RESUMEN
Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07-1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26-100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.
Asunto(s)
Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Vincristina , Humanos , Vincristina/efectos adversos , Vincristina/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Niño , Femenino , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Preescolar , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Adolescente , Estudios Retrospectivos , Proteínas de Ciclo Celular/genética , Lactante , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Predisposición Genética a la Enfermedad , Genotipo , Alelos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Proteínas Asociadas a MicrotúbulosAsunto(s)
Antineoplásicos Fitogénicos , Neoplasias Endometriales , Paclitaxel , Penfigoide Ampolloso , Humanos , Femenino , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Anciano , Persona de Mediana EdadRESUMEN
BACKGROUND: Paclitaxel (PTX) is an essential cytotoxic anticancer agent and a standard treatment regimen component for various malignant tumors, including advanced unresectable non-small cell lung cancer, thymic cancer, and primary unknown cancers. However, chemotherapy-induced peripheral neuropathy (CIPN) caused by PTX is a significant adverse event that may lead to chemotherapy discontinuation and deterioration of the quality of life (QOL). Although treatment modalities such as goshajinkigan (GJG), pregabalin, and duloxetine are empirically utilized for CIPN, there is no established evidence for an agent as a preventive measure. We designed a randomized phase II trial (OLCSG2101) to investigate whether prophylactic GJG administration can prevent the onset of CIPN induced by PTX. METHODS: This study was designed as a two-arm, prospective, randomized, multicenter phase II trial. The patients will be randomly assigned to either the GJG prophylaxis arm (Arm A) or the GJG non-prophylaxis arm (Arm B), using cancer type (lung cancer or not) and age (<70 years or not) as adjustment factors. A total of 66 patients (33 in each arm) will be enrolled. DISCUSSION: The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL. ETHICS AND DISSEMINATION: Ethical approval was obtained from the certified review board of Okayama University (approval no. CRB21-005) on September 28, 2021. Results will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION: Japan Registry of Clinical Trials (registration number jRCTs061210047).
Asunto(s)
Medicamentos Herbarios Chinos , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Ensayos Clínicos Fase II como Asunto , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects and main reasons for affecting quality of life and dose reduction or even discontinuation of treatment in breast cancer patients. One of the most widely prescribed chemotherapies is the "taxanes." Considering that duloxetine has been used in treating neuropathies in recent years, this study aimed to investigate its effectiveness in preventing taxane-related neuropathy. MATERIAL AND METHODS: This is a randomized controlled trial on 47 patients: 24 received a placebo and 23 received duloxetine at 30 mg daily in the first week following the injection of paclitaxel and 60 mg during the second week in each chemotherapy cycle. Patients objective (nerve conduction velocity (NCV) values) and subjective symptoms (visual analog scale including; neuropathy, paresthesia, pain, cold sensitivity, and numbness), the grades of the patients' neuropathy (calculated according to Common Terminology Criteria for Adverse Events (CTCAE) v.5), and the presence of complications, before and after each chemotherapy cycle, were recorded. RESULTS: The placebo group experienced significantly higher occurrences of new neuropathy (8/23 in duloxetine vs 16/24 in placebo, P = 0.029) in NCV by tibial nerve latency (- 0.28% vs 19.87%, P = 0.006), tibial amplitude (4.40% vs - 10.88%, P = 0.049), and median nerve latency (8.72% vs 31.16%, P = 0.039); administration of duloxetine significantly reduced the scores of neuropathies (P < 0.001), pain (P = 0.027), during chemotherapy, and 6 weeks later; however, no significant effect was observed on paresthesia, numbness, cold sensitivity, and other NCV measurements. CONCLUSIONS: Paclitaxel can cause neuropathy, lasting for a long time. Our study showed duloxetine is potentially an effective medication that can prevent subjective and objective neuropathy.
Asunto(s)
Antineoplásicos Fitogénicos , Neoplasias de la Mama , Clorhidrato de Duloxetina , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Humanos , Clorhidrato de Duloxetina/administración & dosificación , Clorhidrato de Duloxetina/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Femenino , Método Doble Ciego , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Adulto , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Calidad de Vida , AncianoRESUMEN
Vincristine (VCR) is one of the most widely used chemotherapy agents in treating pediatric cancer. Nonetheless, it is known to cause dose-dependent neurotoxicity which can impact virtually every organ system. Despite its widespread use, the precise impact of VCR on the lower urinary tract (LUT) remains inadequately elucidated. Our initial clinical and translational investigations suggest a sex-specific influence of childhood VCR exposure on LUT function. Thus, the current study aimed to investigate the late effects of systemic VCR exposure on LUT physiology and the underlying mechanisms, focusing on dosage and male-sex, employing juvenile CD-1 mice as a model. Male mice subjected to VCR exhibited augmented functional bladder capacity accompanied by frequent non-void contractions during awake cystometry, alongside mast cell accumulation within the bladder, compared to the saline-treated control group. Noteworthy functional changes were observed in bladder strips from the VCR group, including decreased nerve-mediated contraction, heightened contractile responses to cholinergic and purinergic agonists, enhanced responsiveness to histamine-primarily via histamine receptor 1 (Hrh1)-and an augmented relaxation effect with compound 48/80 (a mast cell degranulator), relative to the control group. Significant changes in gene expression levels associated with neuroinflammation and nociception were observed in both the bladder and lumbosacral dorsal root ganglia (Ls-DRG) of the VCR group. These findings suggest that VCR exposure during childhood, particularly in males, triggers neuroimmune responses in the bladder and Ls-DRG, amplifying responsiveness to neurotransmitters in the bladder, thereby contributing to LUT dysfunction characterized by a mixed bladder phenotype as a late effect during survivorship.
Asunto(s)
Vejiga Urinaria , Vincristina , Animales , Masculino , Ratones , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Femenino , Vincristina/efectos adversos , Vincristina/farmacología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Humanos , Factores Sexuales , Relación Dosis-Respuesta a Droga , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.
Asunto(s)
Estudios de Factibilidad , Enfermedades del Sistema Nervioso Periférico , Vincristina , Humanos , Vincristina/efectos adversos , Vincristina/administración & dosificación , Femenino , Masculino , Kenia , Preescolar , Niño , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Lactante , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Estudios de Seguimiento , AdolescenteRESUMEN
OBJECTIVES: To explore the experiences of utilising distal-extremity cryotherapy in reducing chemotherapy-induced peripheral neuropathy during Paclitaxel treatment on physical functioning, clinical and patient-reported outcomes, compared to standard care in people affected by breast cancer. METHODS: Four databases and one register were searched on 11 April 2023 to identify all relevant studies meeting the inclusion and exclusion criteria. These were CINAHL (via EBSCOhost), Cochrane Central Register of Controlled Trials, Medline (via EBSCOhost), Scopus, and Web of Science Core Collection, with no limiters placed on any of the searches. Additionally, relevant systematic reviews were scrutinised for potentially relevant studies for screening. RESULTS: Distal-extremity cryotherapy is a safe intervention with minimal risk for serious adverse events. However, insufficient data supports the mainstay clinical use of cryotherapy in reducing chemotherapy-induced peripheral neuropathy from Paclitaxel use within the breast cancer population. Heterogeneity in study design, cryotherapy mode, and measurement tools underscore the need for additional research. CONCLUSION: Despite limited data on the impact of distal-extremity cryotherapy in preventing chemotherapy-induced peripheral neuropathy, there are valuable implications for nursing practice arising from this review. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a vital role in the clinical and experiential journey of people with breast cancer, it is important that they understand the available evidence and act as patient advocates. Assisting patients in understanding current research and encouraging participation in future studies, thereby enhancing our knowledge, and strengthening the available evidence base.
Asunto(s)
Neoplasias de la Mama , Crioterapia , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Humanos , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Crioterapia/métodos , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéuticoRESUMEN
BACKGROUND: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients. AIM: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex. MATERIALS AND METHODS: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined. RESULTS: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy. CONCLUSION: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.
Asunto(s)
Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Glándulas Salivales , Animales , Paclitaxel/efectos adversos , Paclitaxel/farmacología , Glándulas Salivales/efectos de los fármacos , Glándulas Salivales/patología , Glándulas Salivales/metabolismo , Ratas , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacología , Ratas Wistar , Estrés Oxidativo/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Complejo Vitamínico B/farmacología , Complejo Vitamínico B/uso terapéutico , Masculino , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Catalasa/metabolismoRESUMEN
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity. METHODS: Pre-treatment serum concentrations of 20 amino acids were measured in the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acids and CIPN severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction. The network of metabolic pathways of amino acids was analyzed using over-representation analysis. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm. RESULTS: In the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In secondary analyses, higher concentrations of four amino acids, glutamate (ß = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (ß = 0.54 [0.19, 0.89], p = 0.002), tyrosine (ß = 0.57 [0.23, 0.91], p = 0.001), and valine (ß = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality. CONCLUSIONS: This analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged.
Asunto(s)
Aminoácidos , Neoplasias de la Mama , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Humanos , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Aminoácidos/sangre , Persona de Mediana Edad , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Anciano , Adulto , Índice de Severidad de la EnfermedadRESUMEN
This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.
Asunto(s)
Fuerza de la Mano , Mano , Linfoma , Vincristina , Humanos , Vincristina/efectos adversos , Vincristina/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Linfoma/tratamiento farmacológico , Anciano , Adulto , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Hipoestesia/inducido químicamenteRESUMEN
BACKGROUND: Nanoparticle polymeric micellar paclitaxel (NPMP) is a novel Cremophor EL (CrEL)-free nanoparticle micellar formulation of paclitaxel. This study evaluated the efficacy and toxicity of NPMP in the treatment of patients with advanced gastric cancer (AGC). METHODS: Patients with histologically confirmed AGC in Jiangsu Cancer Hospital were retrospectively collected and divided into two groups. Patients in group A received NPMP at a total dose of 360 mg/m2 each cycle, and patients in group B were given paclitaxel at a dose of 210 mg/m2 each cycle. In addition, all patients received 5-fluorouracil at a dose of 0.75 g/m2 on days 1-4 and leucovorin at a dose of 200 mg/m2 on days 1-4 for at least 2 cycles. RESULTS: From January 2021 to May 2023, 63 patients (32 in group A and 31 in group B) could be evaluated for treatment response. A marked disparity in the overall response was observed between groups A and B, indicating statistical significance. The overall response rate was 31% in group A (10/32) and 10% in group B (3/31) (P = 0.034). Disease control rate was 91% in group A (29/32) and 81% in group B (25/31) (P = 0.440). No statistically significant difference in adverse reactions was observed between the two groups. However, the incidence of anemia, leucopenia, nausea, vomiting, diarrhea, liver dysfunction, and allergy in group A was notably lower than that in group B. CONCLUSIONS: NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.
Asunto(s)
Micelas , Nanopartículas , Paclitaxel , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Nanopartículas/administración & dosificación , Estudios Retrospectivos , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Resultado del Tratamiento , Leucovorina/uso terapéutico , Leucovorina/administración & dosificaciónRESUMEN
BACKGROUND: Paclitaxel hypersensitivity reactions (HSRs) are prevalent, especially in females. The common paclitaxel pretreatment, dexamethasone, may inhibit chemotherapy efficacy and accelerate tumor progression. We aimed to balance paclitaxel HSRs and the lowest dexamethasone dose for gynecologic malignancies. METHODS: We retrospectively examined 1,074 cycles of 3-weekly paclitaxel-containing treatment for 231 gynecologic malignancies at Xiangya Hospital. HSR incidence with different dexamethasone regimens was the primary outcome. Risk factors were examined in all cycles using univariate and multivariate models with generalized estimating equations. A subgroup analysis of initial exposure to paclitaxel was also conducted. RESULTS: HSR occurred in 33 patients (14.29%) and 49 cycles (4.56%), including 69.39% in cycles 1-2. There were no severe HSRs (grade ≥3). Different premedication regimens, including dexamethasone dosage and route, ranitidine presence or absence, didn't affect HSR incidence in univariate and multivariate analyzes (p > 0.05). Premenopausal women exerted fewer HSRs (ORadj 0.22, 95%CI 0.08-0.58; p = 0.002). At the first exposure to paclitaxel, more than 10 mg of dexamethasone didn't diminish HSRs (OR 0.83, 95%CI 0.27-2.59; p = 0.753). CONCLUSIONS: In gynecologic malignancies, 10 mg dexamethasone along with 20 mg diphenhydramine may be adequate to prevent paclitaxel HSRs without ranitidine. It is necessary to reevaluate paclitaxel premedication regimens.
Asunto(s)
Antineoplásicos Fitogénicos , Dexametasona , Relación Dosis-Respuesta a Droga , Hipersensibilidad a las Drogas , Neoplasias de los Genitales Femeninos , Paclitaxel , Humanos , Femenino , Dexametasona/administración & dosificación , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios Retrospectivos , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Persona de Mediana Edad , Hipersensibilidad a las Drogas/prevención & control , Hipersensibilidad a las Drogas/etiología , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Factores de Riesgo , IncidenciaRESUMEN
BACKGROUND: Rhabdomyosarcoma (RMS) is a rare cancer that develops in soft tissue, particularly skeletal muscle tissue and occasionally hollow organs like the bladder or uterus. Vincristine (VCR) is the main therapy used in treatment of RMS, it is an alkaloid produced from vinca and it is one of the most commonly prescribed drugs in pediatric oncology for the treatment of a number of tumors. The CYP3A5 enzyme is responsible for vincristine metabolism. The effect of CYP3A5 genetic polymorphism on the efficacy and toxicity of VCR on RMS patients still needs further research. METHODS: Genotyping for CYP3A5 SNPs rs776746, rs10264272 and rs41303343 was performed using Taqman Real-Time PCR assays in a retrospective cohort study of 150 RMS pediatric patients treated with vincristine. The relationship between these genotypes and RMS survival was then examined. RESULTS: We found that patients with CYP3A5*3/*3 had the highest incidence of vincristine-induced neuropathy reaching 61.3%. Patients with CYP3A5*1/*3, CYP3A5*3/*6 and the normal metabolizers with CYP3A5*1/*1 had frequencies of 22%, 10.7%, and 4.7%. patients with the lowest frequency of 1.3% were those with the CYP3A5*1/*6 genotype. There was no correlation between the genotypes of CYP3A5*3, CYP3A5*6, CYP3A5*7, and RMS survival. Initial risk, metastasis, response, convulsions, unsteady gait and hepatotoxicity grade had a significant effect on overall survival with p<0.05. CONCLUSION: CYP3A5*1/*1 have less severe vincristine-induced neuropathy than CYP3A5 *1/*3, CYP3A5 *1/*6 and CYP3A5 *3/*3, CYP3A5 *3/*6. There is a significant influence of CYP3A5 mutation on neuropathy grade and assist of ADL as a part of neurotoxicity.
Asunto(s)
Antineoplásicos Fitogénicos , Citocromo P-450 CYP3A , Polimorfismo de Nucleótido Simple , Rabdomiosarcoma , Vincristina , Humanos , Vincristina/efectos adversos , Citocromo P-450 CYP3A/genética , Femenino , Masculino , Estudios Retrospectivos , Rabdomiosarcoma/genética , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/patología , Niño , Preescolar , Egipto , Pronóstico , Antineoplásicos Fitogénicos/efectos adversos , Estudios de Seguimiento , Tasa de Supervivencia , Genotipo , Lactante , AdolescenteRESUMEN
BACKGROUND: Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). HYPOTHESIS/OBJECTIVES: Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. ANIMALS: One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine. METHODS: A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression. RESULTS: Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). CONCLUSIONS AND CLINICAL IMPORTANCE: Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.
Asunto(s)
Antineoplásicos Fitogénicos , Peso Corporal , Enfermedades de los Perros , Linfoma , Vincristina , Animales , Perros , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Linfoma/veterinaria , Linfoma/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Peso Corporal/efectos de los fármacos , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/veterinariaRESUMEN
BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.
Asunto(s)
Diarrea , Irinotecán , Irinotecán/efectos adversos , Diarrea/prevención & control , Diarrea/inducido químicamente , Humanos , Neoplasias/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéuticoRESUMEN
Nab-paclitaxel-related cystoid macular edema is a rare ophthalmic adverse drug reaction. We present a 54-year-old woman with metastatic hormone receptor positive, HER-2 negative breast carcinoma who developed profound bilateral vision loss after the seventh cycle of nab-paclitaxel treatment. Optical coherence tomography and macula microperimetry demonstrated macular edema and decreased threshold sensitivity, respectively. Cessation of nab-paclitaxel improved structural and functional vision after 4 weeks. The introduction of topical dorzolamide 1% in one eye demonstrated further rapid resolution of edema. We demonstrate the objective and subjective visual changes and recovery of nab-paclitaxel-related cystoid macular edema. [Ophthalmic Surg Lasers Imaging Retina 2024;55:408-411.].
Asunto(s)
Albúminas , Neoplasias de la Mama , Mácula Lútea , Edema Macular , Paclitaxel , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/inducido químicamente , Femenino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Tomografía de Coherencia Óptica/métodos , Neoplasias de la Mama/tratamiento farmacológico , Albúminas/efectos adversos , Mácula Lútea/patología , Antineoplásicos Fitogénicos/efectos adversos , Pruebas del Campo Visual , Campos Visuales/fisiologíaRESUMEN
BACKGROUND: Characteristics of taxane-induced peripheral neuropathy (PN) could be different between paclitaxel and nab-paclitaxel. The purpose of this prospective observational multicenter cohort study was to compare tri-weekly nab-paclitaxel to weekly standard paclitaxel regarding the severity, onset and recovery of sensory and motor PN in patients with breast cancer. METHODS: Patients with histologically confirmed breast cancer who were scheduled to receive standard weekly paclitaxel (80 mg/m2) or tri-weekly nab-paclitaxel (260 mg/m2) at institutions in our multicenter group were eligible for this study. Sensory and motor PN were evaluated every 3 weeks until PN improved for up to one year using patient-reported outcome. RESULTS: Between February 2011 and April 2013, 115 patients were enrolled, including 57 and 58 in the paclitaxel and nab-paclitaxel groups, respectively. The incidence of moderate or severe sensory PN was not significantly different between the two groups (p = 0.40). The incidence of moderate or higher motor PN was more frequent in the nab-paclitaxel group than in the paclitaxel group (p = 0.048). The median period for demonstrating PN were shorter in the nab-paclitaxel group than in the paclitaxel group (sensory, p = 0.003; motor, p = 0.001). The recovery of motor PN was slower in the nab-paclitaxel group than in the paclitaxel group (p = 0.035), while the recovery period of sensory PN was not statistically different. CONCLUSION: Nab-paclitaxel induced sensory PN sooner than paclitaxel, and no difference was observed in the severity and recovery duration between the two agents. Motor PN was more severe, started sooner, and improved over a longer period in the nab-paclitaxel-treated patients than in the paclitaxel-treated patients.
Asunto(s)
Albúminas , Neoplasias de la Mama , Paclitaxel , Medición de Resultados Informados por el Paciente , Enfermedades del Sistema Nervioso Periférico , Humanos , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Estudios Prospectivos , Anciano , Adulto , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéuticoRESUMEN
PURPOSE: To evaluate the short-term safety of albumin-bound paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) during and after gastric cancer (GC) surgery. METHODS: A retrospective analysis of clinical data was conducted for GC surgery patients at Zhongnan Hospital of Wuhan University, from January 2020 to September 2022. The study group (n = 120) received HIPEC and the control group (n = 268) did not receive albumin-bound paclitaxel. Short-term safety indicators including intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery were compared between the two groups. RESULTS: There were no statistically significant differences between the two groups regarding intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery time (P > 0.05 for all). In the study group, patients were further divided into subgroups based on dose and timing. Subgroup analysis revealed no significant differences among the different dose subgroups. However, when focusing on timing subgroups, the postoperative subgroup exhibited significantly higher white blood cell counts and bilirubin levels compared to the intraoperative subgroup, while the intraoperative subgroup had significantly higher bilirubin levels compared to both postoperative and intraoperative plus postoperative subgroups. CONCLUSION: Albumin-bound paclitaxel demonstrates good safety and tolerability in HIPEC during and after GC surgery, without increasing the risk of intraoperative complications.
Asunto(s)
Paclitaxel Unido a Albúmina , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Masculino , Quimioterapia Intraperitoneal Hipertérmica/métodos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Paclitaxel Unido a Albúmina/administración & dosificación , Paclitaxel Unido a Albúmina/uso terapéutico , Anciano , Adulto , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVE: Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters. METHODS: Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2. RESULTS: From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C>A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06-3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00-1.06). In addition, CES1 c.1165-41C>T and CES1 n.95346T>C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20-0.90 and P = 0.018, OR 0.23, 95% CI 0.08-0.79, respectively). CONCLUSION: Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.