Peripheral nerve damage associated with administration of taxanes in patients with cancer

Argyriou, Andreas A.; Koltzenburg, M; Polychronopoulos, Panagiotis; Papapetropoulos, Spiridon; Kalofonos, Haralabos P.

doi:10.1016/j.critrevonc.2008.01.008

Cited by 216 publications

(174 citation statements)

References 79 publications

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“…As paclitaxel neurotoxicity is dose-dependent, 13 we calculated the accumulated paclitaxel dose that produced clinically relevant neurotoxicity, rather than just evaluating the presence or lack of neurotoxicity at the end of the treatment. We confirmed that the more dose intense paclitaxel schedule of 80-90 mg m À2 weekly was a risk factor for the neurotoxicity 8,9 and, although previous results concerning age are inconclusive, 12,13,40 we found that patients below 50 years developed greater neuropathy (Supplementary Figure 1).…”

Section: Discussionsupporting

confidence: 82%

“…6,7 Neurotoxicity, which has become the dose-limiting toxicity of paclitaxel, exhibits substantial interindividual variability. This toxicity is dose-dependent and more frequent in weekly paclitaxel regimens, 8,9 in patients with diabetes, previous neurotoxic chemotherapy treatments and in patients with pre-existing neuropathies. 10,11 Age and gender might also be risk factors [11][12][13] and decreased levels of plasma nerve factors might have a role in the neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity

et al. 2010

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Neurotoxicity is one of the most relevant dose-limiting toxicities of the anticancer drug paclitaxel. It exhibits substantial interindividual variability of unknown molecular basis, and represents one of the major challenges for the improvement of paclitaxel therapy. The extensive variability in paclitaxel clearance and metabolism lead us to investigate the association between polymorphisms in paclitaxel elimination pathway and neurotoxicity. We selected 13 relevant polymorphisms in genes encoding paclitaxel metabolizing enzymes (CYP2C8, CYP3A4 and CYP3A5) and transporters (organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and P-glycoprotein) and genotyped them in 118 Spanish cancer patients treated with paclitaxel. After adjusting for age and treatment schedule, CYP2C8 Haplotype C and CYP3A5*3 were associated with protection (hazard ratio (HR) (per allele) ¼ 0.55; 95% confidence interval (CI) ¼ 0.34-0.89; P ¼ 0.014 and HR (per allele) ¼ 0.51; 95%CI ¼ 0.30-0.86; and P ¼ 0.012, respectively) and CYP2C8*3 with increased risk (HR (per allele) ¼ 1.72; 95%CI ¼ 1.05-2.82; and P ¼ 0.032). In each case, the allele causing increased paclitaxel metabolism was associated with increased neurotoxicity, suggesting an important role for metabolism and hydroxylated paclitaxel metabolites. We estimated the HR per paclitaxel-metabolism increasing allele carried across the three polymorphisms to be HR ¼ 1.64 (95% CI ¼ 1.26-2.14; P ¼ 0.0003). The results for P-glycoprotein were inconclusive, and no associations were observed for the other genes studied. The incorporation of this genetic data in treatment selection could help to reduce neurotoxicity events, thereby individualizing paclitaxel pharmacotherapy. These results warrant validation in independent series.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity

et al. 2010

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“…The incidence of paclitaxel-induced neuropathy ranges from 20% to 70% of patients (24,25). Mechanisms include disruption of axonal transport (26,27), mitochondrial damage (28)(29)(30), altered ion channel activities (31), and neuronal inflammation (32,33).…”

Section: Discussionmentioning

confidence: 99%

Integrating Image-Based High-Content Screening with Mouse Models Identifies 5-Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy

Chen

Sun

Chen

et al. 2015

Molecular Cancer Therapeutics

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Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. This study aimed to discover potential neuroprotective drugs for paclitaxel-induced neurotoxicity. An imagebased high-content platform was first developed to screen for potential neuroprotective drugs. The screening system comprised of automated image acquisition and multiparameter analysis, including neuronal viability, neurite outgrowth, and synaptogenesis. By this platform, we obtained a candidate list from compound libraries. In the drug screening from compound libraries of ion channel ligands, REDOX and GABAergic ligands, 5-hydroxydecanoate (5-HD) exhibited the most significant neuroprotective effects against paclitaxel-induced neurotoxicity in both cortical and dorsal root ganglion (DRG) neurons. In mouse behavioral tests, 5-HD restored the thermal sensitivity and alleviated mechanical allodynia induced by paclitaxel. Electron micrographs of sciatic nerve revealed that 5-HD reduced the damages caused by paclitaxel in the nonmyelinated and smaller myelinated fibers. The mechanistic study on DRG neurons suggested that 5-HD rescued the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, 5-HD did not jeopardize the antitumor effect of paclitaxel in tumor xenograft models. In conclusion, we established an imaged-based high-content screening platform and a protocol for verifying the neuroprotective effect in vivo, by which 5-HD was identified and validated as a potential neuroprotective drug for paclitaxel-induced neuropathy.

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“…The clinical manifestations include symmetric painful paresthesia or numbness in a stocking-glove distribution, shaking, impaired proprioception, sensory ataxia, gait disturbance, and occasional weakness (Stubblefield et al, 2009). These symptoms have a variable clinical course and are resolved after treatment discontinuation (Argyriou et al, 2008). The onset dose for neuropathy of any grade ranges from 100 to 300 mg/m 2 for paclitaxel (PTX) and from 75 to 100 mg/m 2 for DOC.…”

Section: Discussionmentioning

confidence: 99%

“…It is difficult to control this side effect because the mechanisms underlying the development of neuropathy have not been clarified. The most widely accepted proposed mechanism for taxaneinduced peripheral neuropathy is that an atrophic effect starting at the distal nerve endings, followed by changes in Schwann cells, the neuronal body, or axonal transport and the downregulation of the expression of proteins and other components involved in active neuronal intracellular transport play the most significant roles in the induction of taxane-induced peripheral neuropathy (Argyriou et al, 2008). Several types of neuroprotective agent have been tested as treatments for taxane-induced neuropathy in animal and clinical models (Lee and Swain, 2006).…”

Section: Discussionmentioning

confidence: 99%

The Kampo Medicine Goshajinkigan Prevents Neuropathy in Breast Cancer Patients Treated with Docetaxel

Abe¹,

Kawai²,

Mori³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. Materials and Methods: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. Results: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7±2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9±2.4. Conclusions: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

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Peripheral nerve damage associated with administration of taxanes in patients with cancer

Cited by 216 publications

References 79 publications

Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity

Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity

Integrating Image-Based High-Content Screening with Mouse Models Identifies 5-Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy

The Kampo Medicine Goshajinkigan Prevents Neuropathy in Breast Cancer Patients Treated with Docetaxel

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