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Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

ABSTRACT: Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.

SUBMITTER: Cavaletti G

PROVIDER: S-EPMC8804126 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Cavaletti Guido G Marmiroli Paola P Renn Cynthia L CL Dorsey Susan G SG Serra Maria Pina MP Quartu Marina M Meregalli Cristina C

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20211019 4

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacologica ...[more]

PMID: 34668147

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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.

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.

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.

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Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Publications

Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

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