Increased Pilot Studies Into Dietary Modifications and Cancer One of the most frequently asked questions for oncologists by patients diagnosed with cancer is whether or not diet will make any difference to their condition. "Answers to this question tend to be vague," point out Dr. Andreas Gescher and colleagues at the Medical Research Council's Department of Oncology, University of Leicester, Leicester, England. However, such questioning of doctors will not go away because of widespread publicity about diet in cancer, and the role of dietary modification in the prevention of cardiovascular disease. Dietary intervention is not new-pregnant women are always advised of the proven benefits of taking folate to prevent neural-tube defect of the fetus. As both conditions have a latency of many years before clinical diagnosis, "it is therefore reasonable to postulate that dietary components may prevent cancer from reaching its invasive and metastatic stages," the authors continue in their detailed review of research into dietary factors and cancer. Almost every month, new insights into the mechanisms by which dietary constituents may prevent cancer are published, and targets such as kinases, telomerase, cyclooxygenase-2, triggers of apoptosis, and transcription factors AP1 and nuclear factor kB are among the cellular targets. "Yet more robust mechanistic insights are required, that will allow characterisation of the effects operative at physiologically relevant concentrations," the clinicians add. A recent and major disappointment to investigators into dietary constituents, for example, have been two large trials that failed to detect any benefit of beta-carotene to decrease incidence of lung cancer in about 50,000 individuals, and the suggestions that in high-risk groups of smokers, and workers occupationally exposed to asbestos, the intervention increased the risk of developing the disease. "Subgroup analyses of these two trials showed that the risk of lung cancer was highest among individuals who continued to smoke at least 20 cigarettes per day and among those in the highest quartile of alcohol consumption," the authors continue. Clinical investigators have now swung towards pilot studies, which have been part of the US National Cancer Institute's prevention research programme for most of the past decade. "The lessons learned from the clinical trials of beta-carotene have modified the approach adopted in the development of the red tomato constituent lycopene, another carotenoid with putative chemopreventive properties, especially with respect to prostate cancer," Dr Gescher and colleagues continue. In contrast to the paucity of pharmacological knowledge on beta-carotene when clinical trial of that agent started, there is now much information on the mechanisms of chemopreventive activity and pharmacology of lycopene. Already there are definite benefits which have been found for some agents. Results for folate, which is already established in the chemoprevention of fetal neural-tube defects, are promising. Studies suggest a lower incidence of colorectal cancer among individuals with the highest intake of dietary folate, whereas people with diets low in folate, or with high alcohol intake, seem to have an increased risk of colorectal adenomas and carcinomas. Agents such as curcumin, derived from tumeric, and tea catechins also are among a number of dietary agents under early clinical investigation. The researchers point out that "there are currently no definite answers to questions posed by patients and at-risk individuals to oncologists, concerning diet or dietary supplements. Nevertheless, the increasing amount of literature on diet-derived cancer chemopreventive agents is starting to allow inferences to be made, which will contribute to the scientific basis of sound advice." Dietary constituents should be developed in a structured design, incorporating parallel preclinical studies of the food source and the isolated agent in terms of efficacy, toxicity, biological mechanisms, and pharmacokinetics. Preclinically, the food source and the isolated agent should be studied in parallel. One or the other should then be selected for further development, on the basis of efficacy and toxicity data. Clinicians conclude that "the selected intervention should be tested in pilot clinical studies that precede formal phase I-III evaluation in suitable populations. The challenge is considerable, but the potential rewards are enormous." Lancet Oncol 2001; 2: 371-79. 06/05/2001 09:27:30 AM By Harvey McConnell Thanks to Doctor's Guide (docguide.com) Lancet Oncology Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.