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Neurotoxicity Characterization Study of Nab-paclitaxel Versus Conventional Paclitaxel in Metastatic Breast Cancer

Fundacion Oncosur · 2012
ClinicalTrials.gov · Datasets · License: Public Domain · 2012
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breast-cancerneurotoxicity
Nanomedicines are currently being developed in the treatment of cancer due to their pharmacological advantages over traditional formulations; they provide a shorter infusion time and lower risks of hypersensitivity reactions associated with commonly used solvents. Nab-paclitaxel is a nanoparticle albumin-bound particle form of paclitaxel that is thought to exploit natural albumin pathways to enhance the selective uptake and accumulation of paclitaxel at the site of the tumour, thus reducing its diffusion to normal tissues. Nab-paclitaxel has been approved for the treatment of metastatic breast cancer patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline-containing therapy is not indicated. SPARC is a cysteine rich acid protein that is overexpressed in a broad proportion of solid tumours. Expression of this protein could sensitize tumour cells to antitumor activity of Nab-paclitaxel, due to its union through albumin-binding to this protein. First-line clinical trials have been developed with different Nab-paclitaxel regimens and also in combination with different chemotherapies and trastuzumab, showing a high level of efficacy. Toxicity profile of Nab-paclitaxel is well characterized with significantly less haematological toxicities compared with conventional paclitaxel. Nab-paclitaxel derived grade III neuropathy is short-lasting and more reversible than conventional paclitaxel-derived neuropathy, probably due to absence of Cremophor solvent, or due to paclitaxel itself. However there is still a lack of clinical and physiological characterisation of Nab-paclitaxel induced neuropathy. The current used tools for early detection and continuous evaluation of neurotoxicity are not optimal. Most used toxicity scales are limited, as they do not provide a detailed information of the severity of the neuropathy, its impact on quality of life, or physiopathology mechanisms. In addition, an inter-individual variabilit
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