Seminars in oncology
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A large number of new drugs have been approved over the past 10 years for the treatment of both common and rare gastrointestinal malignancies. Many other agents, however, have failed at a great cost of financial and patient resources. ⋯ Pharmaceutical companies must show therapeutic efficacy and achieve regulatory approval as well as success in the marketplace to recoup their investment. It is worth examining successful examples of drug development such as imatinib, delayed but eventually successful agents such as oxaliplatin, as well as failures such as SU-5416, and applying those lessons to current and future drug development.
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The widespread adoption of screening mammography has resulted in an increased incidence of ductal carcinoma in situ (DCIS), which now accounts for 20% to 30% of new breast cancer diagnoses. Despite treatment with combined lumpectomy and radiation therapy, up to 15% of women will experience an ipsilateral breast recurrence, with 50% of these recurrences containing invasive disease. There is also a 6% incidence of contralateral breast cancers in women treated for DCIS. ⋯ The benefit attributable to tamoxifen was confined to those tumors that were estrogen receptor (ER)-positive. However, adverse events, including endometrial cancer, thromboembolic events, and cataracts, are more common in older women. Tamoxifen should be considered as an adjunct to treatment for women undergoing breast-conserving surgery for ER-positive DCIS.
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Seminars in oncology · Dec 2006
ReviewAdjuvant therapy with aromatase inhibitors for postmenopausal women with early breast cancer: evidence and ongoing controversy.
Results of five major randomized trials have increased our understanding of the role of aromatase inhibitors in the adjuvant setting. Two of these trials, the Anastrozole or Tamoxifen Alone or in Combination (ATAC) trial and the International Breast Cancer Study Group's BIG 1-98 trial compared an aromatase inhibitor versus tamoxifen as initial hormonal therapy. Three other trial were designed as cross-over studies; the Intergroup Exemestane Study (IES) and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8/German ARNO 95 trial compared a crossover from tamoxifen to an aromatase inhibitor versus continued tamoxifen in women who had completed 2 to 3 years of tamoxifen. ⋯ Based on the results of these studies, the use of an aromatase inhibitor for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer has largely replaced the previous standard of 5 years of tamoxifen. Still unanswered, however, are questions regarding optimal sequencing, selection of aromatase inhibitor, and duration of treatment. This review will provide an overview of the major studies with an emphasis on these important questions.
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In 2006, approximately 38,890 patients in the United States will be diagnosed with kidney tumors. Roughly 90% of those will be renal cell carcinomas (RCCs). Of those patients, 30% will have metastatic disease at the time of diagnosis. ⋯ An improved understanding of the molecular basis of RCC has allowed for a more targeted approach to therapy. Several newer agents, including thalidomide, vitespin (heat shock protein [hsp] 96 vaccine), WX-G250, sorafenib, and sunitinib, are either currently under investigation in the adjuvant setting or being considered for future adjuvant trials. Here, we discuss the past, present, and future of adjuvant therapy for RCC patients at high risk for relapse following definitive surgical therapy.
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The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family that is abnormally activated in many epithelial tumors. Several mechanisms lead to the receptor's aberrant activation that is observed in cancer, including receptor overexpression, mutation, ligand-dependent receptor dimerization, and ligand-independent activation. Two classes of anti-EGFR agents are currently approved for the treatment of patients with cancer: cetuximab, a monoclonal antibody directed at the extracellular domain of the receptor, and gefitinib and erlotinib, oral, low-molecular-weight (MW), adenosine triphosphate (ATP)-competitive inhibitors of the receptor's tyrosine kinase. ⋯ Clinical and survival benefits with anti-EGFR agents have been demonstrated in additional tumor types such as head and neck and pancreatic carcinomas. New agents with clinical activity are entering the clinic and new combinatorial approaches with anti-EGFR agents are being explored. Major efforts are, belatedly, attempting to identify molecular markers that can predict patients more likely to respond to anti-EGFR therapy.