Can pregabalin prevent paclitaxel-associated neuropathy?—An ACCRU pilot trial

Shinde, Shivani; Seisler, Drew K.; Soori, Gamini S.; Atherton, Philip J.; Pachman, Deirdre R.; Lafky, Jacqueline M.; Ruddy, Kathryn J.; Loprinzi, Charles L.

doi:10.1007/s00520-015-2807-5

Cited by 54 publications

(26 citation statements)

References 24 publications

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“…Nevertheless, 15 patients (25%) recovered between 2 and 6 months, and nine patients (15%) after 6 months and more. Regarding a 46-patient cohort (ACCRU pilot trial) treated with paclitaxel alone, similar results were reported based on the sensory neuropathy scores of the QLQ-CIPN20 of the EORTC ( Shinde et al, 2016 ). In a study conducted in the Netherlands, most of the patients complained about neurotoxicity in the upper and lower extremities 6 months after cessation of chemotherapy with oxaliplatin, paclitaxel, or docetaxel (78.8 and 89.7%, respectively) ( Beijers A. et al, 2014 ).…”

Section: Taxanessupporting

confidence: 68%

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

et al. 2017

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Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the case of bortezomib and thalidomide-induced peripheral neuropathy.

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Section: Taxanessupporting

confidence: 68%

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

et al. 2017

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“…Paclitaxel-induced neuropathic pain (PINP) is characterized by numbness, tingling, and ongoing burning pain in the glove and stocking areas of the hands and feet [ 5 , 6 ]. Unfortunately, PINP is refractory to commonly used analgesic strategies, such as nonsteroidal anti-inflammatory drugs, antiepileptics, and antidepressants [ 7 – 9 ]. To date, no effective treatment is available to prevent or alleviate PINP due to the poor understanding of its mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain

et al. 2020

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Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 activator, oltipraz (10, 50, and 100 mg/kg), dose-dependently attenuated established mechanical allodynia, whereas repeated injection of oltipraz (100 mg· kg −1 · d −1 , i.p. from d 14 to d 18) almost abolished the mechanical allodynia in PINP rats. The antinociceptive effect of oltipraz was blocked by pre-injection of Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg −1 · d −1 , i.p. from d 0 to d 6) failed to prevent the development of the PINP, but delayed its onset. Western blot and immunofluorescence analysis revealed that the expression levels of Nrf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats. Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.

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“…Other RCTs evaluating the efficacy of recombinant human leukemia inhibitory factor (AM424), acetyl‐l‐carnitine, pregabalin, omega‐3, retinoic acid, minocycline, lafudine, and vitamin B complexes failed to demonstrate the efficacy of these agents in preventing neurotoxicity caused by paclitaxel‐based chemotherapeutic regimens …”

Section: Introductionmentioning

confidence: 99%

Taxane and epothilone‐induced peripheral neurotoxicity: From pathogenesis to treatment

Tamburin

Park

Alberti

et al. 2019

J Peripheral Nervous Sys

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Taxane-induced peripheral neurotoxicity (TIPN) is the most common nonhematological side effect of taxane-based chemotherapy, and may result in dose reductions and discontinuations, having as such a detrimental effect on patients' overall survival. Epothilones share similar mechanism of action with taxanes. The typical TIPN clinical presentation is mainly comprised of numbness and paresthesia, in a stocking-and-glove distribution and may progress more proximally over time, with paclitaxel being more neurotoxic than docetaxel. Motor and autonomic involvement is less common, whereas an acute taxane-induced acute pain syndrome is frequent. Patient reported outcomes questionnaires, clinical evaluation, and instrumental tools offer complementary information in TIPN. Its electrodiagnostic features include reduced/abolished sensory action potentials, and less prominent motor involvement, in keeping with a length-dependent, axonal dying back predominately sensory neuropathy. TIPN is dose-dependent and may be reversible within months after the end of chemotherapy. The single and cumulative delivered dose of taxanes is considered the main risk factor of TIPN development. Apart from the cumulative dose, other risk factors for TIPN include demographic, clinical, and pharmacogenetic features with several single-nucleotide polymorphisms potentially linked with increased susceptibility of TIPN. There are currently no neuroprotective strategies to reduce the risk of TIPN, and symptomatic treatments are very limited. This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of TIPN. K E Y W O R D S assessment, chemotherapy, docetaxel, ixabepilone, neurotoxicity, paclitaxel, prevention 1 | INTRODUCTION Taxanes (paclitaxel, docetaxel, cabazitaxel) were among the most important new chemotherapy agents in the late 20th century. 1 Paclitaxel is a natural compound with potent anticancer properties, which was originally isolated from the bark of the Pacific yew tree (Taxus brevifolia) in 1967, but low natural availability and insolubility in water hindered its diffusion since the 1980s. 2 Paclitaxel and docetaxel are currently obtained through a semisynthetic process from a precursor contained in the needles of the European yew tree (Taxus baccata),which is more widely available worldwide. 2 Nanoparticle albuminbound paclitaxel (nab-paclitaxel) is a novel formulation containing human serum albumin to encapsulate hydrophobic paclitaxel molecules to increase tumor uptake and reduce hypersensitivity

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Can pregabalin prevent paclitaxel-associated neuropathy?—An ACCRU pilot trial

Abstract: The results of this pilot trial do not support that pregabalin is helpful for preventing P-APS or paclitaxel-associated CIPN.

Cited by 54 publications

References 24 publications

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain

Taxane and epothilone‐induced peripheral neurotoxicity: From pathogenesis to treatment

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