Early predictors of peripheral neurotoxicity in cisplatin and paclitaxel combination chemotherapy

Università degli Studi di Milano-Bicocca, Milano, Lombardy, Italy
Annals of Oncology (Impact Factor: 7.04). 09/2004; 15(9):1439-42. DOI: 10.1093/annonc/mdh348
Source: PubMed


We investigated the possible use of clinical signs of chemotherapy-induced peripheral neurotoxicity (CIPN) or of nerve growth factor (NGF) circulating levels to predict the final outcome of CIPN.
Sixty-two women affected by locally advanced squamous cervical carcinoma treated with TP (paclitaxel 175 mg/m2 over a 3 h infusion plus cisplatin 75 mg/m2) or TIP (TP plus ifosphamide 5 mg/m2) were examined and scored according to the Total Neuropathy Score (TNS), before and during chemotherapy.
A correlation with the final severity of CIPN was observed with vibration perception and deep tendon reflex evaluation, while pin sensibility, strength, and autonomic symptoms and signs were not informative. A highly significant correlation existed between the decrease in circulating levels of NGF and the severity of CIPN (r = -0.579; P < 0.001; 95% confidence limits -0.702 to -0.423). However, circulating levels of NGF were not effective as predictors of the final neurological outcome of each patient.
Our study indicates that a precise clinical evaluation of the peripheral nervous system of patients treated with platinum and taxane combination polychemotherapy not only gives reliable information regarding the course of CIPN, but also can be used to predict the final neurological outcome of the treatment.

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Available from: Claudio Zanna, Mar 15, 2014
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    • "Previous evidence indicates that a precise clinical evaluation combined with detailed electrophysiological testing could predict the final neurological outcome of CIPN (Cavaletti et al., 2004; Argyriou et al., 2005). "
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    ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI-PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and class 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95%CI: 1.28-6.07), 3.49 (95%CI: 1.61-7.55) and 4.42 (95%CI: 1.35-14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and class 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81-41.42), 2.54 (95%CI: 1.19-5.41) and 7.47 (95%CI: 2.49-22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN.
    Full-text · Article · May 2014 · Journal of the Peripheral Nervous System
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    • "Neuronal damage by antineoplastic agents probably activates second messenger systems which cause hyperalgesia, allodynia, and pain, because it may be relieved by supplementation with trophic factors such as NGF, insulin growth factor 1 (IGF-1), and neurotrophin 3 (NT-3) [40]. There is a large experimental evidence base on the involvement of NGF in CIPN [41] [42] [43] [44]. NGF promotes physiological maturation, survival, and expression of the specific phenotype in primary sensory neurons located in the DRG [45]. "
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    ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment.
    Full-text · Article · Jul 2013 · Evidence-based Complementary and Alternative Medicine
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    • "NGF has been demonstrated to counteract the reduction of neurite outgrowth from rat DRG in vitro, induced by cisplatin, vincristine or Taxol [96] and the development of behavioral manifestations of cisplatin-induced neuropathy [69,97-101]. Moreover, a positive correlation was found between the decrease of circulating NGF and the severity of CIPN in humans [102]. "
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    ABSTRACT: The physiological role of the neurotrophin nerve growth factor (NGF) has been characterized, since its discovery in the 1950s, first in the sensory and autonomic nervous system, then in central nervous, endocrine and immune systems. NGF plays its trophic role both during development and in adulthood, ensuring the maintenance of phenotypic and functional characteristic of several populations of neurons as well as immune cells. From a translational standpoint, the action of NGF on cholinergic neurons of the basal forebrain and on sensory neurons in dorsal root ganglia first gained researcher's attention, in view of possible clinical use in Alzheimer's disease patients and in peripheral neuropathies respectively. The translational and clinical research on NGF have, since then, enlarged the spectrum of diseases that could benefit from NGF treatment, at the same time highlighting possible limitations in the use of the neurotrophin as a drug. In this review we give a comprehensive account for almost all of the clinical trials attempted until now by using NGF. A perspective on future development for translational research on NGF is also discussed, in view of recent proposals for innovative delivery strategies and/or for additional pathologies to be treated, such as ocular and skin diseases, gliomas, traumatic brain injuries, vascular and immune diseases.
    Full-text · Article · Nov 2012 · Journal of Translational Medicine
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