FDA approves new drug for advanced breast cancer [Archive]

gdpawel

10-17-2007, 12:56 PM

Ixempra would be the first in a new class of chemotherapy drugs called epothilones. The medicine, which is injected, works by inhibiting tubulin, a protein that acts like a scaffold inside cancer cells and is necessary for their proliferation. Known generically as ixabepilone, the drug tries to stymie tumors by keeping cancer cells from replicating successfully. Ixempra would be used alone or in combination with Xeloda, in patients who have failed two or three other chemo drugs.

Bristol-Myers Squibb is trying to re-establish its prior prominence in oncology and got some good news with this approval. The FDA's approval of this drug harkens back to the old-school for breast cancer patients who aren't responding to other treatments. For use by women who have tried - without success - prior types of treatment. Why not give them the "right" drug or combinations the "first" time around.

The downside of Ixempra is that chemo that goes after dividing cells, also attacks healthy cells along with cancerous ones. Ixempra’s side effects include fatigue, hair loss and anorexia. Patients may experience a decrease in red blood cells, muscle pain, joint pain, the feeling of pins and needles in their fingers and toes, and in severe cases, inability to use their hands and feet fully. Does Taxol sound familiar?

Taxol was also a "natural" treatment. It inhibits the replication (mitosis) of cells. Targeting microtubles (a structure used in the division of cells) and stabilizes them to the extent that mitosis is disrupted. The problem is that it targets the fastest-growing cells, but it isn't specific to cancer cells. It also killed hair cells and cells in the stomach lining, leading to hair loss and nausea that are associated with chemotherapy.

According to the Office of Research, Florida State University, the picture wasn't all rosy for Taxol. As a cancer-fighter, Taxol had some serious drawbacks. For numerous cancer patients, the drug simply bounced off their tumors, doing little if any good. It was possible for patients to be resistant to it and develop a tolerance, limiting the drug's ability to fight future occurrences of cancer.

Scores of "new" cancer drug applications are for me-too drugs which might show only miniscule clinical improvement in trials, yet they somehow gain approval. So, for 1.6 months longer life (average population), patients can suffer from one or all of the above and still end up dead. Since they are marketed as if they were important new breakthroughs, they have very high prices. For most patients the total cost of a full course of Ixempra is expected to run from $18,440 to $23,050. Does Abraxane sound familiar?

Abraxane (a taxane) is a new form of Taxol. Abraxane does not need to be dissolved in the castor oil solution that Taxol does, and does not require special equipment to be given to patients. The delivery mechanism is different, however, they are basically the same drug. More of the women on Abraxane had numbness and tingling in their hands and feet. And more suffered nausea and vomiting, diarrhea, muscle and joint pain and anemia.

In academic centers, the patients are entered into clinical trials of square peg in round hole therapy. In the private sector, patients are treated with drugs which generate the most revenue for the treating oncologists, overtreat with infusion chemotherapy, and encourage the patient to receive 2nd, 3rd, and 4th line chemotherapy, regardless of the likelihood of meaningful benefit.

The academic center-based oncologists are misguided in not recognizing that they continue to try and mate a notoriously heterogeneous disease into "one-size-fits-all" treatments. They predominately devote their clinical trial resources into trying to identify the best treatment for the "average" patient, in the face of evidence that this approach is non-productive. However, such unsuccessful experiments will never be viewed as such by the people whose careers are supported by these kinds of experiments.

According to the National Cancer Institute's official cancer information website on "state of the art" chemotherapy in recurrent or metastatic breast cancer, no data support the superiority of any particular regimen. So it would appear that published reports of clinical trials provide precious little in the way of guidance.

There have been truly minuscule improvements as a result of adjuvant chemotherapy and the net benefit to the community of breast cancer patients in the real world isn't all that clear. And the criticism remains: All of the clinical trials resources have gone toward driving a square peg (one size fits all chemotherapy) into a round hole (notoriously heterogeneous disease).

http://www.medicalnewstoday.com/articles/85726.php

References:
NCI's Official Cancer Information Website on "State of the Art" Chemotherapy for Breast Cancer
Office of Research, Florida State University
PNAS 104: 11103-11108 June 20, 2007
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