Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Kudlowitz, David; Fm, Muggia

doi:10.1158/1078-0432.ccr-13-0572

Cited by 49 publications

(52 citation statements)

References 74 publications

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“…This model could be a good evaluation tool as it uses the same administration routine as in clinic. As expected, edema was increased by 33.5%, 35.0%, and 42.8% in the Taxotere™-treated groups (25,50, and 75 mg/kg, respectively) compared with the control groups that were treated with the same volume of saline ( Figure 4F). Surprisingly, no significant differences were observed in the Nufs-DTXtreated groups compared with the control groups.…”

Section: In Vivo Toxicity Of Nufs-dtxsupporting

confidence: 70%

“…Nufs-DTX and Taxotere™ (5 mg/mL) were diluted in sterile distilled water just before administration. Nufs-DTX and Taxotere™ (10,15,20,25, and 30 mg/kg) were iv injected once a day for 5 consecutive days. The animals' conditions (behavior, breath, hair, skin, and feces) were recorded and body weights were measured daily during toxicity test.…”

Section: Tumor Growth Delaymentioning

confidence: 99%

“…25,26 Hence, we used our Nufs-DTX to investigate whether DTX-induced neuropathy is attenuated. We used high doses in order to compare the toxicities of Nufs-DTX with Taxotere™.…”

Section: In Vivo Toxicity Of Nufs-dtxmentioning

confidence: 99%

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Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Choi¹,

Ko²,

Chung³

et al. 2015

IJN

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Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO 2 ), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.

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Section: In Vivo Toxicity Of Nufs-dtxsupporting

confidence: 70%

Section: Tumor Growth Delaymentioning

confidence: 99%

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Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Choi¹,

Ko²,

Chung³

et al. 2015

IJN

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“…2d). It can be concluded that in the model used here, paclitaxel treatment elicits foremost a degeneration of smaller unmyelinated sensory nerve fibers, thereby replicating basic clinical features of paclitaxel-induced peripheral neuropathy in humans (Kudlowitz and Muggia, 2013).…”

Section: Paclitaxel Induces a Predominant Small Fiber Sensory Neuropasupporting

confidence: 54%

Paclitaxel inhibits mRNA transport in axons

Bobylev

Joshi

Barham

et al. 2015

Neurobiology of Disease

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“…Paclitaxel (brand name Taxol ® ) is an effective antineoplastic agent that has been used in breast, ovarian, lung, head and neck cancers since the 1990s [1] . Severe dose-limiting painful sensory neuropathy has been found to be associated with paclitaxel chemotherapy and frequently leads to the termination of treatment and contributes to the deterioration of the quality of life and a decrease in the survival rate of patients.…”

Section: Introductionmentioning

confidence: 99%

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

et al. 2016

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Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg -1 ·d -1 ) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxelstimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxeltreated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and demonstrate the therapeutic potential of quercetin for treating this side effect.

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Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials

Cited by 49 publications

References 74 publications

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

Paclitaxel inhibits mRNA transport in axons

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

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