Taxol produces a predominantly sensory neuropathy

Lipton, Richard B.; Apfel, Stuart C.; Dutcher, Janice P.; Rosenberg, Richard F.; Kaplan, Jonathan; Berger, Alan R.; Einzig, Avi I.; Wiernik, Peter H.; Schaumburg, Herbert H.

doi:10.1212/wnl.39.3.368

Cited by 283 publications

(133 citation statements)

References 0 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…Intermediate concentrations of paclitaxel were present in the sciatic nerve and spinal cord, possibly due to paclitaxel transport along the centrifugal and centripetal branches of the dorsal root ganglia neuron axons [9]. Paclitaxel induced neuropathy is probably due to dysfunctional microtubules in dorsal root ganglia, axons and Schwann cells [10,11]. In vivo studies have shown that direct injection of paclitaxel into the rat sciatic nerve causes the formation of unusual microtubule aggregates resulting in demyelination and loss of axoplasmic transport [10,11].…”

Section: Pathogenesis Of Paclitaxel-mediated Neuropathymentioning

confidence: 99%

“…Paclitaxel induced neuropathy is probably due to dysfunctional microtubules in dorsal root ganglia, axons and Schwann cells [10,11]. In vivo studies have shown that direct injection of paclitaxel into the rat sciatic nerve causes the formation of unusual microtubule aggregates resulting in demyelination and loss of axoplasmic transport [10,11].…”

Section: Pathogenesis Of Paclitaxel-mediated Neuropathymentioning

confidence: 99%

“…The neurotoxicity is dose-and infusion-duration related, and most frequently occurs when the dose of paclitaxel per administration exceeds 250 mg/m 2 infused over 24 hours [10,12,22]. Early on, infusion related reactions and neutropenia were the most common adverse effects seen with the use of paclitaxel.…”

Section: Clinical Paclitaxel-mediated Neurotoxi-citymentioning

confidence: 99%

See 2 more Smart Citations

Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives

Scripture

Figg²,

Sparreboom³

2006

266

181

View full text Add to dashboard Cite

Abstract:Paclitaxel is an antineoplastic agent derived from the bark of the western yew, Taxus brevifolia, with a broad spectrum of activity. Because paclitaxel promotes microtubule assembly, neurotoxicity is one of its side effects. Clinical use of paclitaxel has led to peripheral neuropathy and this has been demonstrated to be dependent upon the dose administered, the duration of the infusion, and the schedule of administration. Vehicles in the drug formulation, for example Cremophor in Taxol ® , have been investigated for their potential to induce peripheral neuropathy. A variety of neuroprotective agents have been tested in animal and clinical studies to prevent paclitaxel neurotoxicity. Recently, novel paclitaxel formulations have been developed to minimize toxicities. This review focuses on recent advances in the etiology of paclitaxel-mediated peripheral neurotoxicity, and discusses current and ongoing strategies for amelioration of this side effect.

show abstract

Section: Pathogenesis Of Paclitaxel-mediated Neuropathymentioning

confidence: 99%

Section: Pathogenesis Of Paclitaxel-mediated Neuropathymentioning

confidence: 99%

See 1 more Smart Citation

Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives

Scripture

Figg²,

Sparreboom³

2006

266

181

View full text Add to dashboard Cite

show abstract

“…4,5 On the other hand, neurotoxicity cannot be prevented nor treated, can last for months, and in severe cases it may cause irreversible nerve damage. 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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

View full text Add to dashboard Cite

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.

show abstract

“…An important dose-dependent side-effect of cisplatin is the development of peripheral neuropathy, mainly affecting thick-fibre-mediated sensory qualities (Thompson et al, 1984;Roelofs et al, 1984;Gerritsen van der Hoop et al, 1990a;Vecht et al, 1991; Hilkens et al, 1994). Neuropathy has also been reported as a dose-dependent side-effect of treatment with paclitaxel (Taxol) (Lipton et al, 1989;Gerven et al, 1994). As expected, trials on combination chemotherapy of cisplatin and paclitaxel found a high incidence of peripheral neuropathy (Rowinsky et al, 1991;Rowinsky et al, 1993;Chaudhry et al, 1994).…”

mentioning

confidence: 99%

Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin

Hilkens

Pronk²,

Verweij³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin PHE Hilkens1, LC Pronk2, J Verweij2, CJ Vecht1, WLJ van Putten3 and MJ van den Bent1Departments of 2Medical Oncology and 3Biostatistics, Dr Daniel den Hoed Cancer Center and University Hospital, Rotterdam, The Netherlands Summary Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel -cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m-2, 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses.Keywords: neuropathy; docetaxel; cisplatin; neurotoxicity; peripheral nerves; chemotherapy Docetaxel (Taxotere) is a new semisynthetic taxoid that has demonstrated substantial clinical activity against a wide variety of solid tumours (Pazdur et al, 1993;Aamdal et al, 1994;Fossella et al, 1994;Francis et al, 1994a;Francis et al, 1994b;Smyth et al, 1994;Chevallier et al, 1995). Docetaxel inhibits tubulin depolymerization and promotes microtubule assembly, resulting in dysfunctional microtubules (Pazdur et al, 1993).In view of their partly non-overlapping side-effects and their activities in a wide range of tumour types, developing combination chemotherapy regimens, including both taxoids and platins, is of major interest (Rowinsky et al, 1991;Rowinsky et al, 1993;Chaudhry et al, 1994). An important dose-dependent side-effect of cisplatin is the development of peripheral neuropathy, mainly affecting thick-fibre-mediated sensory qualities (Thompson et al, 1984;Roelofs et al, 1984;Gerritsen van der Hoop et al, 1990a;Vecht et al, 1991; Hilkens et al, 1994). Neuropathy has also been reported as a dose-dependent side-effect of treatment with paclitaxel (Taxol) (Lipton et al, 1989;Gerven et al, 1994). As expected, trials on combination chemotherapy of cisplatin and paclitaxel found a high incidence of peripheral neuropathy (Rowinsky et al, 1991;Rowinsky et al, 1993;Chaudhry et al, 1994).Peripheral neurotoxicity has been reported as a frequent, but usually mild side-effect of docetaxel in several phase I and phase II studie...

show abstract

Taxol produces a predominantly sensory neuropathy

Cited by 283 publications

References 0 publications

Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives

Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives

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

Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin

Contact Info

Product

Resources

About