Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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A number of reports have documented the apparent increasing popularity of complementary and alternative medicine (CAM) among cancer patients. Unfortunately, there are limited available published data regarding the potential toxicity of a variety of CAM strategies. ⋯ It is important that oncologists are aware of what nonprescription CAM medications are being taking by their patients and have a basic understanding of the potential toxicities of these agents.
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STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose selection, optimizing therapy, and predicting response, as are possible mechanisms of resistance to STI571. Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies are explored.
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Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. ⋯ Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.
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Lung cancer is the leading cause of cancer deaths in the United States and the world, with grim incidence and mortality figures underscoring the need for new approaches, such as chemoprevention, for controlling this disease. There have been definitive, randomized, controlled lung-cancer chemoprevention trials in the three chemoprevention trial settings: primary (healthy high-risk [eg, smokers]), secondary (premalignant lesions), and tertiary (prevention of second primary tumors in previously treated patients), all of which produced negative (either neutral or harmful) primary end point results. ⋯ A major area of lung cancer research is molecular epidemiologic study of highest smoking-related risk based on the interactions between tobacco carcinogens, genetic polymorphisms involved in activating and detoxifying these carcinogens, and host-cell efficiency in monitoring and repairing tobacco carcinogen-DNA damage. The future of lung cancer chemoprevention will rely heavily on molecular studies of carcinogenesis and drug mechanisms to develop novel chemopreventive targets and drugs, risk markers, and surrogate end point biomarkers; new preclinical drug-testing models; novel imaging techniques for monitoring agent activity; and molecular epidemiologic risk models for identifying the highest-risk current and former smokers.
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Two prominent and timely issues in lung cancer screening are discussed in this article. First, findings from extended mortality follow-up of participants enrolled as part of the Mayo Lung Project are reviewed. ⋯ Given the absence of lung cancer mortality data for spiral CT, it is concluded that such activities should not be advocated at this point in time. The Lung Screening Study, an ongoing randomized controlled trial of lung cancer screening with spiral CT, also is described.