Archive for January, 2008
Overweight and obesity were associated with increased risk for many types of cancer.
The prevalence of obesity is increasing in developed countries. Almost one quarter of women in England are reported to be obese (BMI >30), and about one third are overweight (BMI, 25.0–29.9), whereas in the U.S., one third are obese and almost two thirds are overweight or obese. In the Million Women Study, English and Scottish women (age range, 50–64) self-reported demographic characteristics (BMI, age, geographic region, socioeconomic status, age at first delivery, parity, smoking, alcohol intake, physical activity, menopausal status, and use of hormone therapy) from 1996 through 2001. Investigators analyzed these data in relation to cancer incidence and mortality as reported in the National Health Service central registers.
Increasing BMI was associated with a significant positive trend in relative risk for adenocarcinoma of the esophagus (RR, 2.38); however, risk for squamous carcinoma of the esophagus decreased (RR, 0.26). Melanoma and stomach, colorectal, cervical, bladder, and brain cancers showed no variation in overall risk in relation to BMI. Premenopausal women (but not postmenopausal women who never used HT) had increased risk for colorectal cancer (RR, 1.61) or melanoma (RR, 1.62) with increasing BMI. However, increasing BMI was associated with a decreased risk for breast cancer in premenopausal women (RR, 0.86) and an increased risk in postmenopausal women (RR, 1.36). Endometrial cancer risk increased with BMI in both premenopausal (RR, 1.77) and postmenopausal (RR, 3.98) women. Other cancers for which risk increased with BMI were kidney cancer, leukemia, multiple myeloma, pancreatic cancer, non-Hodgkin lymphoma, and ovarian cancer. Lung cancer incidence decreased with increasing BMI (RR, 0.74); excluding smokers did not substantially alter the results. Overall, for 10 out of 17 specific cancer types examined, increasing BMI was associated with increased incidence and mortality.
Comment: The results of this large prospective study substantiate another potential health risk associated with being overweight or obese: cancer. According to these data, almost half of endometrial cancer and esophageal adenocarcinoma cases can be attributed to being overweight or obese. Menopausal status affects the relation between BMI and cancer risk, not only for hormonally related breast and endometrial cancers but also for colorectal cancer and melanoma. Women at risk for particular cancers because of personal or family history might be especially motivated by these findings to attain or maintain a BMI below 24.9.
Reeves GK et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: Cohort study. BMJ 2007 Dec 1; 335:1134.
January 30th, 2008
Some oncologists contend that patients undergoing chemotherapy and/or radiation therapy should not use food supplement antioxidants and other nutrients. Oncologists at an influential oncology institution contended that antioxidants interfere with radiation and some chemotherapies because those modalities kill by generating free radicals that are neutralized by antioxidants, and that folic acid interferes with methotrexate. This is despite the common use of amifostine and dexrazoxane, 2 prescription antioxidants, during chemotherapy and/or radiation therapy.
To assess all evidence concerning antioxidant and other nutrients used concomitantly with chemotherapy and/or radiation therapy, the MEDLINE® and CANCERLIT® databases were searched from 1965 to November 2003 using the words vitamins, antioxidants, chemotherapy, and radiation therapy. Bibliographies of articles were searched. All studies reporting concomitant nutrient use with chemotherapy and/or radiation therapy (280 peer-reviewed articles including 62 in vitro and 218 in vivo) were indiscriminately included.
Results: Fifty human clinical randomized or observational trials have been conducted, involving 8,521 patients using
beta-carotene; vitamins A, C, and E; selenium; cysteine; B vitamins; vitamin D3; vitamin K3; and glutathione as single agents or in combination.
Conclusions: Since the 1970s, 280 peer-reviewed in vitro and in vivo studies, including 50 human studies involving 8,521 patients, 5,081 of whom were given nutrients, have consistently shown that non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer. Furthermore, they enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue. In 15 human studies, 3,738 patients who took non-prescription antioxidants and other nutrients actually had increased survival.
(Altern Ther Health Med. 2007;13(1):22-28.)
January 29th, 2008
Extracts of black raspberries might protect Barrett’s esophagus patients against oesophageal cancer and also might shift premalignant oral lesions from progression to squamous cell carcinoma (SCC) back toward normal differentiation, Ohio State researchers reported at the AACR’s 6th Annual International Conference on Frontiers in Cancer Prevention Research.
Laura Kresty, PhD, assistant professor in the Ohio State University Cancer Chemoprevention Program, Columbus, reported that 58% of 20 Barrett’s oesophagus patients who ate a freeze-dried preparation of black raspberries daily for 26 weeks had a significant decline in mean urinary levels of 8-isoprostane, an indicator of global oxidative stress and DNA damage (abstract B34).
“Many of these patients had suffered from gastroesophageal reflux for a decade,” Dr. Kresty said at a press briefing. “Injury from acids results in generation of reactive oxygen species, which then cause damage. We tested this preparation in an attempt to decrease the ongoing oxidative stress in these patients.”
The take-home message, she said: “We need to increase fruit and vegetable consumption, and patients can do something to modify some pathways that lead to cancer.”
She recommended that the lyophilized black raspberry formulation be further studied in a randomized, placebo-controlled phase II trial.
An oral gel
Susan Mallery PhD, DDS, and her colleagues took a different approach. Her group tested a highly concentrated, bioadhesive black raspberry gel as a topical treatment for precancerous oral lesions (abstract B35). Dr. Mallery is a professor in the Department of Oral Maxillofacial Surgery and Pathology at Ohio State University’s College of Dentistry.
“The major problem with patients who have these premalignant lesions is recurrent disease that appears postop despite clear surgical margins,” Dr. Mallery said. “Black raspberries are full of anthocyanins, potent antioxidants that give the berries their rich, dark color, and our findings show that these compounds may have a role in silencing precancerous cells.”
This phase I/II trial included 20 patients with oral intraepithelial neoplasia (IEP) lesions and 10 normal controls. “There are lots of sugars and carbohydrates in black raspberries, and we wanted to control for risk of iatrogenic fungal infection,” Dr. Mallery said.
The “very motivated” participants applied the 10% (by weight) dried black raspberry gel four times a day to the target sites. Each patient served as his or her own internal control. None were smokers. The study continued for 42 days, the approximate amount of time necessary for 1½ cycles of surface epithelial turnover.
At the end of the study, Dr. Mallery said that comparison of pre- and post-treatment biopsies showed improvement (a decrease in lesion grade) in 35% of the patients, stable disease in 45%, and an apparent increase in lesion grade in 20%, but she suspects the latter is due to sampling bias.
More detailed examination showed decreased loss of heterozygosity (suggesting that cells were returning to a normal genetic state) and upregulation of cell differentiation markers.
Dr. Mallery said that the next step should be a longer (3-month), placebo-controlled, multicenter study. She also recommended further evaluation of berry gels for chemoprevention of oral IEP.
A more colorful diet
Navindra Seeram, PhD, MRSC, said that Dr. Mallery’s method is “a great approach” to many of the problems of taking a food into drug use because it overcomes the problem of degeneration of active components during the digestive process.
“The active compounds need to be in surface contact with the oral epithelium. If you are eating this berry, it spends a miserably short time in contact with the oral mucosa. This bioadhesive topical appears to be much better,” said Dr. Seeram, assistant professor in the Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston.
Dr. Seeram recently reviewed the cancer preventive potential of blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts (J Agric Food Chem 54:9329-9339, 2006).
A problem solved
Dr. Seeram also said that the lyophilized black raspberry preparation used in the study reported by Dr. Kresty solves another problem by permitting preparation of a large amount of standardized powdered extract that can be used in clinical trials.
He said that the studies reinforce the fact that “we should be eating more colors in our diet, particularly more berries.”
Cranberries are effective against urinary tract infections, Dr. Seeram said, and blueberries have anti-neurodegenerative effects.
“And now we see that black raspberries seem to have some anticancer activity. We need a rainbow of colors in our diets,” Dr. Seeram said.
Oncology News
January 2008 • Volume 17 Number 1
January 25th, 2008
Tumorigenesis or carcinogenesis is a multi-step process that is induced primarily by carcinogens leading to the development of cancer. Extensive research in the last few years has revealed that regular consumption of certain fruits and vegetables can reduce the risk of acquiring specific cancers. Phytochemicals derived from such fruits and vegetables, referred to as chemopreventive agents include genistein, resveratrol, diallyl sulfide, S-allyl cysteine, allicin, lycopene, capsaicin, curcumin, 6-gingerol, ellagic acid, ursolic acid, silymarin, anethol, catechins and eugenol. Because these agents have been shown to suppress cancer cell proliferation, inhibit growth factor signaling pathways, induce apoptosis, inhibit NF-κB, AP-1 and JAK-STAT activation pathways, inhibit angiogenesis, suppress the expression of anti-apoptotic proteins, inhibit cyclooxygenase-2, they may have untapped therapeutic value. These chemopreventive agents also have very recently been found to reverse chemoresistance and radioresistance in patients undergoing cancer treatment. Thus, these chemopreventive agents have potential to be used as adjuncts to current cancer therapies.
written by: Thambi Doraia and Bharat B. Aggarwalb
Cancer Letters
Volume 215, Issue 2, 25 November 2004, Pages 129-140 doi:10.1016/j.canlet.2004.07.013
January 24th, 2008
From the perspective of curative and preventive therapy, we have lost the war against cancer. Deaths from cancer are stable or increasing at 570,000 deaths in 2005.1 One in 3 people will get cancer in his or her lifetime.1 Given the average latent period of 30 years for solid tumours,2 17 million Americans are walking around with cancer that is somewhere along the continuum from initiation of a cancer cell to clinical manifestation of the disease.3 Clinical cancer care focuses almost entirely on eradicating the tumour through chemotherapy, radiation, or surgery, none of which addresses cancer early in the continuum of its natural history.
Emerging novel treatments, including vaccines and immunotherapy, hold promise. But are they enough? Are we focusing on late stage curative care and missing assessments and interventions that could change the landscape of cancer treatment and help those 17
million Americans prevent or reverse latent cancers?
In my oncology rotation in medical school, I asked my professor what percentage of cancers was related to diet and was shocked
by his answer—70%. Is there a different approach to cancer that allows for late stage interventions but asks a different set of questions based on a different set of assumptions? Rather than asking what is the right treatment for cancer, we might ask what genetic, lifestyle, and environmental factors trigger the development of cancer and what clinical strategies we can use to alter its trajectory.
Consider this fact: 16% of all cancers are new primary cancers in patients who have had cancer, not recurrences.4 This means that people who have cancer are more likely to get a second and independent cancer. Why is this so? Is it because of the toxic effects of the treatment of the first primary cancer, or is it something else? This is a compelling area for research and inquiry.
Another fertile area for inquiry and therapy might be based on an analysis of the etiology and mechanisms of cancer and how they influence the core physiological systems that determine our health. This might be called milieu therapy, or regulation therapy.
Rather than treating cancer per se, might we enhance immune function and surveillance through dietary and lifestyle changes, nutrient or phytonutrient therapies? Are there mechanisms that are common to most cancers, such as inflammation, altered hormone metabolism, oxidative stress, and impaired detoxification? With our current understanding of the mechanisms of cancer development and progression, we can reframe our treatment approach to include interventions that support the biological systems
that, when dysfunctional, allow the initiation, progression, and acceleration of cancer. The solution will come only through a systems approach. We have seen the flaws in reductionistic models of intervention, such as the CARET trials.5 Hundreds of millions of dollars were spent following the reductionist model of inquiry rather than a systems approach, with predictable and, unfortunately, negative
outcomes.6 Epidemiological evidence that vegetable consumption reduced cancer risk led to the assumption that betacarotene
was the “active agent.” This led to trials on thousands of smokers at risk for lung cancer using doses 100 times greater than what is normally consumed. The outcome of increased cancer risk among the treatment group should not have been a surprise— giving high doses of an antioxidant in an oxygen-rich environment (the lung), heated by smoke, led to increased oxidative
stress and the promotion of large amounts of reactive oxygen species, which facilitate cancer initiation and progression. A high dose of any one antioxidant can upset the equilibrium, leading to an uncontrolled free-radical chain reaction. This is what
happened in the CARET study. The lesson to be learned is not that vitamins don’t prevent cancer, but that single interventions in a complex physiology are likely to fail. The future of cancer care lies not in finding the best cocktail of chemotherapeutic agents, but in customizing treatments to correct patients’ individual imbalances. We must use our understanding of mechanisms of disease and physiologic and metabolic balance to design a treatment approach that uses diet, lifestyle, nutrient, phytonutrient, mind-body, and pharmacological
interventions to restore normal function and optimize gene expression patterns in the key systems that modulate cancer risk.
REFERENCES
1. American Cancer Society. Cancer facts & figures 2005. Available at: http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2005.asp. Accessed December 9, 2006.
2. O’Shaughnessy JA, Kelloff GJ, Gordon GB, et al. Treatment and prevention of intraepithelial neoplasia: an important target or accelerated new agent development. Clin Cancer Res. 2002;8(2):314-346.
3. Wattenberg LW. Prevention—therapy—basic science and the resolution of the cancer problem. Cancer Res. 1993;53(24):5890-5896.
4. National Cancer Institute. Tumors included in prevalence estimates. Available at: http://srab.cancer.gov/prevalence/methods.html. Accessed December 10, 2006.
5. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;88(21):1550-1559.
6. Burton GW, Ingold KU. Beta-Carotene: an unusual type of lipid antioxidant. Science. 1984;224(4649):569-573.
Mark A. Hyman, MD, is the editor-in-chief of Alternative Therapies in Health and Medicine. ALTERNATIVE THERAPIES, jan/feb 2007, VOL. 13, NO. 1 (Altern Ther Health Med. 2007;13(1):10.)
January 22nd, 2008
Each year, the American Cancer Society (ACS) estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. This report considers incidence data through 2003 and mortality data through 2004. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,444,920 new cancer cases and 559,650 deaths for cancers are projected to occur in the United States in 2007. Notable trends in cancer incidence and mortality rates include stabilization of the age-standardized, delay-adjusted incidence rates for all cancers combined in men from 1995 through 2003; a continuing increase in the incidence rate by 0.3% per year in women; and a 13.6% total decrease in age-standardized cancer death rates among men and women combined between 1991 and 2004. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. While the absolute number of cancer deaths decreased for the second consecutive year in the United States (by more than 3,000 from 2003 to 2004) and much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ.
Cancer Occurrence, Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA, USA.
CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.
January 20th, 2008
Generic drugs can save the consumer a lot of money. But some pharmaceutical manufacturers work aggressively to keep their market for a drug that goes off patent, limiting the availability of the generic brand. Here’s an example.
The term “generic drug” usually refers to a drug that has come off patent and is manufactured by one or more generic-drug companies in addition to the company that originally held the patent. Most generic drugs reach the market when the manufacturer’s patent on the product lapses. This is good news for consumers, because generics are less expensive than the brand-name drug but provide the same medical benefit. For instance, in 2006 the anticholesterol drugs pravastatin [Pravachol] and simvastatin [Zocor] went generic, offering people who switched to the generic form a savings of about 20% for the former and 10% for the latter, judging from the prices quoted on Drugstore.com. This is not good news for the original manufacturers, which lose the exclusive right to market a brand-name product.
An interesting article reported in The New England Journal of Medicine (Volume 355, page 1297) shows just how far big pharma will go to protect its interests. This article explains that an executive at pharmaceutical manufacturer Bristol-Myers Squibb agreed to make a secret cash payment of $40 million to Apotex, a Canadian generic drug company, to maintain its monopoly over sales of clopidogrel (Plavix) until 2011.
Plavix, a top-selling drug for preventing heart attacks and strokes, costs $4 per day. The generic would cost 20% less. In the end, the deal fell through and came under investigation by the U.S. Department of Justice, although a court injunction temporarily halted marketing of the generic version.
Such secret deals to keep cheaper generic drugs off the market are not uncommon, says an editorial in The New England Journal of Medicine. Manufacturers invent new drugs and take out multiple patents to protect their exclusive right to market them. When the patents start to expire, generic manufacturers often face years of legal battles to win the right to sell the drug. As a result, these companies may turn to special deals to avoid litigation. The generic manufacturer makes money by not selling its product. The brand-name company makes money by keeping its exclusive market for a while. Patients seldom know that they have lost money in the bargain.
Posted in Prescription Drugs on January 15, 2008
January 19th, 2008
