Chemotherapy neurotoxicity

BACKGROUND: Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study was aimed to develop and evaluate Normal-Tissue Complication Probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year and 2-year Neurocognitive Decline (ND) post-radiotherapy. METHODS: A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included...

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection...

BACKGROUND: Survivors of pediatric acute lymphoblastic leukemia (ALL) exhibit abnormal neurocognitive outcomes that are possibly due to exposures to neurotoxic chemotherapy agents. This study aimed to determine the feasibility of characterizing long-term neuroanatomical changes with in vivo neuroimaging in a preclinical model of treatment for ALL. METHODS: Female mice (C57BL/6) were randomly assigned to a saline control group (n=10) or a treatment group (n=10) that received intrathecal methotrexate and oral dexamethasone (IT-MTX + DEX)...

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy...

Pancreatic adenocarcinoma (PDAC) is highly resistant to conventional chemotherapeutic interventions, resulting in exceptionally low survival rates. The limited efficacy can in part be attributed to dose limitations and treatment cessation urged by toxicity of currently used chemotherapy. The advent of targeted delivery strategies has kindled hope for circumventing off-target toxicity. We have previously reported a PDAC-specific mesoporous silica nanoparticle (MSN) containing a protease linker responsive to ADAM9, a PDAC-enriched extracellularly deposited protease...

BACKGROUND: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain and is a non-proteinogenic amino acid. Doxorubcin (DOX) or adriamycin is one of the most potent chemotherapy drugs for breast cancer. PURPOSE: This study focused on diminishing the brain injury and neurotoxicity of doxorubicin (DOX) by GABA administration. METHODS: Rats were randomly divided into four groups (8 rats each), which were the control group, DOX group (3 mg/kg for 4 weeks, then 2 mg/kg for 2 weeks), GABA group (2 mg/kg for 21 days), and DOX + GABA group (treated as the second and third groups)...

Chemotherapy causes undesirable long-term neurological sequelae, chemotherapy-induced cognitive impairment (CICI), or chemobrain in cancer survivors. Activation of programmed cell death (PCD) has been proposed to implicate in the development and progression of chemobrain. Neuronal apoptosis has been extensively recognized in experimental models of chemobrain, but little is known about alternative forms of PCD in response to chemotherapy. Activation of acetylcholine receptors (AChRs) is emerging as a promising target in attenuating a wide variety of the neuronal death associated with neurodegeneration...

INTRODUCTION: Capecitabine has rarely been associated with neurotoxicity. Cerebellar ataxia, multifocal leukoencephalopathy, and sensorimotor peripheral neuropathy have been reported in the literature. A case of 6th nerve palsy associated with capecitabine has also been described. This article reports the first case of capecitabine-related 4th nerve palsy. CASE PRESENTATION: A 72-year-old Caucasian woman was referred by the Oncology Department because she had been complaining of binocular diplopia for 6 months...

The physical and functional interaction between transient receptor potential channel ankyrin 1 (TRPA1) and neuronal calcium sensor 1 (NCS-1) was assessed. NCS-1 is a calcium (Ca2+ ) sensor found in many tissues, primarily neurons, and TRPA1 is a Ca2+ channel involved not only in thermal and pain sensation but also in conditions such as cancer and chemotherapy-induced peripheral neuropathy, in which NCS-1 is also a regulatory component.We explored the interactions between these two proteins by employing western blot, qRT-PCR, co-immunoprecipitation, Ca2+ transient monitoring with Fura-2 spectrophotometry, and electrophysiology assays in breast cancer cells (MDA-MB-231) with different levels of NCS-1 expression and neuroblastoma cells (SH-SY5Y)...

Purpose. Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods. Nineteen patients (65±11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking and resistance training) or active control (nutrition education)...

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. It has been shown that CIPN can contribute to impaired quality of life (QOL) in cancer survivors. Herein, we aimed to evaluate CIPN in association with QOL in GCT survivors. PATIENTS AND METHODS: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) and Quality of Life Questionnaire (QLQ-C30) were prospectively completed by GCT survivors (N = 151) at National Cancer Institute in Slovakia during their annual follow-up...

BACKGROUND: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma. METHODS: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here...

BACKGROUND AND OBJECTIVES: The association between orofacial neurotoxicity and chemotherapy treatment is still unclear. In this context, the purpose of this study is to relate the orofacial alterations that manifest during antineoplastic pharmacological treatment, highlighting the drugs commonly related to orofacial neuropathy and the adequate instrument to verify the alterations at clinical levels. METHODS: This prospective cohort study, addressed patients who would start therapy with taxanes, platinum, or related therapy...

Understanding the intricate processes of neuronal growth, degeneration, and neurotoxicity is paramount for unraveling nervous system function and holds significant promise in improving patient outcomes, especially in the context of chemotherapy-induced peripheral neuropathy (CIPN). These processes are influenced by a broad range of entwined events facilitated by chemical, electrical, and mechanical signals. The progress of each process is inherently linked to phenotypic changes in cells. Currently, the primary means of demonstrating morphological changes rely on measurements of neurite outgrowth and axon length...

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10-60 ppm of crude and alkaloid extracts derived from the leaves of Kratom ( Mitragyna speciosa (Korth...

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments...

The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse...

INTRODUCTION: Neoadjuvant therapy has become a standard treatment for patients with stage II/III HER2 positive and triple negative breast cancer, and in well-selected patients with locally advanced and borderline resectable high risk, luminal B breast cancer. Side effects of neoadjuvant therapy, such as fatigue, cardiotoxicity, neurotoxicity, anxiety, insomnia, vasomotor symptoms, gastrointestinal disturbance as well as a raft of immune-related adverse events, may impact treatment tolerance, long-term outcomes, and quality of life...

Topical 5-Fluorouracil (5-FU) is an antineoplastic chemotherapy drug used to treat precancerous and cancerous skin growths, such as actinic keratoses (AKs), squamous cell carcinoma in situ, and superficial basal cell carcinoma. The topical agent may rarely cause neurotoxic adverse effects. Multiple cases of systemic 5-FU and capecitabine chemotherapy-induced neuropathies have been reported. However, until now, the topical administration of the drug has not been reported to cause neurotoxicity. We present a case of an 83-year-old male who was prescribed topical 5-FU 5% cream to treat AKs on the left anterior scalp and returned weeks later with the development of focal neurotoxicity in the treatment area...

BACKGROUND: Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy. METHODS: Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected...