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Last Updated: Jun 15th, 2006 - 07:14:10 |
Cancer of the colon and rectum is the third most common cause of cancer deaths for both Black men and women, with death rates approximately 30 percent higher than among whites, and more than two times higher than for Asian American, American Indians, and Hispanics.
Explanations for these differences have included diagnosis of the disease at a later stage and having less access to screening tests for earlier diagnosis. But, results from a multi-center study in the United States and Canada suggest another possibility: response differences among Blacks to standard chemotherapy treatments for advanced colorectal cancer.
This finding, along with the emergence of BiDil - the first medication approved and marketed for treating specific racial and ethnic groups- add to tensions in medicine, especially as health disparities, genetic technology, and expanding pharmaceutical marketing are today’s major issues.
Dr. Richard M. Goldberg- chair of the multi-center study known as the Cancer and Acute Leukemia Group B (CALGB) gastrointestinal center committee, professor of medicine and hematology-oncology, division chief at the University of North Carolina at Chapel Hill, and associate director of clinical research at UNC Lineberger Comprehensive Cancer Center- explained, “The aim of this research was to compare African American with Caucasian patients with respect to their responses to the time it took for their cancers to become worse, and their overall survival. We also wanted to see if there was any difference in the side effects profile.”
Looking at the DNA
The 1,412 black and white participants who participated in the study had advanced colorectal cancer and were similar in gender, age-range, extent of disease, and prior treatment. Both groups were required to donate a tube of blood for DNA studies. Dr. Goldberg further described the procedure, saying, “We were looking at their DNA, focusing on minor differences called polymorphisms, or variations in DNA sequences that are present in specific genes in every cell in the patient’s body…The genes we were particularly interested in are those genes coding for key enzymes involved in drug activation, metabolism, and disposition.”
The study, which started in the 1990s, was conducted in 155 locations across the U.S. and in Canada. The patients were a subset of participants enrolled in a clinical trial that helped establish the value of the now-standard chemotherapy regimen known as FOLFOX4 - a combination of standard anticancer drugs 5-fluorouracil, leucovorin, and the new drug, oxaliplatin.
The trial assigned patients to one of three chemotherapy programs. Each program had patients receive two of three drugs- 5 Fluorouracil, irinotecan, or oxaliplatin. Even when all three treatment programs were analyzed together, and when each chemotherapy combination was analyzed separately, Blacks had a “significantly lower response rate” overall. The results of the three treatment arms showed Blacks had a 29 percent response rate while Whites had a 41 percent response rate.
However, Blacks fared better when it came to adverse side effects.
Dr. Goldberg noted, “African American had significantly less severe toxicity, mainly due to less severe diarrhea.” Toxicity refers to the discomfort experienced by a patient undergoing chemotherapy, as the drugs are actually toxins. Side effects include abdominal pain, changes in blood pressure, constipation, and diarrhea, among others.
Dr. Goldberg commented, “This study suggests that since African Americans don’t respond as well to these chemotherapies as Caucasians, but don’t have as much toxicity, we may not have arrived at the optimal strategy for their treatment. It would certainly be worth exploring other strategies, including dose-escalation.”
In addition, in an attempt to find differences in the frequencies of DNA polymorphisms, Goldberg and his colleagues executed genetic tests on a group of 500 participants. Dr. Goldberg said, “We looked at 21 genes that we knew were involved in transporting these drugs into the cell, converting them to active products, de-toxifying them and preparing them for excretion. And then we correlated the frequencies of polymorphisms in these genes with our clinical endpoints.”
They found that blacks and white had “significantly different frequencies of polymorphisms- variations in DNA sequences that are present in specific genes in every cells- in candidate genes coding for key enzymes involved in drug activation, metabolism, and disposition.”
Humans are 99 percent genetically identical
These findings, which were presented as an abstract on June 4 at the American Society of Clinical Oncology meetings in Atlanta, touch upon an issue that panelists at a Massachusetts Institute of Technology discussed in a conference regarding the emergence of race-and-ethnic-specific drugs. While Dr. Goldberg and his colleagues may have a case with their investigation on race-specific treatment for colorectal cancer, the argument stands as researchers and outspoken individuals point out that humans are 99% genetically identical. So, why should there be a drug such as BiDil, marketed to treat heart failure specifically in African Americans?
Jonathan Kahn, panelist at the MIT conference, and co-author of the abstracted titled BiDil: Race Medicine or Race Marketing, stated in the document, “The push to bring these drugs to market as a race-specific treatment was motivated by the peculiarities of U.S. patent law and a willingness to exploit race to gain commercial and regulatory advantage.”
In fact, Keith Ferdinand, M.D., panelist at the MIT conference and member of the Association of Black Cardiologists, could say that BiDil is a combination of two drugs that have long been recognized as beneficial to patients with heart failure, without any relevance to race or ethnicity.
In an interview with Jim Lehrer on NewsHour last year, he commented, “What should the labeling be? Should it be a medication that’s added to conventional medicine for treating heart failure only in blacks? I don’t really think so. That may be the label at that the FDA utilizes when it finally makes its recommendations. I think what it should say is the following: This drug has been shown to be beneficial when added to conventional modern therapy in patients who have moderate to sever heart failure and it was based on a study of 1,050 self-identified African Americans- period.”
Vivian Ota Wang, Ph.D., member of the FDA panel that voted unanimously for the approval of BiDil, said that she approved the drug because it proved beneficial to Blacks, but noted, “I am more hesitant to do the specific labeling mainly because I think it gives us a false sense of biological validity that its effectiveness is on a particular group of people who self-identified as Black…In fact, what we should be looking at are some of the underlying processes related to heart failure. For example, maybe the people who responded better were actually—their heart failure was due to hypertension versus coronary artery disease, and that we shouldn’t globally generalize it for all people.”
Old Racial Concepts
It is this generalization by BiDil that creates uneasiness among those in the African American community, who believe that genome research subtly reincorporates old racial concepts. Indeed, while the difference in genetic makeup among humans is barely recognizable, the socioeconomic disparities between Blacks and Whites are immense, and should these disparities not be the areas of consideration when treating patients?
Dorothy Roberts, faculty fellow at Northwestern’s Institute for Policy Research and author of Shattered Bonds: The Color of Child Welfare and Killing the Black Body: Race, Reproduction, and the Meaning of Liberty, argues that the “idea behind race-based pharmaceuticals discounts the importance of environmental factors in explaining difference in black and white patients’ experience of disease to market a technological fix based on supposed genetic difference.”
Roberts touches upon the dangers of race-based genetic research in her presentation at the Center for Genetics and Society symposium, “The Next Four Years, the Biotech Agenda, the Human Future: What Direction for Liberals and Progressives?”
She points out two dangers of race-based genetic research: using resources that could address socioeconomic causes of health disparities and reserving better therapies for white patients, as pharmaceuticals justify that drugs such as BiDil improve medical care for Blacks.
Roberts challenged the members of the symposium, saying, ‘I will wager any scientist here that after another decade of the most complex and well-financed research into the genetic basis of diseases, we will have to conclude that Black people’s health-indeed, everyone’s- would improve fare more by universalizing health care, equalizing the education system, cleaning up the environment, and reducing poverty. The future of most Black children hinges on the kind of society they are born into, not the genetic traits they are born with.”
Troy Duster, who served as Chair of the National Advisory Committee on Ethical, Legal and Social Issues of the Human Genome Project and was the keynote speaker at the MIT conference, shares similar thoughts as Roberts.
In an interview last year for the New York Times, he explained that while he is not against genome research, he is against “the way some biologists interpret it and act as it genetics has all the answers to medical problems that people in some ethnic groups suffer…this is the old nature versus nurture debate that’s been argued for eons. However, since the genomic revolution has gathered steam, it seems as if many scientists have stopped considering the nurture part…there’s been a recent tendency for geneticists to believe they are doing deep science when they look at race, genes, and disease. By looking at what’s in the blood, they avoid the messy stuff that happens when humans interact with each other.”
To further prove her point, Roberts referenced Kahn’s work in her presentation and stated, “it was the FDA’s initial denizl of approval to BiDil as a race-less drug that led its creator to reconceptualize it as a drug for Blacks, which then enabled it not only to get the FDA’s blessing, but also to raise venture capital, receive a lucrative patent, and launch a successful marketing campaign.”
Though the human genome says that we are all 99 percent the same, these controversial topics of race and ethnicity will remain, hotly debated and raised in the medicine and society again and again, until medical advancements allow for a race-and-ethnic-blind solution. Dr. Goldberg concluded, “Perhaps, in time, we’ll be smarter about how we prescribe drugs by doing an analysis of DNA ahead of time, thereby allowing us to individualize the most effective and tolerable drug therapy on a patient-by-patient basis.”
© Copyright 2004 by Career Communications Group, Inc.
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