weekly drug dose of 30,000 units, and J&J was prohibited by the Food, Drug, and Cosmetic Act (FDAC) from marketing its drugs in unapproved ways. But the doctors could prescribe in any "off-label" manner they wanted. So, McClellan, a star rep and medical consigliere, led a "discussion" about high-dose experiments. Taking his cue, one physician explained how he routinely injected patients with 40,000 units of Procrit. Another oncologist pumped his people with 10,000 units for ten consecutive days - triple the approved amount. "That seems a little extreme," said McClellan, frowning.

"Oh no," the doctor said. "I haven't seen any side effects so far."

A few months later, Procrit sales hit the $1 billion mark, beating Amgen by a hair. The resort trip had certainly helped. But it was just one part of an expansive, long-running off-label marketing campaign, according to sales documents. Slowly but surely, oncologists around the country began administering so many high Procrit doses that, in time, the off-label therapy became the "community standard."

There were problems since insurers don't always reimburse doctors for off-label use. In fact, when Medicare refused to pay the Arizona Cancer Center, a huge client, for its high-dose Procrit injections, an Ortho manager ghost wrote a letter on behalf of its chief oncologist Daniel Von Hoff. After a few more company calls - ipso presto! - the center began receiving more than $1 million in Medicare payments for the illegal therapy. As McClellan claimed in a whistleblowing suit, the cancer market grew so saturated with high doses, that six years later the Food and Drug Administration finally approved them.

The decision might have been defensible had the 40,000-unit regime had been proven to be safe and effective. But independent research later revealed that cancer patients died sooner than expected, and company trials found an alarming number of dialysis patients suffered strokes and heart attacks. Meta-studies showed that 17 percent of patients died from the drug, and stories told of blood counts so high, patients actually spit up blood and choked on their own tumors. Turns out there was little scientific evidence that Procrit, and its cousins Epogen and Aranesp, actually helped people at any dosage.

Last summer, regulators announced that the drugs should be avoided entirely by most patients. "It turns out many people are better off taking placebos," said Dennis Cotter, president of Medical Technology and Practice Patterns, a nonprofit research institute.

What this illustrates is that drug companies can create entire cultures of over-prescribers for untested, even fatal indications, and that doctors can be easily corrupted. In light of a flurry of recent federal settlements for off-label marketing crimes, it also underlines how you, dear taxpayer, foot the bill for reckless marketing.

In the case of Procrit, the J&J unit formed advisory committees made up of academic physicians and clinical oncologists. These key opinion leaders (KOLs) were paid honoraria of at least $1,000 for every speech they delivered touting off-label use. McClellan selected some pliant clients to be the featured speakers. "Some guys wanted to give three or four speeches a weekend so they can get three or four thousand dollars," he said. A few actually did. Many talks were delivered at company "conferences" organized for other doctors, who earned hourly credits toward their annual continuing medical education (CME) units, required by state licensing boards. As if that wasn't enough, Ortho also paid physicians for their rooms, meals and transportation.

Ortho eventually assembled boards of KOLs who specialized in every type of cancer. According to sales documents, the goal was "to build thought leader endorsement [sic] to establish Procrit as standard of care," not just for approved indications such as AIDs and chemotherapy, but for cancer-related fatigue, depression, and other off-label indications.

These friendly prescribers were not Dr. Feelgood types working the tenderloin. They were distinguished professors from respected institutions such as John Hopkins University, Harvard Medical School, University of Chicago, Memorial Sloan-Kettering Cancer Center, Emory University Hospital, Cornell University, Long Island Jewish Medical Center, University of Texas MD Anderson Cancer Center, and others. Dr. Nicholas J. Vogelzang of the University of Chicago was a paid spokesman for the Fatigue Coalition, a group bankrolled by Ortho. Dr. John Glaspy of UCLA penned a seminal article in the Journal of Clinical Oncology that drew rosy conclusions about high-dose Ortho-sponsored studies.

Dozens of other doctors agreed to "influence their colleagues to use Procrit" for unapproved indications such as cancer-related fatigue. One was Dr. von Hoff, the director at the Arizona Cancer Center. He collected advisory fees and perks from not just Ortho, but from about 30 other pharmaceutical firms, earning directors' fees for sitting on several companies' boards. "When I saw how many shares he owned in biotech and drug firms, my jaw dropped," McClellan later said. Many others, like Dr. Jerome Groopman of Harvard Medical School, performed J&J-funded clinical trials. He was paid to sit on Procrit's "fatigue" advisory board and was quoted often in The New York Times extolling the drug, according to public records.

Groopman also penned a bestseller called "How Doctors Think." In it, he talks about the importance of talking with patients about their diagnosis and treatments. But Groopman doesn't explain what role Big Pharma checks and trips play in his own decision making. This is noteworthy since he goes on about the influence of high-pressure drug reps and the need for physicians to weigh scientific assessments against "going with your gut."

Clearly, even esteemed doctors were swayed by Procrit's marketers. In reviewing the basic science research behind these costly anti-anemia drugs, Dr. Charles Bennett of Northwestern University found that physicians and investigators who collected money from the two drug makers were "less likely to criticize the safety, effectiveness, or cost-effectiveness of drugs" and "more likely to endorse novel and less proven treatments" like off-label. No matter what prescribers say, they seem to have indeed been bought by golf trips, grants and banquets.

The overprescribing of anti-anemia drugs roared alongside an astonishing rise in American health care expenses. For several years, Procrit and the others topped Medicare's reimbursement list. By 2007, the drugs' domestic sales approached $11 billion a year. So far, US taxpayers have shelled out more than $60 billion over the past 20 years, reimbursing doctors, KOLs and hospitals for a drug that never worked as advertised.

McClellan's whistleblowing case may be in limbo. But many prestigious doctors will soon wind up in the confessional. Thanks to the Physician Payments Sunshine Act, doctors who accept speaking fees, meals, travel, stock options, or any other compensation from drug or medical device companies will soon see their names - and their gifts - revealed publicly on the web. The rule is part of the Patient Protection and Affordable Care Act, aka "Obamacare." Data collection was supposed to begin this January, but the first report won't appear until March 31, 2013. When that day dawns, patients will gain some insight into their treatments. Was that off-label prescription supported by scientific evidence; or did my doctor "go with his gut?" If so, how often was that gut filled by the maker of my medication?

From Kathleen Sharp's book, "Blood Feud: The Man Who Blew the Whistle on One of the Deadliest Prescription Drugs Ever."

"Dozens of other doctors agreed to 'influence their colleagues to use Procrit' for unapproved indications such as cancer-related fatigue. One was Dr. Von Hoff, the director at the Arizona Cancer Center. He collected advisory fees and perks from not just Ortho, but from about 30 other pharmaceutical firms, earning directors' fees for sitting on several companies' boards. 'When I saw how many shares he owned in biotech and drug firms, my jaw dropped,' McClellan later said. Many others, like Dr. Jerome Groopman of Harvard Medical School, performed J&J-funded clinical trials. He was paid to sit on Procrit's 'fatigue' advisory board and was quoted often in The New York Times extolling the drug, according to public records."

In 2010, Dan Von Hoff got the Karnofsky award from the American Society of Clinical Oncology (ASCO), which is sort of a lifetime achievement award for clinical research. This is a nuclear explosion for clinical oncology. I'm wondering who was involved in the Harvard side of it? Interestingly, it is the highest levels of academia who are most tainted. One in particular, Dan Von Hoff. These ivory tower docs were the culprits. Unfortunately, this will probably play out as one more cudgel to beat the more reasonable and gentle practitioners, who either largely avoided such abuse or were led down the path by the scholars, who will themselves skip out unfazed.
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Old 02-16-2012, 07:38 AM   #23
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Re: Dealth Risk Found from Anemia Drugs

The first article on platelets was very interesting. Glad this discussion was brought back up. If I read the article correctly, platelets could possibly play a role in metastais. When I started Navelbine in November my platelets started to rise, as my platelets went up, so did my tumor markers. My platelets were the highest they have been in over four years. I stopped Navelbine three weeks ago, and my platelets have come back down into the 200 range. I wonder if the increase of platelets were aiding my bone metatasis?

Amelia
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Old 02-16-2012, 09:12 AM   #24
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Re: Dealth Risk Found from Anemia Drugs

Amelia

Granulocyte colony-stimulating factor is one of the about 15 proteins known to activate endothelial cell growth and movement. At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessel growth.

A growth factor is about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. And blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction.

Colony-stimulating factor is a substance that stimulates the production of blood cells. Colony-stimulating factors include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and promegapoietin.

Examples:

White Blood count boosters = Neupogen (Filgrastim ), Neulasta (Pegfilgrastim), Leukine (Sargramostim)

Red Blood cell boosters: Procrit, Epogen (epoetin alpha, Erythropoietin), Aranesp (Darbepoetin)

The agents include epoetin alfa (Epogen, Procrit), epoetin beta (NeoRecormon), and darbepoetin alfa (Aranesp). Neulasta has to do with wbc (white blood cells) and pricrit has to do with rbc (red blood cells).

Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction.

The big difference is that white blood cells help fight infection, red blood cells transport oxygen throughout the body.

Erythropoiesis is basically a process where hemoglobin is synthesized, and eventually passes into the bloodstream.

Erythroprotein (EPO) is a natural substance made by the kidney.

Pharma EPO is a hormone that stimulates bone-marrow cells to produce red-blood cells.

Tumors create their own supply lines by secreting substances that stimulate the formation of new blood vessels. Pharma EPO is helping them along (growth factor).

Drugs that would stimulate white blood cells would not involve erythropoiesis (above). They would be involved with leukopoiesis, the process of making leukocytes, stimulated by various colony-stimulating factors (CSFs), and hormones produced by mature white blood cells.

Growth factors cause endothelial cell (the cells that line blood vessels) to produce chemicals that break down the nearby tissue and the extracellular matrix (the spaces between cells). Then the endothelial cells divide into more cells and begin building new blood vessels. Other elements, such as stromal cells (cells that form connective tissue), provide "structural support" for the new blood vessels.

Greg
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Old 02-16-2012, 12:59 PM   #25
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Re: Dealth Risk Found from Anemia Drugs

2/16/12 update:
Raised platelets reduce survival in ovarian cancer LINK

The crux of the research was nicely summed in the MD Anderson press release:
“Highly elevated platelet levels fuel tumor growth and reduce the survival of ovarian cancer patients.”

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Old 02-16-2012, 01:34 PM   #26
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Re: Dealth Risk Found from Anemia Drugs

The same MD Anderson researcher (Sood) said that patients whose tumors produced high levels of interleukin-8 (IL-8) protein had a worse outcome than those with less IL-8. Blocking expression of IL-8 in mouse models of ovarian cancer slowed tumor growth by reducing blood vessel growth.

IL-8 expression is elevated in many human tumors. Previous work indicated that the protein stimulates tumor growth, blood vessel development, and metastasis in animal models. Suppressing its activity with antibody therapy slowed tumor growth in those models.

In his previous study, Anil Sood, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston and colleagues tested 102 human ovarian cancer tumor samples for IL-8 expression. Of those, 43 (42 percent) had high levels of the protein and 69 (58 percent) had low or no IL-8 expression. The researchers found that the women whose tumors had higher levels of IL-8 were more likely to have advanced disease and poorer survival.

When the team used small-interfering RNAs to block IL-8 gene expression in animal models of ovarian cancer, they saw that tumor growth was substantially reduced. The slowed growth appeared to be due to less blood vessel development.

"Our findings suggest that IL-8 may be a potential therapeutic target in ovarian cancer," the authors write.

IL-8 and/or IL-6?
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