Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?
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ABSTRACT:
SUBMITTER: Cavaletti G
PROVIDER: S-EPMC8804126 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In view of advances in early detection and treatment, the 5-year relative survival rate for all cancer patients combined is now approximately 66%. As a result, there are more than 13.7 million cancer survivors in the United States, with this number increasing by 2% annually. For many patients, improvements in survival have been countered by therapy-associated adverse effects that may seriously impair long-term functional status, workplace productivity, and quality of life. Approximately 20% to 40% of cancer patients given neurotoxic chemotherapy develop chemotherapy-induced peripheral neurotoxicity (CIPN), which represents one of the most common and potentially permanent nonhematologic side effects of chemotherapy. Permanent bilateral hearing loss and/or tinnitus can result from several ototoxic therapies, including cisplatin- or carboplatin-based chemotherapy. CIPN and ototoxicity represent important challenges because of the lack of means for effective prevention, mitigation, or a priori identification of high-risk patients, and few studies have applied modern genomic approaches to understand underlying mechanisms/pathways. Translational genomics, including cell-based models, now offer opportunities to make inroads for the first time to develop preventive and interventional strategies for CIPN, ototoxicity, and other treatment-related complications. This commentary provides current perspective on a successful research strategy, with a focus on cisplatin, developed by an experienced, transdisciplinary group of researchers and clinicians, representing pharmacogenomics, statistical genetics, neurology, hearing science, medical oncology, epidemiology, and cancer survivorship. Principles outlined herein are applicable to the construction of research programs in translational genomics with strong clinical relevance and highlight unprecedented opportunities to understand, prevent, and treat long-term treatment-related morbidities.
| S-EPMC4568989 | biostudies-literature
Project description:PurposeSleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality.MethodsParticipants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors.ResultsAmong 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05).ConclusionsParticipants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.
| S-EPMC10733204 | biostudies-literature
Project description:In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the published literature concerning the evaluation of assessment measures for paediatric chemotherapy-induced peripheral neurotoxicity. We searched PubMed, CINAHL, PsycINFO, and Embase on Nov 7-8, 2018; of 1409 articles, seven met the inclusion criteria. A total of 335 children (excluding ten healthy controls) were enrolled in the seven studies and the sample sizes ranged from 17 to 86 individuals. 276 (82%) of the 335 children were actively undergoing chemotherapy treatment. Most studies did not comprehensively evaluate the psychometric properties of assessment measures for chemotherapy-induced peripheral neurotoxicity. By use of a narrative analysis that combined approaches from the Joanna Briggs Institute (Adelaide, SA, Australia) and the quality of diagnostic accuracy studies assessment method (known as QUADAS), only one study was deemed high quality. We identified two variants of the Total Neuropathy Score, two grading scales, two semi-objective tests, one patient-reported outcome, and several mobility measures. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Balis grading scales showed lower sensitivity and specificity than the items of the Total Neuropathy Score. Although there is insufficient evidence to support the use of most approaches to assess chemotherapy-induced peripheral neurotoxicity in children, two variants of the Total Neuropathy Score, the pediatric-modified Total Neuropathy Score and the Total Neuropathy Score-pediatric vincristine, are promising but require further testing. Other approaches are less sensitive or less feasible. A patient-reported outcome measure for chemotherapy-induced peripheral neurotoxicity in children is needed.
| S-EPMC8152573 | biostudies-literature
Project description:BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is regarded as one of the most common dose-limiting adverse effects of several chemotherapeutic agents, such as platinum derivatives (oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib. CIPN affects more than 60% of patients receiving anticancer therapy and although it is a nonfatal condition, it significantly worsens patients' quality of life. The number of analgesic drugs used to relieve pain symptoms in CIPN is very limited and their efficacy in CIPN is significantly lower than that observed in other neuropathic pain types. Importantly, there are currently no recommended options for effective prevention of CIPN, and strong evidence for the utility and clinical efficacy of some previously tested preventive therapies is still limited.MethodsThe present article is the second one in the two-part series of review articles focused on CIPN. It summarizes the most recent advances in the field of studies on CIPN caused by oxaliplatin, the third-generation platinum-based antitumor drug used to treat colorectal cancer. Pharmacological properties of oxaliplatin, genetic, molecular and clinical features of oxaliplatin-induced neuropathy are discussed.ResultsAvailable therapies, as well as results from clinical trials assessing drug candidates for the prevention of oxaliplatin-induced neuropathy are summarized.ConclusionEmerging novel chemical structures-potential future preventative pharmacotherapies for CIPN caused by oxaliplatin are reported.
| S-EPMC7329798 | biostudies-literature
Project description:Background and objectiveThere is no agreement on the gold standard for detection and grading of chemotherapy-induced peripheral neurotoxicity (CIPN) in clinical trials. The objective is to perform an observational prospective study to assess and compare patient-based and physician-based methods for detection and grading of CIPN.MethodsConsecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy, were enrolled in the United States, European Union, or Australia. A trained investigator performed physician-based scales (Total Neuropathy Score-clinical [TNSc], used to calculate Total Neuropathy Score-nurse [TNSn]) and supervised the patient-completed questionnaire (Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX]). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline, we assessed the association between TNSc, TNSn, and FACT/GOG-NTX. Considering a previously established minimal clinically important difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the 2 groups.ResultsData from 254 participants were available: 180 (71%) had normal neurologic status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn, and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen, we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r = 0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.7 for TNSc and 2.8 for the TNSn.ConclusionsMCID for TNSc and TNSn were calculated and the TNSn can be considered a reliable alternative objective clinical assessment if a more extended neurologic examination is not possible. The FACT/GOG-NTX score can be reduced to 7 items and these items correlate well with the TNSc and TNSn.Classification of evidenceThis study provides Class III evidence that a patient-completed questionnaire and nurse-assessed scale correlate with a physician-assessed scale.
| S-EPMC10365895 | biostudies-literature
Project description:Peripheral neurotoxicity is a disturbing issue for cancer patients who are treated with chemotherapy. Several medications have been developed for preventing chemotherapy-induced chronic neurotoxicity (CICNT) however; their relative efficacies have not yet been studied. In this study, we conducted a network meta-analysis to give intervention recommendations. The literature was searched in a variety of databases and eligible studies were chosen based on predefined criteria. Data extraction and statistical analysis was performed, and the results are displayed using the odds ratio (OR) and corresponding 95% credible intervals (CrI) with respect to overall and severe neurotoxicity. The medications were ranked according to their surface under cumulative ranking curve values. The consistency of direct and indirect evidence was also evaluated. We found that patients with amifostine or vitamin E (VE) treatment exhibited a lower risk of overall neurotoxicity compared to those using the placebo (amifostine: OR = 0.10, 95% CrI: 0.02-0.46; VE: OR = 0.08, 95% CrI: 0.01-0.99). In regard to preventing severe neurotoxicity, glutathione and amifostine treatment appeared to be significantly more effective than the placebo (glutathione: OR = 0.19, 95% CrI: 0.04-0.64; amifostine: OR = 0.12, 95% CrI: 0.02-0.48). In summary, amifostine, VE, and glutathione treatment is considered to be effective in lowering the risk of CICNT. However, further studies which consider safety are required.
| S-EPMC5462987 | biostudies-literature
Project description:PurposeThe Patient Neurotoxicity Questionnaire (PNQ) represents a diagnostic tool concerning patients with chemotherapy-induced peripheral neuropathy (CIPN). The application of such a tool in the Greek clinical praxis requires validation.MethodsValidation consists of three stages - translation, reverse translation, and patient application. Hundred oncologic patients were assessed by comparing the PNQ to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) at the chemotherapy onset and second, fourth, and sixth sessions. The diagnostic tool's specific requirements (compliance, validity, concordance, sensitivity, specificity, reliability) were statistically evaluated.ResultsDifferences between translated texts and between the reverse translation and the original were considered negligible. At the second, fourth, and sixth session compliance was 98%, 95%, and 93% while Cronbach's α was 0,57 0,69, and 0,81, respectively. Cohen's weighted κ was 0,67 and 0,58, Spearman's ρ was 0,7 and 0,98, while the area under the curve (AUC) of the receiver operating characteristic (ROC) was 1 and 0,9 for the sensory and the motor part, respectively. The variance's linear regression analysis confirmed CIPN worsening over time (P<0.0001).DiscussionThe Greek version remains close to the original English version. Compliance rates reflect easy PNQ applications. Cohen's κ values highlight the physicians' tension to underestimate the patients' condition. Spearman's ρ, Cronbach's α, and AUC values reflect good validity, reliability, and specificity of the PNQ respectively. Finally, the linear analysis confirmed the PNQ sensitivity over time.ConclusionsThe PNQ validation in Greek adds a crucial tool to the physicians' armamentarium. It can now delineate the necessary information to modify the chemotherapy and analgesic treatment regimens at both preventive and acute levels.
| S-EPMC8025796 | biostudies-literature
Project description:BackgroundChemotherapy-induced peripheral neurotoxicity (CIPN) is the most common adverse effect in patients undergoing chemotherapy, and no effective interventions are currently available for its prevention and treatment. Non-pharmacological therapies appear to be beneficial for the prevention and treatment of CIPN, but it remains unclear which therapy is most effective. The aim of this study was to identify the most effective non-pharmacological therapy for CIPN patients.MethodsPubMed, Web of Science, Embase, and Cochrane Library were searched for randomized controlled trials on non-pharmacological therapies for CIPN. The primary outcomes included pain and peripheral neuropathological symptoms, and the secondary outcomes included quality of life, sensory and motor symptoms. The pairwise analysis and a network meta-analysis were performed using a random effects model.ResultsA total of 46 articles were included in this study, involving 2,878 participants. Our study showed that massage was more effective in pain-alleviating compared with acupuncture [SMD = 0.81, 95%CI (0.04, 1.57)], vitamin and gabapentin [SMD = 2.56, 95%CI (1.39, 3.74)], and usual care and placebo [SMD = 0.9, 95%CI (0.31, 1.49)]. As for attenuating peripheral neuropathological symptoms, massage was more effective than usual care and placebo [SMD = 0.75, 95%CI (0.33, 1.17)], sensorimotor training [SMD = 1.17, 95%CI (0.24, 2.10)], electrostimulation [SMD=-1.18, 95%CI (-2.14, -0.21)], multimodal exercise [SMD=-0.82, 95%CI (-1.57, -0.08)], and resistance training [SMD = 1.03, 95%CI (0.11, 1.95)]. Massage was also more effective than other non-pharmacological therapies in improving quality of life, sensory and motor symptoms.ConclusionsAccording to our study, massage has advantages in alleviating pain, improving quality of life, and improving peripheral neuropathological symptoms and has better effect than other non-pharmacological interventions, representing certain clinical significance. However, the results of this study should be interpreted with caution due to the limitations of the included studies. In the future, more high-quality multi arm randomized controlled trials can be attempted to provide direct comparisons of the relative effects of non-pharmacological interventions.
| S-EPMC10712106 | biostudies-literature
Project description:Background and purposeA real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN.MethodsThis single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2.ResultsEighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001).ConclusionsA variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.
| S-EPMC11295167 | biostudies-literature
Project description:Chemotherapy-induced peripheral neuropathy is a frequent treatment-limiting factor that significantly impairs patients' everyday life, also because of a lack of valid palliative options. Here, we report a case of a male patient with a history of metastatic colon cancer and previous chemotherapies. He came to our attention with a peripheral neuropathy that impaired his quality of life and could limit the further line of chemotherapy. We treated the neuropathy with menthol aqueous cream with benefit.
| S-EPMC5545968 | biostudies-other