The oncologist
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Review
Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors.
Chemotherapy efficacy in patients with solid tumors is influenced by primary and acquired multidrug resistance (MDR). Epothilones represent a novel class of microtubule inhibitors with lower susceptibility to drug resistance and efficacy in taxane-resistant tumors. While other epothilones are currently under investigation, ixabepilone is the first epothilone B analogue approved by the U. ⋯ Ixabepilone is also active in chemotherapy-naïve and taxane-resistant hormone-refractory prostate cancer and platinum-resistant non-small cell lung cancer. Neutropenia and peripheral sensory neuropathy are the most common adverse events associated with treatment. This review discusses the challenges of MDR and the data that support the use of epothilones in this setting, focusing on ixabepilone.
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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.