The oncologist
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Review
Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy.
Standard oncological therapies, such as chemotherapy and cranial radiotherapy, frequently result in a spectrum of neurocognitive deficits that includes impaired learning, memory, attention, and speed of information processing. In addition to classical mechanisms of neurotoxicity associated with chemo- and radiotherapy, such as radiation necrosis and leukoencephalopathy, damage to dynamic progenitor cell populations in the brain is emerging as an important etiologic factor. Radiation- and chemotherapy-induced damage to progenitor populations responsible for maintenance of white matter integrity and adult hippocampal neurogenesis is now believed to play a major role in the neurocognitive impairment many cancer survivors experience.
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The taxanes docetaxel (Taxotere; Sanofi-Aventis U. S. LLC, Bridgewater, NJ) and paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) are highly active agents in metastatic breast cancer and may represent a safer alternative to anthracycline-based regimens when combined with the human epidermal growth factor receptor (HER)-2-targeted agent trastuzumab (Herceptin(R); Genentech Inc., South San Francisco, CA). ⋯ Results from two large, phase III trials that examined the addition of carboplatin to a taxane-trastuzumab doublet did not demonstrate a difference in survival with carboplatin. In one study, the addition of carboplatin to paclitaxel-trastuzumab therapy resulted in a higher response rate and longer progression-free survival time; in the second study, the docetaxel-trastuzumab and docetaxel-trastuzumab-carboplatin combinations were equally effective. Ongoing correlative studies of taxanes, as well as newer formulations such as nanoparticle albumin-bound paclitaxel, in combination with trastuzumab will inform clinical practice regarding the optimal agent, schedule, and use of these highly effective regimens.
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Chronic myelogenous leukemia (CML) is defined by the presence of the constitutively active tyrosine kinase breakpoint cluster region/Abelson (Bcr-Abl), which activates numerous signal transduction pathways leading to uncontrolled cell proliferation. The development of the Bcr-Abl-targeted imatinib represents a paradigm shift in the treatment of CML, because treatment with imatinib resulted in significantly better patient outcome, response rates, and overall survival compared with previous standards. Despite this advance, not all patients benefit from imatinib because of resistance and intolerance. ⋯ A large trial program showed that dasatinib is effective in patients previously exposed to imatinib and has a manageable safety profile in all phases of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, resulting in its approval. Nilotinib, an analogue of imatinib, also has demonstrated activity in a similar patient population. These agents and less clinically advanced strategies are discussed in this review.
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Thyroid nodules are common, with up to 8% of the adult population having palpable nodules. With the use of ultrasound, up to 10 times more nodules are likely to be detected. Increasing numbers of nodules are being detected serendipitously because of the rising use of imaging to investigate unrelated conditions. ⋯ The challenge remains in the management of nodules that fall under the "indeterminate" category. These may be subject to more surgical intervention than is required because histological examination is the only way in which a malignancy can be excluded. Surgery followed by radioactive iodine ablation is the mainstay of treatment for differentiated thyroid cancers, and the majority of patients can expect high cure rates.
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Certain studies in which erythropoiesis-stimulating agents (ESAs) have been given not with the aim of correcting anemia but to achieve higher target levels of hemoglobin have shown significantly poorer survival among treated patients. However, studies in which ESAs were administered with the aim of reducing the need for RBC transfusions in patients with chemotherapy-associated anemia demonstrate that the use of these agents is not associated with any adverse effect on survival when compared with placebo controls. We can therefore be reassured that using ESAs within the labeled indications will not adversely affect patient outcome.