Chapter Sixteen - Chemotherapy-Induced Peripheral Neuropathy
Section snippets
Chemotherapy-Induced Neuropathy: An Introduction
With considerable advances in the development of anticancer agents over the past 20–30 years, patients diagnosed with cancer are surviving and living longer following treatment.1 With this increase in survival, researchers and patients are now shifting their focus toward a primary side effect of anticancer treatment, chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is an adverse effect following treatment with multiple classes of chemotherapeutics, including platinum
Microtubule-targeting agents
Alterations in microtubule dynamics are a common mechanism of blocking mitosis within dividing cells, which lead to subsequent apoptosis in cancer cells,31 and MTAs have been developed and used extensively as anticancer drugs.32 There are two main classes of MTAs, which are compounds that bind directly to the tubulin subunits to alter the dynamic rearrangement of microtubules. Compounds that bind free β-tubulin subunits and prevent polymerization into microtubules are called depolymerizing or
Clinical Assessment of CIPN
A limitation to the interpretation of some clinical studies is the subjective nature by which the presence and intensity of neuropathy is determined by the clinicians and patients. There is much debate regarding the proper endpoints to use to determine the severity of neuropathy in patients and the intensity of neuropathy is often difficult to gage. Several grading scales have been developed by the World Health Organization, Eastern Cooperative Oncology Group, and the National Cancer Institute
Experimental Studies: Animal Models of CIPN
Experimental animal models have been developed to examine the mechanisms of CIPN following exposure to paclitaxel, vincristine, epothilones, cisplatin, oxaliplatin, bortezomib, or thalidomide. Although these animal models have evolved over time to closely mimic the behavioral and neurophysical symptoms observed in patients receiving chemotherapy, the initial animal studies were performed using high doses of the chemotherapeutic drugs. These high doses of drugs caused sensory neuron death, overt
Experimental Studies: In Vitro Models of CIPN
To accurately delineate the intracellular signaling mechanisms by which chemotherapeutics alter the sensitivity of sensory neurons, investigators have broadened their research to include in vitro models of CIPN. Cultures of sensory neurons provide a tightly controlled system which allows relatively easy manipulation of protein expression and function via genetic and pharmacological tools. The limitation of neuronal cultures is that the neurons have been removed from their native environment and
Proposed Mechanisms Underlying CIPN
There have been multiple theories on the mechanisms by which each of the chemotherapeutics alters neuronal function. In this section, the use of pharmacological interventions that have been used for other types of neuropathic pain will be discussed. In addition, various putative mechanisms will be discussed in the context of the clinical and experimental evidence supporting or refuting that mechanism. It is appreciated that many of these proposed mechanisms may overlap, and thus, it is probable
Challenges to CIPN Research
There has been very little success in translating preclinical findings to efficacious therapies for patients suffering with CIPN. One caveat that has been largely unaddressed in CIPN research is the possibility that the presence of cancer may predispose patients to neuropathy or induce novel interactions with anticancer drugs to “prime” patients to develop a more robust neuropathy than that which is observed in preclinical models. The presence of cancer alone has been shown to induce central
References (294)
- et al.
Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies
Eur J Cancer
(2008) - et al.
Paclitaxel-induced neuropathy
Ann Oncol
(1995) - et al.
Characterization of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel
Neuroscience
(2012) - et al.
Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients
Pain
(2004) - et al.
Late non-neoplastic events in patients with aggressive non-Hodgkin’s lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials
Clin Lymphoma Myeloma
(2005) - et al.
Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer
Ann Oncol
(2002) - et al.
Incapacitating autonomic neuropathy precipitated by taxol
Gynecol Oncol
(1993) - et al.
Chemotherapy-induced neuropathy: a comprehensive survey
Cancer Treat Rev
(2014) - et al.
Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer
Eur J Cancer Clin Oncol
(1988) - et al.
Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma
Ann Oncol
(1990)
NICE guidance on bortezomib and thalidomide for first-line treatment of multiple myeloma
Lancet Oncol
Quantitative sensory findings in patients with bortezomib-induced pain
J Pain
Fibroblast growth factor signaling in tumorigenesis
Cytokine Growth Factor Rev
Peripheral neuropathy with microtubule-targeting agents: occurrence and management approach
Clin Breast Cancer
Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: a clinical and electrophysiologic study
Clin Oncol (R Coll Radiol)
Structural and functional differences between neuropathy with and without pain?
Exp Neurol
Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis
Clin Neurophysiol
Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol
Exp Neurol
Chronic pain in the cancer survivor: a new frontier
Pain Med
Reversible peripheral neuropathy induced by a single administration of high-dose paclitaxel
Neurology
Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine
Cancer Chemother Pharmacol
Oxaliplatin-induced neurotoxicity and the development of neuropathy
Muscle Nerve
Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity
J Clin Oncol
Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing
J Neurooncol
Taxol produces a predominantly sensory neuropathy
Neurology
Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy
Muscle Nerve
Taxol impairs anterograde axonal transport of microinjected horseradish peroxidase in dorsal root ganglia neurons in vitro
Cell Tissue Res
Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats
Acta Neuropathol
Neurotoxicity of Taxol
J Natl Cancer Inst Monogr
Phase I clinical and pharmacokinetic study of taxol
Cancer Res
Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer
J Clin Oncol
Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies
Cancer
Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies
Ann Neurol
Peripheral neuropathy induced by microtubule-stabilizing agents
J Clin Oncol
Chemotherapy-induced neuropathy
J Peripher Nerv Syst
Sequences of taxol and cisplatin: a phase I and pharmacologic study
J Clin Oncol
Cisplatin-induced peripheral neuropathy. Frequent off-therapy deterioration, demyelinating syndromes, and muscle cramps
Cancer
Cisplatin neurotoxicity in the treatment of metastatic germ cell tumour: time course and prognosis
Br J Cancer
Observational study of prevalence of long-term Raynaud-like phenomena and neurological side effects in testicular cancer survivors
J Natl Cancer Inst
Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility
Oncologist
Full dose vincristine (without 2-mg dose limit) in the treatment of lymphomas
Cancer
Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia
J Peripher Nerv Syst
Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death
Cancer Res
New microtubule/tubulin-targeted anticancer drugs and novel chemotherapeutic strategies
J Chemother
The vinca alkaloids: a new class of oncolytic agents
Cancer Res
Cancer chemotherapy
Annu Rev Pharmacol
Preclinical and clinical pharmacology of vinca alkaloids
Drugs
Epothilones: a novel class of non-taxane microtubule-stabilizing agents
Curr Pharm Des
Taxanes and other microtubule stabilizing agents
Cancer Chemother Biol Response Modif
The paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism
Cancer J
Cited by (59)
A Serum-Stable supramolecular drug carrier for chemotherapeutics fabricated by a Peptide-Photosensitizer conjugate
2023, Journal of Colloid and Interface ScienceCalcium signaling in chemotherapy-induced neuropathy
2023, Cell CalciumRole of tubulin post-translational modifications in peripheral neuropathy
2023, Experimental NeurologyCitation Excerpt :CIPN is characterized by loss of peripheral nerve function and typically manifests with a distal-to-proximal pattern of progressive peripheral sensory nerve loss. Several different classes of anticancer drugs possessing diverse antineoplastic mechanisms induce CIPN (Cavaletti et al., 2008; Fehrenbacher, 2015; Ferrier et al., 2013). However, sensory impairment is either the only or the predominant adverse effect of these agents, suggesting the existence of a common mechanism of pathogenesis (Cavaletti and Marmiroli, 2010).
Effects of foam pad balance exercises on cancer patients undergoing chemotherapy: A randomized control trial
2021, Journal of Bodywork and Movement TherapiesCitation Excerpt :Chemotherapy has a neurotoxic effect that may damage the peripheral nervous system and can spread to dorsal root ganglia unprotected by the blood-brain barrier (Carozzi et al., 2015). Chemotherapy patients usually suffer from CIPN symptoms, such as numbness, tendon reflex loss, and subsequent loss of balance and physical performance (Fehrenbacher, 2015; Schmitz et al., 2010). The prevalence of CIPN was reported to be approximately 60 % at 3 months and 30 % at 6 months after chemotherapy (Seretny et al., 2014).