Seminars in oncology
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Seminars in oncology · Apr 2008
ReviewPreclinical investigations with epothilones in breast cancer models.
The epothilones constitute a novel class of microtubule inhibitors that act like the taxanes by hyperstabilizing tubulin polymerization, thus disrupting functioning of the mitotic spindle. Natural epothilones produced by myxobacteria, and second- or third-generation partially or fully synthesized analogs, have been explored as cancer chemotherapy agents to replace or follow the taxanes. ⋯ Comparable antitumor activity has been demonstrated against nude mouse xenografts of paclitaxel-sensitive and -resistant breast cancer lines. Additionally, some analogs have reduced toxicity or increased water solubility that may permit oral administration, while others with enhanced tissue penetration show promise in animal models of breast cancer brain or bone metastasis and may provide benefits in patients with poor-prognosis advanced breast cancer.
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Seminars in oncology · Dec 2007
ReviewRandomized adjuvant therapy trials in melanoma: surgical and systemic.
The utility of adjuvant surgical procedures in the management of primary melanomas has been evaluated in a large number of phase III randomized trials. These trials have shown that wide margins, elective lymph node dissection, sentinel lymph node (SLN) biopsy, and prophylactic isolated limb perfusion (ILP) do not improve survival but may improve locoregional control. Based on the claim of providing a survival benefit, these surgical procedures cannot be considered standard of care in the routine management of primary melanoma. ⋯ Interferon (IFN) has an effect on relapse-free survival but not on overall survival. Thus its impact is judged by many to be too small to be considered standard of care. The population of patients that can benefit from IFN needs to be better defined by identifying new biomarkers by genomic and proteomic studies, which are ongoing.
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Brain metastases are the most common intracranial tumors in adults and source of the most common neurological complications of systemic cancer. The treatment approach to brain metastases differs essentially from treatment of systemic metastases due to the unique anatomical and physiological characteristics of the brain. ⋯ Aggressive intervention may be indicated for selected patients with well-controlled systemic cancer and good performance status in whom central nervous system (CNS) disease poses the greatest threat to functionality and survival. In this review the respective roles of surgery and radiosurgery, patient selection, general prognostic factors and tailoring of optimal surgical management strategies for cerebral metastases are discussed.
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Seminars in oncology · Apr 2007
ReviewMolecular alterations associated with bladder cancer progression.
Clinically, superficial tumors (stages Ta, Tis, and T1) account for 75% to 85% of bladder neoplasms, while the remaining 15% to 25% are invasive (T2, T3, T4) or metastatic lesions at the time of initial presentation. More than 70% of patients with superficial tumors will have one or more recurrences after initial treatment, and about one third of those patients will progress and eventually die of the disease. New methods are needed to identify and monitor patients presenting with "high-risk" superficial tumors likely to develop into invasive carcinoma. ⋯ The concept of alterations affecting "genetic pathways" is becoming more than just a molecular biology exercise. The challenge is to evaluate such targets for therapeutic development, as well as to translate progression and outcome biomarkers into improved clinical management. Integration of data generated from in-depth clinical evaluation, histologic tumor characteristics, and validated biomarkers could provide highly accurate, predictive tools for management of the bladder cancer patient.
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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.