One of North America's leading cancer researchers has delivered a major blow against a group of chemotherapy drugs that are widely used in the treatment of cancer. These drugs, known as anthracyclines, include epirubicin (Ellence, Pharmarubicin), idarubicin (Idamycin), and doxorubicin (Adriamycin).

Adriamycin is currently a mainstay of breast cancer chemotherapy. However, earlier this year, at a private forum held at the American Society of Clinical Oncology (ASCO) meeting, Dennis Slamon, MD, PhD, director of the Revlon/UCLA Women's Cancer Research Program of the University of California at Los Angeles, revealed that his research had shown anthracyclines to be effective only in a small minority of women with breast cancer. For perhaps 90 percent of women, these drugs have little or no benefit - and carry the risk of some potentially very serious adverse effects, including cardiac damage.

For our previous reporting on Slamon's work, see our newsletter at:
http://www.cancerdecisions.com/070107.html

Slamon, whose research played a pivotal role in the development of the targeted anticancer drug Herceptin, presented dramatic new data on anthracyclines in mid-December 2007 at the San Antonio Breast Cancer Symposium.

Speaking at the conference, he remarked that continued use of anthracyclines on a "one-size-fits-all approach is just crazy and it's medically dangerous." According to his presentation, both retrospective and prospective data show that the anthracyclines only benefit women who have a specific tumor profile that includes an amplification of both the HER2 receptor and the topoisomerase IIa gene (Topo IIa). Such dual gene amplifications occur together in only 8 percent of breast cancer patients. This means that 92 percent of women who receive this toxic drug derive no benefit from it whatsoever.

"When we didn't have an alternative and when we didn't know how to identify the women who would benefit, it made sense to use the drugs," Slamon told the San Antonio gathering.

The anthracyclines - particularly Adriamycin - yield about a 5 percent improvement in overall survival, explained Slamon. But that is because they have a big effect in a small minority of patients, with no effect at all in 92 percent.

Some oncologists (such as Jerome Groopman, MD) have dubbed Adriamycin "the red death," because of its striking rose-red color and its potentially fatal side effects. Adriamycin and the other anthracyclines are especially damaging to the heart. Adriamycin's label contains this dire warning:

"Myocardial [i.e. heart muscle] toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The probability of developing impaired myocardial function… is estimated to be up to 20 percent at the highest doses. This toxicity may occur at lower cumulative doses in patients with prior mediastinal irradiation or on concurrent cyclophosphamide therapy or with pre-existing heart disease."

I think this FDA-sanctioned warning speaks for itself.

Slamon also discussed new data showing that when Herceptin was added to standard chemotherapy the results were as good as when Adriamycin was included. Essentially, the latter drug is unnecessary for all women who are candidates for Herceptin. Similar results have been seen in eight other studies.

Critics point to the fact that Slamon is a paid consultant for Genentech, the drug company which manufactures Herceptin. They also point out the fact that his data and conclusions have so far only been presented as an abstract, and as an informal discussion in the context of a meeting, rather than in the form of a paper published in the peer-reviewed medical literature. But given Slamon's status in the world of breast cancer research and treatment, his work, preliminary though it is, should have a major impact on oncologists' prescribing practices.

Eric Winer, MD, of Boston's Dana-Farber Cancer Center, who moderated the San Antonio Breast Cancer Conference session at which Slamon presented his data, told the Associated Press: "We are backing off on chemotherapy and using chemotherapy more selectively" (Marchione 2007). He further remarked: "It will make me very happy if we can get rid of Adriamycin and its inherent cardiac toxicity." But he stopped short of endorsing Slamon's attack on the anthracyclines. "I'm not ready to say that this is an agent that doesn't have a role - yet." Dr. Winer also said the debate over Adriamycin doesn't signal a "rift in the breast cancer community." Right. It's more like a chasm.

--Ralph W. Moss, Ph.D.

References:

Marilynn Marchione. Fewer Breast Patients May Need Chemo. Associated Press December 13th 2007; Accessed from:
http://news.yahoo.com/s/ap/20071213/ap_on_he_me/breast_cancer_chemo

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