gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
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 Posted: Fri Apr 08, 2005 3:24 am Post subject: Chemotherapy in Metastatic Breast Cancer |
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Chemotherapy in Metastatic Breast Cancer: Historical Accomplishment
In the March 15, 2003 issue of the Journal of Clinical Oncology, there was an editorial by V. Valero and G.N. Hortobagyl (J Clin Oncol 21(6): 959-962,'03) which reviewed all of the large, prospective, randomized trials published comparing the newer, taxane-based chemotherapy regimens. These authors concluded that none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at two years or less. This is precisely the same results which were being obtained 30 years ago.
In the September, 2002 issue of The American Journal of Oncology Review, there was a commentary by Lawrence N. Shulman, M.D., Vice Chair for Clinical Services/Adult Oncology, Dana-Farber Cancer institute (Harvard Medical School), Boston. His commentary described the complete lack of progress in the chemothereapeutic treatment of metastatic breast cancer since 1970.
The results of nearly 30 years of clinical investigation in the treatment of patients with metastatic breast cancer, neither standard or high-dose chemotherapy had done a great deal to improve the outcome of patients with this disease. For over the past 20 years, we relentlessly combined chemotherapy agents in various regimens with ever-increasing dose intensity and the survival for patients participating in these studies was exactly the same, less than two years. Not a hint of significantly improved survival.
Dr. Shulman noted that a retrospective comparison, well-characterized standard-dose database with a less well-characterized high-dose database suggested that there was increased early mortality for high-dose therapy. Highly selected patients whose tumors are responsive to chemotherapy can have long-term remissions from standard-dose chemotherapy. One large randomized trial showed no difference in survival for patients treated with standard-dose versus high-dose chemotherapy. The median survival for both groups was two years, and no subset of patients seemed to benefit from high-dose therapy.
Even if one were an optimist and concluded that the high-dose data suggested that a small subgroup of patients benefited from this approach, one must remember that the patients participating in these studies are already highly selected for age, performance status, response to induction therapy and other factors. At best, it must be helping only an incredibly small percentage of the patients with this disease.
Clearly, more effective therapies are desperately needed for women with metastatic breast cancer, and after 30 years of investigation aimed at intensified multi-agent chemotherapy, we should look for other avenues of study. The fact that regressions of breast cancer had no influence on overall survival must reflect the inadequacy of present-day chemotherapy. How the use of chemotherapy which induces responses in some patients, cannot have affect in overall survival? Does chemotherapy shorten survival of some patients, while prolonging the survival of others?
In an era of ever-increasing numbers of partially effective cancer therapeutics, there is an obvious need for technologies to better match treatment to a patient. In the field of chemosensitivity testing, there is substantial literature that has not been recently reviewed and which the vast majority of clinical oncologists are not familiar.
Approximately 10,000 individual patient specimens are currently being submitted for testing by more than 1,000 cllinical oncologists, surgeons and pathologists annually in the United States. The tests engender uninformed reactions and opinions from various clinicians within the referring medical centers. This is a timely and important topic for review, consideration and debate.
It is time (over-due) to set aside empiric one-size-fits-all treatment in favor of recognizing that breast, lung, ovarian and other forms of cancer represent heterogenous diseases, where the tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing the individual properties of each patient's cancer. |
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gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
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| Posted: Sat Apr 30, 2005 2:01 am Post subject: Re: Chemotherapy in Metastatic Breast Cancer |
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Neil Love, M.D. reports in a survey of breast cancer oncologists based in academic medical centers and community based, private practice oncologists. The academic center-based oncologists do not derive personal profit from the administration of infusion chemotherapy, the community-based oncologists do derive personal profit from infusion chemotherapy, while deriving no profit from prescribing oral-dosed chemotherapy.
The results of the survey show that for first line chemotherapy of metastatic breast cancer, 84-88% of the academic center-based oncologists prescribed an oral dose drug (capecitabine), while only 13% perscribed infusion drugs, and none of them prescribed the expensive, highly remunerative drug docetaxel.
In contrast, among the community-based oncologists, only 18% prescribed the oral dose drug (capecitabine), while 75% prescribed infusion drugs, and 29% prescribed the expensive, highly remunerative drug docetaxel. The existence of this profit motive in drug selection has been one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology.
This is not to imply that the academic centere-based oncologists are without their fair share of collective guilt. They were misguided in not recognizing that they were trying to mate notoriously heterogeneous diseases into one-size-fits-all treatments. They devoted 100% of their clinical trials resources into trying to identify the best treatment for the average patient, in the face of evidence that this approach was non-productive. However, such unsuccessful experiments will never be viewed as such by the thousands of people whose careers are supported by these experiments.
Henderson, et al, entered 3,100 breast cancer patients in a prospective, randomized study to compare cyclophosphamide/doxorubicin alone versus cyclophosphamide/doxorubicin plus Taxol (in the adjuvant, pre-metastatic setting). The results were microscopically positive, at best, and cannot begin to justify the enormous financial and human resources expended (while making no effort at all to test and improve methods to individualize treatment).
But these results changed the face of the adjuvant chemotherapy of breast cancer. Cyclophosphamide+Doxorubicin+Taxol became standard of care. Taxol recently went off patent. Now the thrust is to identify on-patent therapy which is microscopically better in clinical trials of one-size-fits-all treatment. Already, the community-based oncologists are migrating to Cyclophosphamide+Doxorubicin+Docetaxel (expensive/remunerative) so what was the purpose of doing that 3,100 patient prospective, randomized Henderson study?
http://patternsofcare.com/2005/1/editor.htm |
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