Herceptin Risks Are Being Ignored
1 CommentBy Ed Silverman // August 23rd, 2007 // 4:48 pm
Nearly six years after the breast-cancer treatment was first subsidized by the Australian government for late-stage sufferers, an analysis of all Australian women who have taken the Roche drug has found an urgent need to review guidelines. Despite a compelling body of evidence that Herceptin can increase the risk of cardiac failure, a University of New South Wales study has found that only 3 percent of those prescribed th med had their heart checked before and during treatment.
“We were all extremely surprised with the results,” Robyn Ward, a University of NSW professor, tells The Age. “We just couldn’t believe that people weren’t monitoring the safety of what was still a very, very new drug.”
The study, which reviewed 1,469 women who received the med between 2001 and 2005 and was published in the Journal of Clinical Oncology, found that some clinicians had ignored the warning labels altogether. Thirty-three women received the drug in combination with a type of chemotherapy known to heighten the risk of heart failure.
In all, 22 per cent of the women received Herceptin “off-label”, or as part of a combined therapy not approved by the Therapeutic Goods Administration. Ward says the results highlighted how important it is to monitor all new drugs, especially those that had been fast-tracked.
There are “emotional issues around things like cancer drugs and often there’s an incentive to release them as soon as any hint of efficacy is seen,” she says. “Herceptin is characteristic of a lot of these drugs: we only hear about the benefits and rarely about their downside or cost.”
Melbourne oncologist Ian Haines says patients needed to be kept up to date with findings about the risks of drugs and that Australia has a duty to scrutinize safety of new meds. “The longer we go with Herceptin, the more long-term heart problems we’re seeing. People (may) have died of heart disease rather than of their breast cancer…Australia has a unique opportunity because of our database of information.”
The University of NSW study also found that, with dosage based on a patient’s weight - about $21 million of taxpayer money - had been wasted because Herceptin was only sold in 150-millilitre vials. That’is nearly a quarter of all Herceptin dispensed over the period. At a cost of about $45,000 US per patient per year, Professor Ward says pressure had to be put on companies such as Roche, which makes Herceptin, to provide smaller doses.
Herceptin was subsidised in 2001 for women with late-stage breast cancer after it was shown to delay the spread of the disease. That was despite the advice of the Pharmaceutical Benefits Advisory Committee that the drug had not proven its safety or cost-effectiveness. In October last year, women with early-stage breast cancer were also allowed to start receiving Herceptin, as long as they tested positive for the relevant gene mutation that the drug targets.
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Although oral tyrosine kinase inhibitors, like Tykerb, offer patients a well-tolerated, conveniently administered alternative to intravenous (IV) therapy, Decisions Resources, one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues, found that oncologists are not yet ready to use Tykerb as a replacement for Herceptin. Ninety-one percent of surveyed oncologists stated that intravenous (IV) cancer therapies are more profitable than oral therapies. And fifty-eight percent of oncologists say they would favor IV Herceptin over oral Tykerb because administration of IV drugs remains an important source of income for their practices.
Selling cancer chemotherapy with concessions creates conflicts of interest for oncologists
http://www.healthyskepticism.org/news/2007/Jun.php
Aside from the financial incentives working here, there are marked differences between these two drugs.
Monoclonal antibodies like Herceptin and Erbitux are “large” molecules. These very large molecules don’t have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth.
Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, “small” molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent. Tykerb is one of the first oral agents with the potential to compete directly with the IV drugs which is both a high-volume and high-revenue part of office-based practices. But, is something more elemental going on? Does the drug even enter the cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate?
Also in regards to Herceptin, past studies have suggested a potentially very serious weakness in the drug, the problem with central nervous system (CNS) metastasis. According to research done at Dana Farber Cancer Institute, and published in the May 2003 issue of the journal Cancer, they identified central nervous system (CNS) metastases in women who receive trastuzumab-based (Herceptin) therapy for metastatic breast carcinoma. Central nervous system disease is defined as one or more brain metastases or leptomeningeal carcinomatosis (carcinomatous meningitis).
Central nervous system metastases was identified in 34% of patients at a median of 16 months after diagnosis of metastatic breast cancer and 6 months from the beginning of Herceptin treatment. Patients receiving Herceptin as first-line therapy for metastatic disease frequently developd brain metastases while responding to or stable on Herceptin. (Cancer 2003 Jun 15;97(12):2972-7)
Each of these new targeted drugs are not for everybody. Even when the disease is the same type, different patients’ tumor respond differently to the same agents. As the saying goes, “don’t throw out the baby with the bath water.” If a drug works extremely well for only 10% of cancer patients, identify which 10%. If one drug or another is working for “some” people (not average populations), then obviously there are others out there who would also benefit.