The National Cancer Institute (NCI) has issued a very negative report on the drug Adriamycin (doxorubin) as well the other anthracycline drugs (epirubicin and idarubicin). As we reported here in 2007, prominent oncologists had begun to warn their colleagues and the public that use of this toxic class of drugs was unnecessary in as many as 92 percent of the breast cancer patients who received it. This point of view has now been given powerful support by a new Canadian study in the Journal of the National Cancer Institute (O'Malley 2009), with an accompanying editorial by Dr. Slamon (Slamon 2009).
The authors of the new article studied 438 tumor specimens from premenopausal women who had node-positive breast cancer and were given adjuvant chemotherapy after surgery. All the women received either a regimen known as "CEF" which contained, in addition to the standard drugs cyclophosphamide and 5-FU, epirubicin (an anthracycline); or they received an older regimen, "CMF" which contained, in addition to cyclophosphamide and 5-FU, the non-anthracycline methotrexate.
Scientists then looked for the presence or absence of certain markers on the cancer cells, called TOP2A and HER2. Their key finding was that patients whose tumors showed changes in these markers did indeed survive longer after receiving CEF (the anthracycline-containing regimen) than those treated with CMF. But they also showed that patients who did not have TOP2A changes had no significant improvement in survival (O'Malley 2009).
As Slamon commented in his accompanying editorial: "This report is the latest in a series of publications that question the generalized assumption that there is an incremental benefit to all breast cancer patients who receive anthracycline-based adjuvant therapy as opposed to non-anthracycline-containing adjuvant therapy" (Slamon 2009).
Slamon's remarkable editorial is available free of charge at the JNCI Web site. I urge all readers who are seriously interested in this question to study it carefully (link below). It contains much fascinating information on how the anthracyclines became part of the standard of care for adjuvant breast cancer chemotherapy.
Why does all this matter? Even in the world of toxic chemotherapy, Adriamycin (and its fellow anthracyclines) are notoriously dangerous: Slamon refers to the "well-known, long-term, and life-threatening problems associated with anthracyclines" (Slamon 2009). These adverse effects include cardiac toxicity including congestive heart failure as well as bone marrow dysfunction, including acute leukemia and myelodysplasia. These serious adverse effects have long been known. However, Slamon now presents data showing that "longer follow-up...of breast cancer patients who received adjuvant anthracyclines for their breast cancers indicates that our initial assessments may have underestimated these long-term toxicities" (Slamon 2009). In other words, the news about the long-term effects of anthracyclines is worse than we thought.
Slamon makes the further point that earlier assessments of the risks and benefits of adjuvant chemotherapy lumped all patients together in a rather crude way. "We now know that the molecular diversity of human breast cancers is much more complex and that clinical benefits derived from various systemic therapeutic interventions can be profoundly affected by the molecular subtype of the disease" (ibid.)
Since 2007 he has been courageously warning about the danger of the anthracyclines and calling for individualizing cancer treatment based on molecular characteristics of the tumor. I wholeheartedly agree. But I would argue that the issue is even larger. Oncology (like modern medicine in general) has a tendency to put patients into cookie cutter molds. The reason may be economics - it's more cost-effective to treat patients en masse with minimal time spent dealing with their individual characteristics.
But modern science (not to mention ancient humanism) tells us that each person is different, and that treatment should be individualize based on all aspects of the person. The molecular characteristics of the tumor are one important new part of that. But I would argue that this individualization should include chemosensitivity testing of tumors, the creation of autologous vaccines, and a more holistic approach that takes into account the psychological and social needs of the patient.
the above article is courtesy Ralph Moss, PhD.
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