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1.
Br J Cancer ; 130(2): 224-232, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37973958

RESUMEN

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.


Asunto(s)
Antieméticos , Antineoplásicos , Humanos , Palonosetrón/uso terapéutico , Cisplatino/efectos adversos , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Antieméticos/uso terapéutico , Olanzapina/uso terapéutico , Dexametasona/efectos adversos , Vómitos/inducido químicamente , Calidad de Vida , Quinuclidinas/efectos adversos , Antineoplásicos/efectos adversos
2.
Gan To Kagaku Ryoho ; 42(6): 705-8, 2015 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-26199241

RESUMEN

Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung cancer patients with impaired renal function treated between May 2009 and May 2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and 17 patients had a creatinine clearance rate (Ccr) of <45 mL/min and ≥45 mL/min, respectively. The median age was higher in the Ccr<45 mL/min group (78.9 years) than in the ≥45 mL/min group (65.2 years). The rate of neutropenia above Grade 3 was 30% in the Ccr<45 mL/min group and 6% in the ≥45 mL/min group. Therefore, reducing the dose of pemetrexed should be considered in patients with impaired renal function. Non-hematologic toxicities were not correlated with the renal function. There was no treatment-related death, and most of the toxicities were mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr<45 mL/min group, and in 12 patients (70%) in the Ccr≥45 mL/min group, although some patients in both groups showed neither complete nor partial responses. The disease control rate and median progression-free survival time were 60% and 2.8 months in the Ccr<45 mL/min group, and 70% and 2.9 months in the Ccr≥45 mL/min group, respectively. Thus, in this analysis, treatment with pemetrexed resulted in clinically equivalent efficacy in advanced non-small-cell lung cancer patients regardless of the state of renal function.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Insuficiencia Renal/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Femenino , Glutamatos/efectos adversos , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pemetrexed , Insuficiencia Renal/inducido químicamente , Estudios Retrospectivos
3.
Lung Cancer ; 192: 107801, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38678830

RESUMEN

BACKGROUND: Mirtazapine blocks 5-hydroxytryptamine type (5-HT)2A, 5-HT2C, 5-HT3 and histamine H1 receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers. METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h). RESULTS: Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0. CONCLUSIONS: Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.


Asunto(s)
Antieméticos , Carboplatino , Dexametasona , Granisetrón , Mirtazapina , Náusea , Vómitos , Humanos , Granisetrón/administración & dosificación , Granisetrón/uso terapéutico , Masculino , Mirtazapina/uso terapéutico , Mirtazapina/administración & dosificación , Femenino , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Persona de Mediana Edad , Anciano , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Estudios Prospectivos , Carboplatino/efectos adversos , Carboplatino/administración & dosificación , Antieméticos/uso terapéutico , Antieméticos/administración & dosificación , Neoplasias Torácicas/tratamiento farmacológico , Neoplasias Torácicas/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Japón , Quimioterapia Combinada
4.
Front Physiol ; 14: 1040425, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776965

RESUMEN

Pulse rate variability (PRV), derived from Laser Doppler flowmetry (LDF) or photoplethysmography, has recently become widely used for sleep state assessment, although it cannot identify all the sleep stages. Peripheral blood flow (BF), also estimated by LDF, may be modulated by sleep stages; however, few studies have explored its potential for assessing sleep state. Thus, we aimed to investigate whether peripheral BF could provide information about sleep stages, and thus improve sleep state assessment. We performed electrocardiography and simultaneously recorded BF signals by LDF from the right-index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of polysomnographic recording. Time- and frequency-domain parameters of peripheral BF, and time-domain, frequency-domain, and non-linear indices of PRV and heart rate variability (HRV) were calculated. Finger-BF parameters in the time and frequency domains provided information about different sleep stages, some of which (such as the difference between N1 and rapid eye movement sleep) were not revealed by finger-PRV. In addition, finger-PRV patterns and HRV patterns were similar for most parameters. Further, both finger- and ear-BF results showed 0.2-0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation of respiration within this frequency band. These results showed that peripheral BF could provide information for different sleep stages, some of which was complementary to the information provided by PRV. Furthermore, the combination of peripheral BF and PRV may be more advantageous than HRV alone in assessing sleep states and related autonomic nervous activity.

5.
Anticancer Res ; 43(2): 725-732, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36697059

RESUMEN

BACKGROUND/AIM: Osimertinib is the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The present study aimed to determine the previously unclarified association of osimertinib plasma trough concentrations with efficacy, adverse events, and genetic polymorphisms in Japanese patients with NSCLC harboring EGFR mutations. PATIENTS AND METHODS: In this prospective study, blood samples of 25 patients who received osimertinib were collected to measure plasma osimertinib concentrations and to genotypically characterize ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2 polymorphisms. Plasma osimertinib concentrations were analyzed using validated multiple reaction monitoring mode-based liquid chromatography-tandem mass spectrometry. Osimertinib concentration necessary to achieve optimal median progression-free survival (PFS) was determined using receiver operating characteristic curve analysis. PFS and overall survival were analyzed using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Plasma osimertinib concentrations between different patient groups were compared using the Mann-Whitney U-test. RESULTS: Patients were divided into high and low concentration groups based on a plasma osimertinib cut-off concentration of 211 ng/ml. Median PFS was longer in the high trough concentration group than that in the low trough concentration group (46.3 vs. 16.8 months, p=0.029). Plasma osimertinib concentrations adjusted for dose and body weight did not differ between the patients with and without variant polymorphisms. CONCLUSION: Monitoring plasma trough concentrations during maintenance might improve osimertinib treatment efficacy in patients with NSCLC harboring EGFR mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Estudios Prospectivos , Pueblos del Este de Asia , Inhibidores de Proteínas Quinasas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Mutación , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Adenosina Trifosfato
6.
Anticancer Res ; 43(3): 1301-1307, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36854494

RESUMEN

BACKGROUND/AIM: Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. RESULTS: A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. CONCLUSION: The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.


Asunto(s)
Antieméticos , Neoplasias Torácicas , Humanos , Antieméticos/uso terapéutico , Mirtazapina/uso terapéutico , Platino (Metal) , Carboplatino , Estudios Retrospectivos , Serotonina , Náusea/inducido químicamente , Náusea/prevención & control , Vómitos/inducido químicamente , Vómitos/prevención & control
7.
Biol Pharm Bull ; 35(4): 494-502, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22466552

RESUMEN

Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.


Asunto(s)
Antiinflamatorios/uso terapéutico , Neumonía/tratamiento farmacológico , Enfisema Pulmonar/tratamiento farmacológico , Tiazoles/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Elastasa Pancreática , Neumonía/inducido químicamente , Neumonía/patología , Neumonía/fisiopatología , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatología , Conejos
8.
Mol Clin Oncol ; 16(4): 76, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35251627

RESUMEN

Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m2) and VNR (25 mg/m2) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m2 CDDP (87.2%) and 172 mg/m2 VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity.

9.
Mol Clin Oncol ; 16(4): 91, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35251642

RESUMEN

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents.

10.
Mol Clin Oncol ; 14(6): 116, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33903822

RESUMEN

Due to the increasing complexity of cancer chemotherapy and its associated supportive care, the role of clinical pharmacists in cancer chemotherapy is becoming increasingly more important. The present study evaluated the clinical interventions of a single pharmacist on the adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy. A single-center, retrospective study was conducted at the 614-bed, tertiary care Gifu University Hospital. Hospitalized patients with thoracic cancer who received cancer chemotherapy in the respiratory medicine ward between April 2013 and May 2014 were enrolled. One of the two clinical pharmacists in charge was based in the respiratory medicine ward and implemented pharmaceutical care for the patients, including management of adverse events. Patient data were recorded in the electronic medical chart and retrospectively analyzed. A total of 445 patients with thoracic cancer received cancer chemotherapy in the respiratory medicine ward. A total of 152 interventions (101 patients) were performed by the clinical pharmacist prior to the administration of cancer chemotherapy, half of which comprised the addition of drugs to prevent adverse events. A total of 190 patients (39.4%) experienced grade ≥2 non-hematological or grade ≥3 hematological adverse events associated with cancer chemotherapy, and 223 medical interventions for relief of adverse events lowered the incidence of grade ≥2 non-hematological or grade ≥3 hematological adverse events to 17.8%. Of these, 45.3 and 7.5% of medical interventions for non-hematological and hematological adverse events, respectively, were implemented based on the pharmacist's recommendations. These findings revealed the marked contribution of a single clinical pharmacist in the respiratory medicine ward to the prevention and relief of adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy.

11.
Anticancer Res ; 41(3): 1615-1620, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788757

RESUMEN

BACKGROUND/AIM: We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR). PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy. RESULTS: A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132). CONCLUSION: Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.


Asunto(s)
Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Neutropenia Febril/prevención & control , Filgrastim/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Neutropenia Febril/epidemiología , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/mortalidad
12.
Jpn J Clin Oncol ; 40(3): 263-6, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19897850

RESUMEN

We report a case of gefitinib-induced bilateral upper urinary tract bleeding in an 82-year-old woman administered the drug daily for advanced non-small cell adenocarcinoma of the lung (T4N3M0). Hematuria is an uncommon adverse effect of gefitinib, and in most cases, the bleeding site is unknown. On the 44th day of oral gefitinib administration, the patient noted asymptomatic macroscopic bloody urine. Cystoscopy revealed bleeding from the bilateral ureteric orifices without hemorrhagic inflammation of the bladder. One week later, she was admitted complaining of severe abdominal pain, and her condition was found to be complicated by liver damage and renal dysfunction. We stopped gefitinib administration and started hydration and diuresis. Renal function and urine output soon recovered, and at the request of the patient, we restarted gefitinib, administering it every other day, which was sufficient to maintain antitumor activity and stabilize the disease. On the 41st day after restarting gefitinib, hematuria and proteinuria reappeared. We therefore stopped the gefitinib, and the patient was followed with supportive care. The patient's autopsy findings denied organic urologic diseases. Instead, the reproducibility of the hematuria from the upper urinary system strongly suggests an unexpected gefitinib-related adverse effect.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/efectos adversos , Hematuria/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/efectos adversos , Sistema Urinario/efectos de los fármacos , Adenocarcinoma/patología , Anciano de 80 o más Años , Receptores ErbB/antagonistas & inhibidores , Femenino , Gefitinib , Hematuria/patología , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Resultado del Tratamiento , Sistema Urinario/patología
13.
Jpn J Clin Oncol ; 40(7): 658-62, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20395244

RESUMEN

OBJECTIVE: When treating lung cancer, pneumocystic pneumonia is a life-threatening complication seen during chemotherapy. Polymerase chain reaction is used to detect its cause, Pneumocystis jirovecii, but polymerase chain reaction positives without pneumocystic pneumonia are sometimes seen. The purpose of this study was to assess the frequency of pneumocystic pneumonia during cancer treatment. METHODS: Fifty induced sputum specimens and 4 bronchoalveolar lavage specimens collected from 50 patients with acute respiratory symptoms during anticancer therapy were retrospectively studied after classifying the patients into lung cancer (n = 29) and solid tumor (n = 21) groups. All of the patients in both groups had an interstitial shadow suspected of being pneumocystic pneumonia, and all had polymerase chain reaction tests. RESULTS: Eleven of the 54 specimens were polymerase chain reaction positive, and 1 patient was clinically diagnosed with pneumocystic pneumonia. The incidence of polymerase chain reaction positivity in the lung cancer group was significantly higher than in the solid tumor group (31 vs. 5%; P = 0.03), and the incidence of subclinical pneumocystic pneumonia (29 vs. 5%; P = 0.059) also tended to be higher in that group. There were no significant biochemical differences between the two groups, irrespective of the polymerase chain reaction results. Among polymerase chain reaction-positive patients in the lung cancer group, the cumulative dose of corticosteroid administration tended to be higher than among the polymerase chain reaction-negative patients (P = 0.09). Following the polymerase chain reaction tests, nearly all polymerase chain reaction-positive patients without pneumocystic pneumonia received antipneumocystic agents, and none developed pneumocystic pneumonia. CONCLUSIONS: Our findings suggest polymerase chain reaction positivity for P. jirovecii will be detected in a fraction of lung cancer patients. Although it is difficult to predict the need for administration of pneumocystic pneumonia treatment to subclinical pneumocystic pneumonia based on polymerase chain reaction and biochemical results, polymerase chain reaction-positive patients should be followed-up with antipneumocystic agents to ensure they are not at an early stage of pneumocystic pneumonia.


Asunto(s)
Neoplasias Pulmonares/complicaciones , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/epidemiología , Reacción en Cadena de la Polimerasa , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pneumocystis carinii/genética , Neumonía por Pneumocystis/complicaciones , Neumonía por Pneumocystis/diagnóstico
14.
Respiration ; 80(1): 24-31, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19864882

RESUMEN

BACKGROUND: Bronchial artery (BA) embolization (BAE) is recommended as a minimally invasive therapy for hemoptysis, though some patients recover after only conservative treatment. OBJECTIVES: The purpose of our study was to assess the characteristics of BAs using multidetector row computed tomography (MDCT) and identify BAs requiring BAE without BA angiography (BAG). METHODS: We retrospectively studied 41 patients and classified the visualized BAs into groups based on their BAE and bleeding statuses. Patients presenting with massive hemoptysis requiring emergency BAE were excluded. Patients presenting with persistent hemoptysis that was resistant to conservative treatment received BAE. Radiologists measured BA diameters at the ostium, bronchial bifurcation and pulmonary hilum, and also evaluated the degree of vascularization. RESULTS: MDCT enabled visualization of 102 ostia and 96 traceable BAs. Among the participating patients, 13 had at least one ectopic origin. We obtained a good correlation between BAG and MDCT diameters (r = 0.709, p < 0.001). The diameters of BAs responsible for bleeding and receiving BAE were apparently larger in each measured segment than those that were not (p < 0.05). Moreover, the diameters of arteries receiving BAE remained largely unchanged from the origin to the hilum and through the mediastinum. BAs with low MDCT scores were significantly less likely to required BAE than those with high scores (p = 0.004), and in multiple logistic regression analysis, ostium diameter and bleeding status were independent predictive factors for BAE. CONCLUSIONS: Evaluation of BAs on MDCT could be useful for identifying the anatomical characteristics of bleeding-related BAs and determining whether BAE is indicated or whether conservative treatment is sufficient.


Asunto(s)
Arterias Bronquiales , Embolización Terapéutica , Hemoptisis/diagnóstico por imagen , Hemoptisis/terapia , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Hemoptisis/etiología , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Resultado del Tratamiento
15.
J Asthma ; 46(2): 142-6, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19253119

RESUMEN

The purpose of this study was to assess the effect on bone mineral density (BMD) of systemic corticosteroid (SCS) intermittently administered for rescue from asthmatic exacerbation. Through digital image processing and calculation of four other indices, BMD was compared in groups of asthmatic patients receiving inhaled corticosteroid (ICS) alone or ICS plus intermittent SCS. We defined SCS as intermittent administration of the equivalent of 1 mg/day prednisolone in the management of asthma exacerbations during the previous 1 year. Serum NTX, a bone resorption marker, was significantly higher (p = 0.02) in the SCS group than the ICS group. SCS had no effect on BMD, although the frequency of patients at "high-risk" for osteoporosis according to the Female Osteoporosis Self-assessment Tool for Asia (FOSTA) tended to be higher in the SCS group (35%) than in the ICS (28%) or control (10%) group. Because patients in the ICS group already had impaired respiratory function due to repeated asthma exacerbations, it was difficult to determine whether it was asthma itself or SCS that is the risk factor for osteoporosis. In addition, the response of biochemical markers of bone turnover to intermittent SCS remains unclear and likely differs from that elicited by high-dose, short-term, or continuous SCS. That said, relatively low-dose intermittent administration of SCS raised levels of bone resorption markers, which likely reflects altered bone metabolism. Taken together, these findings suggest that, without consideration of its effects on bone, SCS administration should be avoided.


Asunto(s)
Corticoesteroides/administración & dosificación , Corticoesteroides/farmacología , Asma/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Adolescente , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Agonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Asma/complicaciones , Asma/fisiopatología , Estatura/efectos de los fármacos , Huesos/metabolismo , Colágeno Tipo I/sangre , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Péptidos/sangre , Factores de Riesgo , Adulto Joven
16.
Nihon Kokyuki Gakkai Zasshi ; 47(11): 1057-62, 2009 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-19994605

RESUMEN

We report a rare case of sarcoidosis-lymphoma syndrome with vertebral bone destruction. A 63-year-old woman was previously diagnosed as sarcoidosis by supraclavicular lymph node biopsy, and came to our hospital complaining of back pain. Both serum angiotensin-converting enzyme and lysozyme level had been continuously elevated. Magnetic resonance imaging revealed lumbar vertebral bone destruction. Histopathologic examination of lumbar vertebral tumor obtained by CT-guided biopsy revealed non-caseating epithelioid granuloma with CD 68 (+), AE1/AE3 (-), and no malignant cells. She was admitted to our hospital again for dyspnea and pancytopenia. We diagnosed active sarcoidosis and administered oral 30mg prednisolone daily. One month later, prednisolone became ineffective. Flow cytometry of tumor cells obtained from the gastric ulcer floor showed CD 5 (+), CD 20 (+), K chain monoclonality and we diagnosed B-cell non Hodgkin's lymphoma. She was treated by eight cycles of CHOP plus rituximab chemotherapy and achieved complete response. FDG uptake of the entire body decreased, whereas MRI revealed residual mass in the vertebrae. Sarcoidosis had been diagnosed for two and half years before lymphoma developed. Bone destruction is very rare and sarcoidosis is rarely the cause. This is quite an unusual case presenting histologically proved epithelioid granuloma and vertebral destruction in sarcoidosis-lymphoma syndrome.


Asunto(s)
Linfoma/complicaciones , Linfoma/patología , Sarcoidosis/complicaciones , Sarcoidosis/patología , Columna Vertebral/patología , Femenino , Humanos , Persona de Mediana Edad , Síndrome
17.
Respir Med Case Rep ; 28: 100871, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31198679

RESUMEN

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction.

18.
Lung Cancer ; 134: 1-6, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31319966

RESUMEN

OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Afatinib is a second-generation EGFR-TKI with excellent therapeutic effects. However, severe diarrhea and skin disorders are observed at high frequencies, often leading to treatment interruption because of low quality of life (QOL). The relationship between individual variations and the onset of these side effects remains to be elucidated. This study aimed to reveal the association among these side effects, pharmacokinetics, and related genetic polymorphisms. MATERIALS AND METHODS: In total, 33 patients were recruited between July 2014 and June 2017. Afatinib plasma concentrations were measured at day 9 when the concentrations reached a steady state (early phase) and when the prescription dose was stable for more than 1 month (stable phase). We analyzed single nucleotide polymorphisms in the genes ATP-binding cassette sub-family B member 1 (ABCB1), ABCG2, and flavin-containing monooxygenase 3. RESULTS: The incidences of both diarrhea and acneiform eruption were greater than 80%. Afatinib plasma concentration and the severity of diarrhea in the early phase were correlated. Pharmacokinetics-related genetic polymorphisms influenced the severity of diarrhea. Particularly, the afatinib plasma concentration was higher and diarrhea was more severe in patients carrying the A allele of ABCG2 C421A. Onset of side effects, genetic polymorphisms, and diarrhea in the maintenance phase or acneiform eruption in the early or maintenance phases were not correlated. The severity of diarrhea is influenced by drug plasma concentrations in the early phase and genetic polymorphisms related to afatinib pharmacokinetics. CONCLUSION: Particular genetic polymorphisms can be screened before afatinib administration and the dose adapted to individual patients can be controlled, leading to reduced side effects, improved QOL, and better patient compliance to maintain the therapeutic effects.


Asunto(s)
Afatinib/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Variantes Farmacogenómicas , Polimorfismo Genético , Inhibidores de Proteínas Quinasas/efectos adversos , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Afatinib/farmacocinética , Anciano , Alelos , Sustitución de Aminoácidos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Diarrea/diagnóstico , Diarrea/etiología , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Genotipo , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacocinética , Índice de Severidad de la Enfermedad
19.
Nihon Kokyuki Gakkai Zasshi ; 46(4): 314-8, 2008 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-18516996

RESUMEN

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.


Asunto(s)
Carcinoma de Células Pequeñas/complicaciones , Proteínas ELAV/inmunología , Hipoventilación/etiología , Neoplasias Pulmonares/complicaciones , Polineuropatía Paraneoplásica/complicaciones , Anciano , Anticuerpos/análisis , Humanos , Masculino
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