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What Doctors Don't Tell You

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July 2020 (Vol. 5 Issue 5)

Avastin: Bad News for the Brain

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Avastin: Bad News for the Brain image

It's no giant secret that chemotherapy is a knife-edge approach to healing-you take the drugs in the hopes that they will kill the cancer without killing you first

It's no giant secret that chemotherapy is a knife-edge approach to healing-you take the drugs in the hopes that they will kill the cancer without killing you first.

However, new evidence has revealed that the side-effects of chemo drugs have been grossly underestimated. A number of different types of chemo-therapy are now known to cause far more problems than were previously thought-mainly affecting the brain.

The first alert arrived from the US drugs watchdog, the Food and Drug Administration (FDA), which recently discovered that Genentech's drug Avastin (bevacizumab) causes bleeding in the brain and deterioration of nasal tissue. The agency found that Avastin can cause a rare condition called 'capillary leak syndrome', which leads to seizures, blindness, headaches, and other visual and neurological disturb-ances. It also causes small holes to appear in the cartilaginous septum that separates the nostrils. Eventually, this can cause a nasal discharge, as well as bleeding and deterioration of the tissues of the nose.

The drug is currently approved for use as a companion drug in the treatment of colorectal cancer. But Genentech is seeking to widen its approval to include other cancers, such as breast cancer, particularly as this will assure its stockholders-such approvals would mean that patients will be taking two-thirds more of the drug, worth about $90,000 per patient.

Disclosure of the capillary side-effect first appeared last year, when The New England Journal of Medicine published letters showing evidence of the adverse effects. The FDA now requires Genentech to include a warning in its patients' product inserts regarding bleeding in the brain and deterioration of nasal tissue.

Genentech counters with claims that less than 0.1 per cent of some 60,000 patients treated so far with Avastin have suffered from this side-effect. Furthermore, the condition is reversible when it does develop.

Nevertheless, this was one of the first pieces of evidence showing that chemo can cause damage to the brain. And this disclosure was swiftly followed by evidence showing that all chemo appears to change the way in which
the brain works and may be harmful to memory in some cancer patients - a problem called 'chemobrain' (Breast Cancer Res Treat, 2006 Sep 29; epub ahead of print).

In the study, short-term memory tests were given to 21 women who'd had breast-cancer surgery, 16 of whom had had chemotherapy up to a decade earlier. The researchers then took PET (positron-emission tomography) scans of the women's brains, and discovered that cognitive function was reduced, especially in the part of the brain call-ed the 'basal ganglia'. The women appeared to have to work harder when attempting to remember information on the memory tests.
Those women who had not received chemotherapy showed no evidence of such changes in brain function.

Although this study was small, other, earlier research suggests that from 25 to 82 per cent of breast-cancer survivors given chemotherapy suffer from chemobrain, with reports of for-getfulness and general brain 'fog'. Most of the studies concerned breast-cancer victims, probably because of their high survival rate. Nevertheless, chemobrain affects patients with any kind of cancer so long as they have had chemo.

Considering that some 10 million people in the US alone have under-gone chemotherapy, these effects on the brain have vast implications.

And now, new evidence shows that women under 63 receiving chemo-therapy as follow-up for breast cancer may experience even worse side-effects than previously reported in the studies.

A new review, conducted by the Dana-Farber Cancer Institute and Harvard Medical School, has examined a database of medical claims made by more than 7000 women with breast cancer who had medical insurance between January 1998 and 2002.

The claims were divided into two cohorts: one comprised those who had received chemo within 12 months of surgery; the other included those who had not.

The women receiving chemo were more likely to develop side-effects that required emergency hospitalization; these included fever, infection, nausea, diarrhoea, malnutrition, low white cell or platelet counts and dehydration.

The review also discovered that these eight side-effects, all related to chemotherapy, were far more common than had been reported in large clinical trials (J Natl Cancer Inst, 2006; 98: 1108--17).

The breast-cancer studies are ironic in that chemotherapy is simply a just-in-case treatment for breast cancer. Chemo is not thought to be effective for breast cancer and, originally, it was only administered to breast-cancer patients after it had spread to other parts of the body. It is now increasingly used to lower the risk of recurrence after surgery.
The study also found that chemo is more expensive. Women undergoing chemotherapy spent nearly $20,000 more in healthcare costs than women opting for surgery alone.

Ironically, Avastin had recently had its tarnished reputation revived with the results of a pilot study from Duke University showing that the drug slows the growth of gliomas, the most common and deadliest form of brain cancer. Avastin delayed the growth of gliomas for up to three months longer than other therapies (Clin Cancer Res, 2007; 13: 1253-9).

Despite problems with deep venous thromboses or pulmonary emboli, and one case of an arterial ischaemic stroke, the Duke University scientists managed to persuade the FDA to proceed with the study.

According to Dr James Vreden-burgh, the brain-cancer specialist at Duke's Preston Robert Tisch Brain Tumor Center who led the study, the risk of bleeding may be slightly increased with Avastin, but it's very difficult to tell because about 40 per cent of brain-tumor patients develop bleeding problems anyway.

As with so many instances of drug-related side-effects, the adverse effects of chemo can always be passed off as
a side-effect of the disease.

Other side-effects of Avastin

  • Slow or incomplete wound-healing
  • A higher risk of stroke or heart problems (blood clots)
  • Severe hypertension
  • Kidney dysfunction
  • Nervous system damage
  • Vision disturbances
  • Congestive heart failure
  • Nosebleed
  • Hypertension (high blood pressure)
  • Protein in the urine, a possible sign of kidney dysfunction
  • Weakness
  • Reduced white blood cell count
  • Pain
  • Diarrhoea
  • Gastrointestinal (GI) perforation.

Lynne McTaggart

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