RESUMO
BACKGROUND: Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose. METHODS: T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled. RESULTS: We investigated 13 patients (5 definitive and 8 possible LM cases). In two of the five definitive cases with T790M in and outside the central nervous system (CNS), osimertinib was effective for both lesions, with cerebrospinal fluid (CSF) clearance of cancer cells and sensitive/T790M mutations. In three definitive cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive mutations in the CSF persisted after osimertinib initiation. The median progression-free survival of all 13 patients was 7.2 months. Osimertinib was generally well-tolerated despite poor performance status, but interstitial lung disease (grade 2) was confirmed in one patient. Based on 25 samples from 13 patients, the osimertinib CSF penetration rate was 2.5±0.3%. CONCLUSIONS: Osimertinib 80 mg is a useful therapeutic option for refractory LM after classical EGFR-TKI failure. It appears more effective in CSF T790M-positive cases.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Acrilamidas , Idoso , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/líquido cefalorraquidiano , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/genética , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/genética , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Piperazinas/efeitos adversos , Piperazinas/líquido cefalorraquidiano , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/líquido cefalorraquidiano , Resultado do TratamentoRESUMO
Epithelioid inflammatory myofibroblastic sarcoma is a variant of inflammatory myofibroblastic tumor with aggressive clinical course associated with RANBP2-ALK fusion. The present report describes a case of a 22-year-old Japanese man with a pelvic mesenchymal neoplasm. The feature of the neoplasms, including epithelioid morphology, anaplastic lymphoma kinase staining on the nuclear membrane, and results from the reverse transcriptase-polymerase chain reaction, led to diagnosis of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion. Despite two surgical excision procedures, local recurrence rapidly occurred, and the tumor developed resistance to conventional chemotherapy with doxorubicin. Subsequent administration of crizotinib, an oral anaplastic lymphoma kinase inhibitor, resulted in tumor shrinkage. Distinguishing epithelioid inflammatory myofibroblastic sarcoma from conventional inflammatory myofibroblastic tumor is important, and crizotinib is a promising treatment for this aggressive tumor.
Assuntos
Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Tecido Muscular/tratamento farmacológico , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Crizotinibe , Humanos , Inflamação , Masculino , Recidiva Local de Neoplasia/genética , Neoplasias de Tecido Muscular/genética , Neoplasias de Tecido Muscular/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma/genética , Sarcoma/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Neo-adjuvant chemotherapy(NAC)may affect hormone receptor(HR)and human epidermal growth factor receptor 2(HER2)status in breast cancer patients. However, the correlation between recurrence rates and this status change remains unclear. METHODS: We evaluated 70 consecutive breast cancer patients receiving NAC with anthracyclines and taxanes, with or without trastuzumab, between January 2005 and May 2012. Pre-treatment core needle biopsy samples and specimens obtained after surgery were tested to determine HR and HER2 status. The relationship between HR and HER2 status changes and recurrence rates was then assessed. RESULTS: Pathological complete response(pCR)was observed in 13 cases and non-pCR was observed in 57 cases. Of the non-pCR cases, HR-positive status changed to HR-negative status in 6.3% of patients, but a change from negativity to positivity was not observed. HER2-positive status changed to HER2-negative status in 48.0% of patients, and a change from negativity to positivity was observed in 12.5% of cases. The recurrence rate among patients with conversion to a HR-negative status was 0%and that among patients with conversion to a HER2-negative status was 25.0%. CONCLUSION: Recurrence rates were not significantly associated with HR and HER2 status conversion after NAC. Future research is warranted to confirm out results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Humanos , Pessoa de Meia-Idade , Recidiva , Taxoides/administração & dosagem , TrastuzumabRESUMO
In non-small-cell lung cancer, continuous immune-checkpoint inhibitors (ICIs) beyond progression are often used in clinical practice. On the other hand, there is almost no data on whether the concept of continuous ICIs beyond progression can be adopted in small-cell lung cancer (SCLC). We describe the effectiveness of continuous ICIs beyond progression in SCLC. Medical courses of SCLC patients treated with chemo-immunotherapy were retrospectively reviewed at our hospital. The study included 36 patients with a median age of 73 years (range 46-83 years) who introduced chemo-immunotherapy between September 2019 and December 2022. Atezolizumab and durvalumab in combination with platinum plus etoposide were administered in 24 and 12 patients, respectively. The overall response rate was 67% and the disease control rate was 86%. The median progression-free survival and time to treatment failure (TTF) were 5.1 and 10.3 months, respectively. The median cycle of ICIs was 5 (range 1-42). The median overall survival was 13.6 months. ICIs were administered beyond progression in 14 (39%) patients: five were treated again with chemo-immunotherapy and local ablative radiotherapy, four with local ablative radiotherapy and continuous ICIs, three with chemo-immunotherapy, and two with continuous ICIs alone. TTF exceeded 12 months in 12 (86%) of the 14 cases, six of which were still on ICIs. Adverse events ≥grade 3 were observed in 21 (58%) patients. A notable TTF suggested a benefit of continuous ICIs beyond progression. The concept could be suitably adopted and provide a favorable prognosis in selected cases of SCLC that were previously regarded as an aggressive malignancy.
Assuntos
Imunoterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Imunoterapia/métodos , Estudos Retrospectivos , Progressão da Doença , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologiaRESUMO
We report a case of a 32-year-old woman with a septic pulmonary embolism-related implanted central venous port. She was treated with S-1/cisplatin(CDDP)chemotherapy for recurrent gastric cancer. Her disease was progressive after five courses of S-1/CDDP combination therapy. Because of peritonitis carcinomatosa, her oral intake was poor, so we placed an implanted central venous port in her right subclavian vein. We administered 5-FU/Leucovorin/paclitaxel combination therapy and total parenteral nutrition from the port. Chemotherapy was effective, so we stopped total parenteral nutrition after one month. Two months later, multiple nodular shadows appeared in her left lung fields without apparent symptoms. Because we suspected septic pulmonary embolism related to the venous port, we removed the venous port promptly and administered antibiotics with a broad spectrum. Pulmonary shadows disappeared immediately, and no recurrence was observed afterward.
Assuntos
Cateterismo Venoso Central , Cateteres de Demora , Embolia Pulmonar/etiologia , Sepse/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Ácido Oxônico/administração & dosagem , Sepse/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagemRESUMO
BACKGROUND: Cisplatin, a first-generation platinum agent, is used for managing various cancers and is associated with dose-dependent side effects of hearing impairment and tinnitus. However, the safety of high-dose cisplatin in hearing impairment, has not been fully investigated in Japan. METHODS: We performed pure-tone threshold audiometry before and every 3-4 weeks after chemotherapy for patients receiving cisplatin-containing chemotherapy between April 2015 and October 2017 at Kobe Minimally Invasive Cancer Center. Hearing impairment was evaluated prospectively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: We enrolled 100 patients and analyzed 96 patients for whom post-chemotherapy audiometry could be performed. The median patient age was 65 years, and most patients were male (75). The cancer types were as follows: esophageal, 36; head and neck, 35; lung, 23; and gastric, 2. Cisplatin monotherapy and combination therapy were administered to 33 and 63 patients, respectively. A single cisplatin dose was 60-100 mg/m2 ; the median number of doses and total dose were 3 and 240 mg/m2 , respectively. Additionally, 78 and 18 patients were treated with concurrent chemoradiotherapy and chemotherapy alone, respectively. Twenty-seven patients had grade 2 or higher hearing impairment. Furthermore, the prevalence was significantly higher in patients receiving a total dose of ≥300 mg/m2 . Twenty and 32 patients were aware of deafness and tinnitus, respectively. CONCLUSION: No patient discontinued treatment owing to hearing impairment. The total cisplatin dose was considered related to post-treatment hearing impairment frequency in Japanese patients. However, routine audiometric monitoring is recommended during high-dose cisplatin-based chemotherapy.
Assuntos
Antineoplásicos , Cisplatino , Perda Auditiva , Neoplasias , Ototoxicidade , Zumbido , Idoso , Feminino , Humanos , Masculino , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , População do Leste Asiático , Perda Auditiva/induzido quimicamente , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Neoplasias/tratamento farmacológico , Ototoxicidade/diagnóstico , Ototoxicidade/tratamento farmacológico , Fatores de Risco , Zumbido/induzido quimicamente , Zumbido/diagnóstico , Zumbido/epidemiologiaRESUMO
Introduction: Docetaxel plus ramucirumab could be a promising treatment for chemo-naive elderly patients with NSCLC, but high incidence of febrile neutropenia (FN) is a critical concern. We thus adopted a routine primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF) to reduce FN and maximize the efficacy of docetaxel plus ramucirumab in elderly patients. Methods: This is a single arm phase 2 trial for chemo-naive elderly patients (aged ≥75 y) with advanced NSCLC. Docetaxel (60 mg/m2, d 1) plus ramucirumab (10 mg/kg, d 1) with PEG-G-CSF (3.6 mg, d 2) was administered every 3 weeks until progression. The primary end point was overall response rate (ORR) (expected ORR: 35%). Results: Between February 2018 and January 2021, 54 patients were enrolled. Median age was 78 (range: 75-86). A total of 21 (38.9%) partial response, 22 (40.7%) stable disease, nine (16.7%) progressive disease, and two (3.7%) not assessable were confirmed, resulting in ORR of 38.9% (90% confidence interval [CI]: 27.7%-51.0%) and disease control rate of 79.6%. Median progression-free survival and overall survival were 5.2 (95% CI: 4.2-6.9) and 12.7 (95% CI: 10.2-18.9) months, respectively. There were one (1.9%) FN, two (3.7%) bleeding grade greater than or equal to 3, and one (1.9%) treatment-related death (pneumonitis). Pneumonitis occurred in five patients (9.3%). Main adverse events grade greater than or equal to 3 were observed: four (7%) thrombocytopenia; three (5.6%) neutropenia; six (11.1%) hyposodium; five (9.3%) infection; five (9.3%) hypertension; four (7.4%) anorexia; and three (5.6%) oral mucositis. Conclusions: Docetaxel plus ramucirumab with PEG-G-CSF revealed efficacy and safety for chemo-naive elderly patients with NSCLC. Primary prophylactic PEG-G-CSF highly prevented FN.
RESUMO
BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Recent pivotal phase III trials involving direct oral anticoagulant (DOAC) versus low molecular weight heparin have demonstrated the utility of DOACs in Western patients with cancer-associated venous thromboembolism (VTE). However, these trials did not include Japanese patients. This phase II trial evaluated the safety and efficacy of apixaban in Japanese patients with cancer-associated VTE (UMIN000028447). METHOD AND RESULTS: Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. The primary endpoint was the incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. The study was terminated due to safety concerns after enrolling 27 patients. Median age was 71 years; median body weight was 51.3 kg; and major primary tumor sites were the gastrointestinal tract (26%) and lung (19%). During the median follow-up period of 5.4 months, major or CRNM bleeding occurred in in 26% of patients (major, n = 5; CRNM, n = 2; 95% confidence interval, 11-46%). No recurrent VTE or VTE-related death occurred. Estimated overall survival at 6 months was 68%. CONCLUSION: This study demonstrated the excessive bleeding risk of apixaban at the standard dose in Japanese patients with cancer-associated VTE.
Assuntos
Neoplasias , Tromboembolia Venosa , Administração Oral , Idoso , Anticoagulantes , Humanos , Japão/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Pirazóis , Piridonas/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
INTRODUCTION: Alternation of osimertinib and afatinib is a potential approach to overcome osimertinib resistance and to allow complementation of drug efficacy without compromising safety in patients with epidermal growth factor receptor gene (EGFR)-mutated non-small cell lung cancer (NSCLC). METHODS: Treatment-naive patients with stage IV NSCLC harboring an activating EGFR mutation (L858R or exon-19 deletion) were enrolled. Alternating cycles of osimertinib at 80 mg/day for 8 weeks followed by afatinib at 20 mg/day for 8 weeks were administered. The primary end point was 12-month progression-free survival (PFS) probability. RESULTS: Forty-six patients were enrolled and treated with study therapy. The 12-month PFS probability was 70.2% (60% confidence interval [CI], 63.9-75.6%; 95% CI, 54.2-81.5%), which did not meet the primary end point. After a median follow-up time of 25.7 months, the median PFS was 21.3 months (95% CI, 16.3 months-not reached). The overall response rate was 69.6% (95% CI, 54.2-82.3%). The most common treatment-related adverse events (any grade or grade ≥ 3, respectively) were diarrhea (73.9%, 4.3%), rash acneiform (63.0%, 2.2%), and paronychia (52.2%, 0%). Five cases of pneumonitis, two of grade 2 and thres of grade 3, were apparent, all of which developed during osimertinib treatment. Exploratory evaluation of circulating tumor DNA suggested that coexisting TP53 mutations did not influence PFS for the alternating therapy. CONCLUSIONS: Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas/efeitos adversos , Afatinib/efeitos adversos , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Genes erbB-1 , Humanos , Indóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Pirimidinas/efeitos adversosRESUMO
The spread of next-generation sequencing enables clinicians to identify rare oncogene alterations, including MET exon 14 skipping mutation, in clinical practice for NSCLC. Several tyrosine kinase inhibitors for MET exon 14 skipping mutation such as capmatinib and tepotinib have elucidated their effectiveness. Only a few reports have suggested their efficacy against central nervous system lesions, especially leptomeningeal metastases. We here report a case of a patient with NSCLC with MET exon 14 skipping mutation and poor performance status salvaged by marked leptomeningeal metastases response to tepotinib. We further provide measures of plasma/cerebrospinal fluid concentrations of tepotinib and its cerebrospinal fluid penetration rate.
RESUMO
BACKGROUND: Indication for treatment with osimertinib after first/second generation (1/2G) epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance depends on T790M mutation detected by rebiopsy. The aim of our study was to analyze the data on clinical practice at our hospital where histological rebiopsy is actively carried out multiple times. METHODS: We retrospectively reviewed our electronic medical records of EGFR-mutant non-small cell lung cancer (NSCLC) patients to examine clinical rebiopsy situation, T790M detection rate, osimertinib introduction rate and associated outcomes. RESULTS: Among 95 patients with EGFR-mutant NSCLC, 72 patients received 1/2G EGFR-TKIs. Of 60 with progressive disease on 1/2G EGFR-TKIs, 50 (83%) underwent rebiopsy. T790M was detected in 40 (80%) of 50, resulting in a 79% osimertinib introduction rate, as one patient refused osimertinib. T790M was detected by first rebiopsy in 18 (36%) of 50 patients, and by second or subsequent rebiopsy in 22 (44%). Median time to treatment failure of T790M-positive patients at first rebiopsy was 22.6 (95% confidence interval [CI]: 10.2-32.8) months, and those at multiple repeated rebiopsy was 20.9 (95% CI: 8.6-not reached) months (p = 0.64). Median overall survival (OS) in osimertinib introduced group was 92.5 (95% CI: 62.9-not reached), while in nonosimertinib median OS was 39.0 months (95% CI: 22.2-not reached) (p = 0.04). CONCLUSIONS: T790M detection rate was increased by multiple repeated rebiopsy, achieving a higher osimertinib introduction rate. This higher introduction rate could contribute to better prognosis of EGFR-mutant NSCLC patients.
Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Biópsia/métodos , Receptores ErbB/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/farmacologia , Receptores ErbB/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Estudos RetrospectivosRESUMO
BACKGROUND: Although rare, cytomegalovirus (CMV) reactivation can be lethal in patients with cancer. However, the criteria for the prevention of cytomegalovirus reactivation during cancer treatment are unclear. This study aimed to identify factors associated with CMV reactivation in patients with esophageal cancer who were receiving chemoradiotherapy. METHODS: This retrospective study included esophageal cancer patients receiving definitive or palliative chemoradiotherapy during April 2013-March 2020. Patients with fever during chemoradiotherapy underwent a systemic work-up to detect the primary focus of infection, and CMV antigenemia was assessed in cases of unidentifiable infection. RESULTS: Among 132 patients (80.3% male, median age 69 years [range, 39-86 years]), 124 received 5-fluorouracil plus cisplatin and 8 received oxaliplatin-5-fluorouracil-levofolinate chemotherapy. Overall, 19 patients had CMV reactivation, 37 had other infections, and 76 had no identified infection (groups 1, 2, and 3, respectively). Median minimum lymphocyte counts were 81.0/µl (interquartile range: 52.0-144.0/µl), 120.0/µl (81.0-162.5/µl), and 185.5/µl (120.5-328.0/µl) in groups 1, 2, and 3, respectively, with counts being significantly lower in groups 1 and 2 than in group 3 (p < 0.001). In multiple logistic regression analysis, the minimum lymphocyte count was associated with CMV reactivation (odds ratio 0.983, 95% confidence interval: 0.973-0.994, p = 0.002). CONCLUSION: CMV reactivation is not rare in patients with esophageal cancer who were receiving chemoradiotherapy and is associated with the minimum lymphocyte counts. CMV reactivation should be considered during differential diagnosis for patients with a severe decline in lymphocyte counts when receiving chemoradiotherapy.
Assuntos
Quimiorradioterapia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/fisiologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/virologia , Ativação Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/imunologia , Feminino , Humanos , Contagem de Linfócitos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
Case 1 was a 53-year-old man with a past history of chronic pancreatitis, diabetes mellitus and left upper lobectomy for lung cancer, 3 years previously. He was admitted with fever and an abnormal consolidative shadow in the left upper lung field of his chest X-ray film. Aspergillus fumigatus and Aspergillus niger were detected in his sputum and bronchial washing. Case 2 was a 60-year-old man, in whom left upper lobectomy had been performed for lung cancer 7 years previously. He was admitted with cough and fever. His chest X-ray film showed consolidation with a cavitary lesion in the left upper lung field. Aspergillus fumigatus was detected in his bronchial washing. Each case was treated successfully with a combination of antifungal agents.
Assuntos
Antifúngicos/administração & dosagem , Aspergilose Pulmonar/tratamento farmacológico , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 69-year-old man was referred to our hospital with fever. Interstitial pneumonia and right pleural effusion were noted with elevated MPO-ANCA. Video-assisted thoracoscopic lung biopsy was performed and UIP -like histology was obtained. His symptoms and chest X-ray finding improved with administration of prednisolone and cyclosporine, but ten months later diplopia appeared. He had right abducens palsy and impaired perception in the first right trigeminal branch area, and we diagnosed mononeuritis multiplex due to microscopic polyangiitis.
Assuntos
Doenças do Nervo Abducente/complicações , Doenças Pulmonares Intersticiais/complicações , Poliangiite Microscópica/complicações , Paralisia/complicações , Idoso , Humanos , MasculinoRESUMO
The patient was given Sai-rei-to, adenosine triphosphate disodium and Mecobalamin on a diagnosis of sudden deafness. Forty days later, exertional dyspnea and cough appeared. He was given a diagnosis of bacterial pneumonia and was treated with several antibiotics. His respiratory state gradually worsened and he was refered to our hospital. His chest computed tomography scan showed ground-glass opacity, with consolidation, and laboratory data showed high values of white blood cell and liver dysfunction. After halting all medicines, he recovered. Because the lymphocyte stimulation test was positive for Sai-rei-to and he was still well after taking adenosine triphosphate disodium and Mecobalamin, we diagnosed drug-induced pneumonitis caused by Sai-rei-to.
Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Pneumonia/induzido quimicamente , Adulto , Perda Auditiva Súbita/tratamento farmacológico , Humanos , MasculinoRESUMO
A 23-year-old man had been treated for repeated pneumonia from the age of 16. After a diagnosis of eosinophilic pneumonia at the age of 17, he had been given antibiotics and steroids. At the age of 23, he was referred to our hospital. Although he improved rapidly in response to antibiotic medication, his chest X-ray shadows did not improve. Video-assisted thoracoscopic lung biopsy was performed. Fibrosis and invasion of inflammatory cells were seen on the air duct walls and foreign bodies that were thought to be food residue were detected. A diagnosis of chronic aspiration pneumonia was made pathologically. A brain stem tumor was detected on his brain magnetic resonance imaging, which was thought to be the cause of his mis-swallowing.
Assuntos
Neoplasias do Tronco Encefálico/complicações , Pneumonia Aspirativa/etiologia , Adulto , Doença Crônica , Humanos , MasculinoRESUMO
A 56-year-old man and a 53-year-old woman with cough, sputum and dyspnea were admitted in the summer. High-resolution computed tomographic findings of the chest showed centrilobular branching opacities like diffuse panbronchiolitis with ground glass opacities. Both cases showed hypoxia, a high titer of serum anti-Tricosporon antibody and exacerbation in their own homes. Video-assisted thoracoscopic lung biopsy revealed granuloma in the bronchioles area. We diagnosed summer type hypersensitivity pneumonitis and this condition improved in response to antigen isolation and steroids. Remarkable changes in the bronchioles were characteristic in the two cases.
Assuntos
Alveolite Alérgica Extrínseca/patologia , Bronquíolos/patologia , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estações do Ano , Tomografia Computadorizada por Raios XRESUMO
A 77-year-old man underwent radiotherapy for the squamous cell carcinoma of the right lung. Two months after the 60Gy/30fr irradiation was completed, he complained of dyspnea and his chest X-ray showed ground glass opacities and reticular shadows in both lung fields. Severe radiation pneumonitis was diagnosed. Two grams of methylprednisolone did not improve his symptoms and on the next day his hypoxemia worsened. We then tried plasma exchange because of his critical status. His respiratory status improved rapidly after plasma exchange and his chest X-ray showed remarkable improvement 10 days later. We think this case suggests the effectiveness of plasma exchange for severe radiation pneumonitis.
Assuntos
Troca Plasmática , Pneumonite por Radiação/terapia , Idoso , Carcinoma de Células Escamosas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , MasculinoRESUMO
PURPOSE: This open-label, phase I, dose-escalation part of a phase I/II study evaluated the safety, pharmacokinetics, and preliminary efficacy of nintedanib, a triple angiokinase inhibitor, combined with pemetrexed in Japanese patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. METHODS: A fixed dose of pemetrexed (500 mg/m(2) iv) was administered on Day 1 of each 21-day cycle followed by oral nintedanib twice daily (bid) on days 2-21, starting at 100 mg bid and escalating to 200 mg bid in 50-mg intervals, using a standard 3 + 3 design. After ≥4 cycles of combination therapy, patients could continue nintedanib monotherapy until disease progression or undue adverse events (AEs). Primary endpoints were maximum tolerated dose (MTD), defined as the highest dose at which the incidence of dose-limiting toxicities (DLTs) was <33.3 % during the first treatment course, and AEs (CTCAE v3.0). DLTs were primarily defined as grade ≥3 non-hematologic or grade 4 hematologic AEs. RESULTS: Eighteen patients were included in the analysis. DLTs were experienced by 2/9 patients receiving 200 mg bid, 1/6 receiving 150 mg bid, and 0/3 receiving the lowest dose. The MTD of nintedanib plus pemetrexed was 200 mg bid. The most common drug-related AEs were elevated liver enzymes and gastrointestinal AEs. Two patients achieved partial response, and 10 had stable disease. CONCLUSIONS: Nintedanib plus pemetrexed had a manageable safety profile and showed promising signs of efficacy in previously treated Japanese patients with advanced NSCLC. As in Caucasian patients, the MTD of nintedanib was 200 mg bid. Clinical trial information NCT00979576.