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Aluminum (Al3+) is environmentally abundant and can harm living organisms in various ways, such as by inhibiting root growth, damaging faunal nervous systems, and promoting tumor cell proliferation. However, the dynamics of Al3+ in living organisms are largely unknown; thus, detecting Al3+ in the environment and organisms is crucial. Fluorescent probes are useful tools for the selective detection of metal ions. In particular, ratiometric fluorescent probes exhibit a detection response at two different maximum fluorescence emission wavelengths; which is advantageous for avoiding the influence of background fluorescence. A novel pyrone-fused tricyclic scaffold-based ratiometric fluorescent probe for detecting Al3+, ethyl 11-imino-1-oxo-3-phenyl-1H,11H-pyrano[4,3-b] quinolizine-5-carboxylate (PQ), was developed in this study. The PQ fluorescence blue shifted from 505 to 457 nm upon the addition of Al3+. The blue shift was accompanied by a change in the fluorescence color of the PQ solution from green to blue. Fluorescence titration experiments demonstrated that the fluorescence intensity ratio at the two peaks of interest (457/505 nm) increased in a concentration-dependent manner upon the addition of Al3+. Moreover, this study demonstrated that a PQ-soaked paper displays a visible color change under ultraviolet light upon exposure to Al3+. The above results suggest that PQ is an effective ratiometric probe for the detection of Al3+ in the environment. Future studies will be conducted to introduce various substituents and develop fluorescent probes by leveraging the fluorescence property of a pyrone-fused tricyclic scaffolds.
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The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole-4,9-dione compounds (5a-e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a-e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole-4,9-dione skeleton and substituent effect, 5a-e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b-e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a-e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future.
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Testes de Sensibilidade Microbiana , Tiazóis , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus/efeitos dos fármacos , Staphylococcus/crescimento & desenvolvimento , Estrutura Molecular , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologiaRESUMO
BACKGROUND: Al exists naturally in the environment and is an important component in acidic soils, which harm almost all plants. Furthermore, Al is widely used in food additives, cosmetics, and medicines, resulting in living organisms ingesting traces of Al orally or dermally every day. Accordingly, Al accumulates in the body, which can cause negative bioeffects and diseases, and this concern is gaining increasing attention. Therefore, to detect and track Al in the environment and in living organisms, the development of novel Al-selective probes that are water-soluble and exhibit fluorescence at long wavelengths is necessary. RESULTS: In this study, an Al3+-selective fluorescent probe PSP based on a novel pyrone molecule was synthesized and characterized to detect and track Al in biological systems. PSP exhibited fluorescence enhancement at 580 nm in the presence of Al3+ in aqueous media. Binding analysis using Job's plot and structural analysis using 1H NMR showed that PSP formed a 1:1 complex with Al3+ at the two carbonyl groups of the dimethyl malonate of the pyrone ring. Upon testing in biological systems, PSP showed good cell membrane permeability, detected intracellular Al3+ in human breast cancer cells (MDA-MB-231), and successfully imaged accumulated Al3+ in Microcystis aeruginosa and the larvae of Rheocricotopus species. SIGNIFICANCE: The novel Al3+-selective fluorescent probe PSP is highly effective and is expected to aid in elucidating the role of Al3+ in the environment and living organisms.
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Corantes Fluorescentes , Água , Humanos , Corantes Fluorescentes/química , Água/química , Pironas , Alumínio/análise , Espectrometria de Fluorescência/métodosRESUMO
BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. PATIENTS AND METHODS: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. RESULTS: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.
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Neoplasias da Mama , Neutropenia , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos Retrospectivos , Neutropenia/induzido quimicamente , Fatores de Risco , Resultado do TratamentoRESUMO
Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12-0.66; P = 0.004 for baseline anemia, 0.18; 0.08-0.42; P < 0.0001 for prophylactic G-CSF administration). The primary cause of the reduction was febrile neutropenia, and the same factors were identified. Our study revealed that patients with baseline anemia and prophylactic G-CSF administration have less risk for treatment reduction in DOC + RAM for NSCLC treatment.
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Anemia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/uso terapêutico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anemia/etiologia , RamucirumabRESUMO
Therapy for patients of metastatic breast cancer based on palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has been approved in Japan. However, the risk factors for palbociclib-induced severe neutropenia in Japanese patients are rarely reported. Hence, the present study is aimed to identify the risk factors for adverse events requiring palbociclib dose reduction or discontinuation, and to identify the factors necessary to identify a more stable strategy for treatment continuation. This retrospective cohort analysis included patients with advanced breast cancer treated with 125 mg/d palbociclib. We demonstrated that severe neutropenia required significant dose reduction or therapy cessation. Most (77%) of the patients had severe neutropenia within the three courses. Risk factors for grade 3 or higher included low neutrophil counts (< 3250 /µL) before treatment [odds ratio (OR) = 9.10, 95% confidence interval (CI) (2.80-29.41), p < 0.001] and high age-adjusted Charlson comorbidity index (> 9) [OR = 1.64, 95% CI (1.09-2.48), p = 0.018]. Thus, low baseline neutrophil counts and high values for Age-adjusted Charlson comorbidity index are prospective predictive markers for palbociclib-induced severe neutropenia.
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Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Neutropenia , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , População do Leste Asiático , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Estudos Prospectivos , Receptor ErbB-2 , Estudos Retrospectivos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND/AIM: Alectinib is recommended for anaplastic lymphoma kinase fusion gene-positive non-small cell lung cancer. We have experienced early alectinib discontinuation due to disease progression and adverse effects in real world. Because alectinib has a high protein-binding rate of >99%, low serum albumin may increase the concentration of free drug and affect efficacy and adverse events. However, no association between serum albumin and the clinical impact of alectinib has been reported. The purpose of this study was to determine the effect of serum albumin on time-to-treatment failure (TTF) in alectinib. PATIENTS AND METHODS: Fifty-six patients who were admitted to four hospitals (National Hospital Organization Hokkaido Cancer Center, Sapporo Minami-Sanjo Hospital, KKR Sapporo Medical Center, Otaru General Hospital) between October 2014 and September 2020 were retrospectively evaluated to identify those treated with alectinib. RESULTS: The multivariate analysis showed that the risk of discontinuation was significantly higher with serum albumin <3.6 g/dl compared to ≥3.6 g/dl at the start of alectinib administration (hazard ratio=3.00; 95% confidence interval=1.36-6.66; p<0.01). On Kaplan-Meier curves, TTF for serum albumin <3.6 was significantly shorter than that for ≥3.6. (median TTF: 12.1 months vs. not reach, p<0.01). CONCLUSION: To the best of our knowledge, this study is the first to report that serum albumin <3.6 g/dl at alectinib induction is associated with poor TTF. Low serum albumin is a poor prognostic factor in cancer patients. Thus, serum albumin levels must be measured before treatment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Retrospectivos , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Albumina Sérica , Tempo para o Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma AnaplásicoRESUMO
INTRODUCTION: The association between abemaciclib dose reduction and treatment adherence is not clear. In this study, we examined real-world data of Japanese patients with advanced breast cancer (ABC) to determine how abemaciclib dose reduction is related to treatment continuation. METHODS: This retrospective observational study involved 120 consecutive patients with ABC who received abemaciclib from December 2018 to March 2021. The time to treatment failure (TTF) was estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with a TTF of >365 days (TTF365). RESULTS: According to the dose reduction during treatment, the patients were classified into 100, 200, and 300 mg/day abemaciclib groups. The 300 mg/day group had a TTF of 7.4 months, whereas the 100 and 200 mg/day groups had significantly longer TTFs (17.9 and 17.3 months, respectively; P = 0.0002). In this study, relative to the 300 mg/day arm, TTF was improved in 200mg/day arm and 100 mg/day arm (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.33-0.93) and [HR], 0.37; 95% CI, 0.19-0.74). For patients who received 300mg/day of abemaciclib dose arm, 200mg/day, and 100mg/day, the median TTF was 7.4 ,17.9 and 17.3 months. The frequently reported adverse effects (AEs) were anemia, increased blood creatinine levels, diarrhea, and neutropenia (90%, 83%, 83%, and 75% of the patients, respectively). Neutropenia, fatigue, and diarrhea were the top AEs causing dose reduction. A multivariate analysis that examined factors associated with achieving TTF 365 confirmed that dose down was an important factor (odds ratio: 3.95, 95% confidence interval: 1.68-9.36, P = 0.002). CONCLUSIONS: In this study, the 100 and 200 mg/day groups had a longer TTF than the 300 mg/day group, and dose reduction was identified as an important factor in achieving longer TTF.
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Neoplasias da Mama , Neutropenia , Humanos , Feminino , Resultado do Tratamento , Aminopiridinas/efeitos adversos , Benzimidazóis/efeitos adversos , Neutropenia/induzido quimicamente , Neoplasias da Mama/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). METHODS: We retrospectively analyzed clinical data for 36 patients with non-Hodgkin's lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUCactual) was calculated backward using a variant of the Calvert formula. RESULTS: The median AUCactual was 4.6 (interquartile range: 4.3-5.3) min mg/mL and AUCactual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUCactual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45-258; P = 0.02). CONCLUSION: This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.
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Linfoma não Hodgkin , Trombocitopenia , Humanos , Carboplatina , Incidência , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Etoposídeo , Área Sob a CurvaRESUMO
Background: Association between baseline medications plus neutrophil-to-lymphocyte ratio (NLR) and the effectiveness of immune checkpoint inhibitor (ICI) plus platinum doublet remains unknown, despite several reported prognostic models. We used real-world data to investigate whether baseline medications plus NLR predict survival outcomes in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICI plus platinum doublet. Methods: This multicenter, retrospective, observational study conducted in Japan between December 2018 and March 2021 used real-world data of consecutive patients with advanced NSCLC who received ICI (pembrolizumab or atezolizumab) plus platinum doublet as first-line treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The prognostic score for baseline medications plus NLR was weighted by regression ß coefficients and used to categorize patients into good, intermediate, and poor prognoses groups. In addition, time-dependent receiver operating characteristic curve analyses and univariable and multivariable Cox proportional hazards models were constructed. Results: Overall, 241 patients were included. Poor prognosis was significantly associated with worse PFS (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.08-2.94; P = 0.025) and OS (HR: 3.59; 95% CI: 2.05-6.28; P < 0.001) than good prognosis. Harrell's C-index for this prognostic model was 0.648. Conclusions: Baseline medication plus NLR could predict progressively worse survival outcomes in patients with advanced NSCLC receiving ICI plus platinum doublet and could be used as a prognostic index for poor outcomes.
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Boron neutron capture therapy (BNCT) is an attractive approach to treating cancers. Currently, only one 10B-labeled boronoagent (Borofalan, BPA) has been approved for clinical BNCT in Japan, and methods for predicting and measuring BNCT efficacy must be established to support the development of next-generation 10B-boronoagents. Fluorescence sensors targeting boronic acids can achieve this because the amount and localization of 10B in tumor tissues directly determine BNCT efficacy; however, current sensors are nonoptimal given their slow reaction rate and weak fluorescence (quantum yield < 0.1). Herein, we designed and synthesized a novel small molecular-weight fluorescence sensor, BITQ, targeting boronic acids. In vitro qualitative and quantitative properties of BITQ were assessed using a fluorophotometer and a fluorescence microscope together with BPA quantification in blood samples. BITQ exhibited significant quantitative and selective fluorescence after reacting with BPA (post-to-pre-fluorescence ratio = 5.6; quantum yield = 0.53); the fluorescence plateaued within 1 min after BPA mixing, enabling the visualization of intracellular BPA distribution. Furthermore, BITQ quantified the BPA concentration in mouse blood with reliability comparable with that of current methods. This study identifies BITQ as a versatile fluorescence sensor for analyzing boronic acid agents. BITQ will contribute to 10B-boronoagent development and promote research in BNCT.
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The amount and localization of boron-10 atoms delivered into tumor cells determines the therapeutic effect of boron neutron capture therapy (BNCT) and, consequently, efforts have been directed to develop fluorescence sensors to detect intracellular boronic acid compounds. Currently, these sensors are blue-emitting and hence are impracticable for co-staining with nucleus staining reagents, such as DAPI and Hoechst 33342. Here, we designed and synthesized a novel fluorescence boron sensor, BS-631, that emits fluorescence with a maximum emission wavelength of 631 nm after reaction with the clinically available boronic acid agent, 4-borono-l-phenylalanine (BPA). BS-631 quantitatively detected BPA with sufficiently high sensitivity (detection limit = 19.6 µM) for evaluating BNCT agents. Furthermore, BS-631 did not emit fluorescence after incubation with metal cations. Notably, red-emitting BS-631 could easily and clearly visualize the localization of BPA within cells with nuclei co-stained using Hoechst 33342. This study highlights the promising properties of BS-631 as a versatile boron sensor for evaluating and analyzing boronic acid agents in cancer therapy.
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Terapia por Captura de Nêutron de Boro , Boro , Compostos de Boro , Ácidos Borônicos , Linhagem Celular Tumoral , Fluorescência , FenilalaninaRESUMO
This study aimed to investigate whether renin-angiotensin system inhibitors (RAS-I) have an advantage over calcium channel blockers (CCB) for suppression of proteinuria in hypertensive patients with gastric cancer receiving ramucirumab (RAM) treatment. Adult Japanese patients with gastric cancer who were outpatients at Asahikawa Medical University Hospital, National Hospital Organization Hokkaido Cancer Center, and Iwate Medical University Hospital between July 1, 2015, and March 31, 2021, were included in this study. Of these patients, those who had received first-time RAM treatment, and those treated with antihypertensive agents including RAS-I or a CCB at initial RAM administration were included. A total of 36 patients were analyzed in this study. Of these patients, 17 patients were classified into the RAS-I group and the remaining 19 into the CCB group. After 12 weeks of RAM administration, the prevalence of proteinuria in the RAS-I group was significantly lower than that in the CCB group. Additionally, Kaplan-Meier analysis showed that the cumulative occurrence of proteinuria in the RAS-I group over 12 weeks following RAM administration was significantly lower than that in the CCB group. Furthermore, simulation of the time course of RAM blood concentrations based on the O'Brien model showed that there may not be differences in the RAM blood concentration profiles over 12 weeks between the two groups. RAS-I may have an advantage over CCB for suppressing proteinuria in hypertensive patients with gastric cancer treated with blood pressure antihypertensive agents. Our results provide useful information to healthcare professionals involved in the administration of RAM treatment.
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Since the therapeutic effect of boron neutron capture therapy is influenced by the intracellular distribution profile of boronoagents containing 10B atoms, it is necessary to establish a method that can determine the intracellular distribution profile of boronoagents. We aimed to develop a small molecule-based fluorescence sensor that changes its fluorescence properties upon complexation with the boronic acid moiety of a boronoagent. Thus, we designed a 2-(2-pyridyl)phenol derivative PPN-1 by introducing a N,O ligand substructure into a zinc sensor probe with excellent fluorescence properties. To investigate the effectiveness of PPN-1, we synthesized PPN-1 and evaluated its fluorescence properties compared to DAHMI, a current available boronic acid sensor. Consequently, PPN-1 showed favorable off/on fluorescence switching ability with a large Stokes shift after the addition of p-boronophenylalanine (BPA). Notably, after adding BPA, PPN-1 exhibited a rapid increase and reached a fluorescence plateau within 5 min, which is much shorter than the 2 h needed for DAHMI. Further, PPN-1 has excellent selectivity and detection and quantification limits similar to those of ICP-OES. These results demonstrated that PPN-1 is a practical scaffold for the detection and quantification of boronic acids and will provide essential insights for the development of boronic acid-targeted fluorescent sensors in the future.
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Terapia por Captura de Nêutron de Boro , Ácidos Borônicos , Compostos de Boro/química , Ácidos Borônicos/química , Ligantes , Fenóis , ZincoRESUMO
BACKGROUND: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios can indicate poor disease prognosis and are inflammation markers. We investigated the role of NLR and PLR as effective predictive markers of immune-related adverse event (irAE) onset in patients treated with nivolumab. METHODS: We retrospectively analysed 73 gastric and renal cancer patients treated with nivolumab at the Hokkaido Cancer Centre from January 2017 to June 2020. NLR and PLR were calculated at the initiation of nivolumab treatment and irAE onset. We identified the risk factors for Grade 3-4 irAE onset using NLR, PLR, sex, cancer type, and age. Overall survival (OS) and progression free survival (PFS) were calculated from the initiation of nivolumab treatment to the date of death or censored at last follow-up. RESULTS: Among the 73 patients included, 17 (18%) had at least one grade3-4 irAE. Multivariable logistic regression analyses revealed that pretreatment NLR<4.3 was significantly associated with a reduced risk for onset of grade3-4 irAEs, whereas rate of NLR change after treatment, ΔNLR>120% was significantly associated with an increased risk. CONCLUSIONS: NLR is an effective marker for prognosis and onset of grade 3-4 irAEs.
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Antineoplásicos Imunológicos/efeitos adversos , Contagem de Células Sanguíneas , Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Nivolumabe/efeitos adversos , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Plaquetas/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Modelos Logísticos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/imunologia , Taxa de SobrevidaRESUMO
AIMS: Symptomatic treatment is insufficient for chemotherapy- or targeted therapy-induced oral mucositis (OM) pain, and benzydamine mouthwash is not commercially available in Japan. We evaluated the analgesic effects of an in-hospital preparation of 0.25% indomethacin spray (IMS) on anticancer drug-induced OM pain. METHODS: This single-arm prospective trial enrolled 20 patients (median age 62.0 years) with OM and numerical rating scale scores of ≥5 who were undergoing chemotherapy or targeted therapy in our hospital. Pain scores were recorded using a visual analog scale (VAS) before and 30 min after IMS administration. Pain relief (PR) scores were recorded at 15, 30, and 60 min after IMS administration; total PR after 60 min (TOTPAR60 ) was calculated, and the mean PR score after 3 days (PR3days ) was determined. RESULTS: The median (interquartile range) OM grade of the participants was 2.0 (2.0-2.3). The VAS score decreased significantly at 30 min after IMS administration (p = .001). The median (interquartile range) TOTPAR60 and PR3days were 6.0 (3.8-7.3) and 2.0 (2.0-3.0), respectively. CONCLUSIONS: IMS helped improve patients' quality of life. The risk of systemic adverse effects was low because of the low dose administered. IMS effectively relieved anticancer drug-induced OM pain and may be useful for immediate self-medication.
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Neoplasias , Preparações Farmacêuticas , Estomatite , Analgésicos/uso terapêutico , Estudos Transversais , Humanos , Indometacina/uso terapêutico , Japão , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Estudos Prospectivos , Qualidade de VidaRESUMO
Edema is a frequent side effect observed in patients receiving docetaxel hydrate(DTX)treatment. However, the factors contributing to the development of edema in breast cancer patients receiving this treatment have not been completely elucidated. In this study, we examined the electronic medical records of breast cancer patients who received 4 courses of DTX ± trastuzumab therapy at the Hokkaido Cancer Center between January 2017 and February 2018 to investigate the occurrence of edema and related factors. We found that edema was confirmed in 23(42.6%)of the 54 surveyed patients. Further, HER2- positive and high BNP levels before the start of treatment were shown to be factors related to edema development. In particular, the results suggested that when DTX is administered in combination with trastuzumab, it is necessary to monitor early and frequently the occurrence of edema.
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Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel , Edema , Humanos , Receptor ErbB-2 , Taxoides , TrastuzumabRESUMO
Medications that target programmed cell death protein-1 (PD-1) have proven effective. However, blockade of PD-1/Programmed death-ligand 1(PD-L1) causes immune-related adverse events (irAEs). Characteristics of this irAE include many symptom, low in frequency, and difficulty in prevention. The key to a successful ICI-related treatment lies in the management of irAEs resulting from immune checkpoint inhibitor (ICI) treatment. Although it is difficult to predict irAE, we tried to extract features of irAE expression from analysis of real-world database. This study used data extracted from the Japan Adverse Drug Event Report (JADER) database to assess risk factors associated with serious side effects of irAE, type 1 diabetes (T1DM). The analysis targets were nivolumab, atezolizumab, durvalumab, and pembrolizumab, and the study period was from July 2014 to June 2019. Analysis of Japanese population data confirmed that being women and having melanoma were risk factors for developing ICI-related T1DM. Analysis using this database in combination with information on ICI-related T1DM provides information and guidelines that will help in the safer treatment of ICI in the future.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Idade de Início , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. OBJECTIVE: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). METHODS: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. RESULTS: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. CONCLUSION: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.
Assuntos
Axitinibe/efeitos adversos , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/diagnóstico , Hipotireoidismo/induzido quimicamente , Neoplasias Renais/diagnóstico , Idoso , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Tireotropina/sangue , Resultado do TratamentoRESUMO
Background: Cetuximab-induced skin disorder is common in colorectal cancer (CRC), and is known to affect prolonged overall survival (OS). Patients with left-sided CRC survive longer than those with right-sided CRC, among those treated with combination cetuximab and chemotherapy. However, no study has evaluated patient prognosis in terms of OS and progression-free survival (PFS) in relation to both tumor location and skin disorder. This study aimed to determine the incidence of skin disorder according to tumor location and analyze the relationship of tumor location and skin disorder with OS. Methods: Patients with metastatic colorectal cancer (mCRC) treated with standard chemotherapy and cetuximab as first-line therapy were included. Differences in the incidence of skin disorders due to the location of the primary tumors were compared in the same patient. The OS and PFS in relation to the location of the primary tumors and presence or absence of skin disorder were also compared. Results: Total frequency of each skin disorder as rash acneiform, paronychia, and dry skin in patients with left- and right-sided mCRC was 70%, 70%, and 43% and 27%, 36%, and 27%, respectively. The median OS was 8.9 months for mCRC on the left-sided without skin disorder and 56.3 months for mCRC on the left-sided with skin disorder. In comparison, the median OS was 10.4 months for mCRC on the right-sided without skin disorder and 11.3 months for mCRC on the right-sided with skin disease (left-sided with skin disorder versus other three group; P<0.001). Conclusions: Primary tumor location and the presence of skin disorder are important factors in patients with mCRC who receive cetuximab. In particular, our results show the new fact that the left-sided and right-sided mCRC survival time were comparable if there is no skin disorder caused by cetuximab.