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2.
Life Sci ; 240: 117093, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760100

RESUMO

Immunotherapy with immune checkpoint inhibitors, such as anti-PD-1 drugs, is an area in increasing development for its efficacy and advantages in the treatment of advanced metastatic melanoma. In fact, immunotherapy has been the target of several and recent studies in different types of cancer, namely in melanoma, a globally growing threat. Contributing to the increasing incidence of this cancer is climate change, particularly global warming of the past century, which has increased the tendency to spend more time outdoors and, consequently, exposure to sunlight and ultraviolet radiation. Among the most relevant risk factors for melanoma is the increase in ultraviolet radiation due to ozone layer depletion, one of the main factors responsible for the incidence of new cases. Anti-PD-1 agents like Nivolumab and Pembrolizumab allow a more effective treatment, enhancing the duration of the responses to therapy and prolonging the survival of the patient. However, recent studies about safety and tolerability have stated that, although these drugs present less adverse effects and toxicity, they may lead to specific autoimmune-mediated adverse events. Overall, immunotherapy with anti-PD-1 agents represents a highly promising area in the treatment of some types of cancer such as melanoma.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Metástase Neoplásica , Nivolumabe/uso terapêutico
4.
J Oncol Pharm Pract ; 26(1): 224-227, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30880569

RESUMO

PURPOSE: Nivolumab is a fully human IgG4 programmed death 1 immune checkpoint inhibitor (ICI) antibody that has anti-tumor activity by selectively blocking the interaction of the programmed death 1 receptor with its two known programmed death ligands PD-L1 and PD-L2. In doing so, this immune checkpoint inhibitor removes the negative signal stifling T cell activation and proliferation within the tumor microenvironment and demonstrates favorable antitumor activity. CASE REPORT: We report an interesting case of immune checkpoint inhibitor-induced primary hypothyroidism with associated hypothyroid myopathy in a young patient with surgically resected stage IIIB melanoma receiving adjuvant nivolumab. He presented 12 weeks into therapy with severe myalgias, arthralgias, and intermittent disequilibrium of unclear etiology. Laboratory evaluation demonstrated a significant elevation in thyroid stimulating hormone and creatine kinase with an undetectable free T4 with standard laboratory measurement. With thyroid hormone replacement therapy alone, he had rapid improvement in his musculoskeletal symptoms and laboratory parameters over a three-week period. DISCUSSION: This case emphasizes the serious nature of endocrine immune-related adverse events in patients receiving immune checkpoint inhibitors. Additionally, it highlights that unlike most other immune-related adverse events, endocrine immune-related adverse events can generally be managed with adequate hormone replacement alone with swift improvements in symptoms. This allows patients to continue immune checkpoint inhibitors safely without immunosuppression which may dampen the anti-tumor activity of these agents. CONCLUSION: This case highlights the importance of early recognition and the appropriate management of endocrine immune-related adverse events to maximize patient safety and good outcomes.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Hipotireoidismo/induzido quimicamente , Doenças Musculares/induzido quimicamente , Nivolumabe/efeitos adversos , Adulto , Humanos , Masculino , Melanoma/tratamento farmacológico
5.
J Oncol Pharm Pract ; 26(1): 236-239, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30955467

RESUMO

BACKGROUND: Immune checkpoint inhibitors are medications that activate anti-tumor responses by disrupting the inhibitory signaling to T cells. Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1 (PD-1). Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. CASE: A 49-year-old male with a body mass index of 26.4 kg/m2, a history of Dandy-Walker syndrome and epilepsy, and no personal or family history of diabetes underwent left radical nephrectomy and retroperitoneal lymph node dissection for stage IV metastatic renal cell carcinoma (metastases to lungs). He received first-line sunitinib treatment for three months. He developed new hepatic metastasis, and a second-line treatment with nivolumab 3 mg/kg every two weeks was introduced. At 10 months of nivolumab, before the 22nd infusion, the patient suddenly complained of severe asthenia, somnolence, weight loss, polydipsia, and polyuria. Laboratory tests revealed potassium 4.2 mmol/L, sodium 138 mmol/L, bicarbonate 17.8 mmol/L, blood glucose 801 mg/dL, and arterial blood pH 7.27. He was diagnosed with diabetic ketoacidosis. Hemoglobin A1C was 10.9%. C-peptide was so low as 0.24. Glutamic acid decarboxylase autoantibodies, insulin autoantibodies and islet cell antibodies were all negative. CONCLUSION: Anti-PD-1 immunotherapy is effective in the treatment of cancers. These agents can precipitate autoimmune disorders. As the use of anti-PD-1 agents is expected to rise, physicians should be educated about the potential side effects.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus Tipo 1/induzido quimicamente , Nivolumabe/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
6.
J Oncol Pharm Pract ; 26(1): 244-251, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31068087

RESUMO

BACKGROUND: Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1. Nowadays, immune checkpoint inhibitors such as nivolumab are used in the treatment of many different types of cancer. Treatment responses of these agents may be different from standard chemotherapy, and hyperprogression is a new entity that occurs with immune checkpoint inhibitors. We present a case of hyperprogressive disease precipitated by anti-programmed cell death-1 immunotherapy. CASE REPORT: A 25-year-old woman was treated with ipilimumab, dabrafenib plus trametinib, and nivolumab, respectively, for stage IV melanoma. Palliative whole brain radiotherapy was completed due to brain metastases before the administration of nivolumab. After the fourth cycle of nivolumab, the patient's general condition deteriorated and control positron emission tomography/computed tomography confirmed hyperprogression. Also, brain magnetic resonance imaging indicated the hyperprogression of the metastatic lesions. MANAGEMENT AND OUTCOME: After brain magnetic resonance imaging and positron emission tomography/computed tomography showed the hyperprogressive disease, nivolumab was discontinued. Cisplatin and dacarbazine were initiated for melanoma. DISCUSSION: Anti-programmed cell death-1 immunotherapy is effective in cancers. These agents can precipitate hyperprogressive disease. As the use of anti-programmed cell death-1 agents is expected to rise, physicians should be educated about the potential possibility of hyperprogression during the immunotherapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Feminino , Humanos , Imagem por Ressonância Magnética , Melanoma/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
7.
J Oncol Pharm Pract ; 26(1): 252-255, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31382863

RESUMO

Immune checkpoint inhibitors have become a target for pharmacological research in lung cancer. Immune-related adverse events (irAEs) such as pneumonitis, colitis, hepatitis and endocrinopathies have been well characterized in immune checkpoint inhibitors, but coronary toxicities, like acute coronary syndrome, are poorly described. Herein, we report a possible acute coronary syndrome as immune-related adverse event in a lung cancer patient.


Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Idoso , Humanos , Masculino , Recidiva
8.
J Oncol Pharm Pract ; 26(1): 256-258, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31566114

RESUMO

INTRODUCTION: The immune checkpoint inhibitors recently entered to small cell lung cancer (SCLC) stage, firstly in the third and recently in the first lines of therapy. This efficacy comes at the expense of many toxicities including skin toxicity. This toxicity is usually in the form of rash and pruritis; however, rare reactions like psoriasis can also be seen. CASE REPORT: Herein, we report an SCLC case who developed de novo psoriasis while treated with nivolumab as the third-line treatment for SCLC. MANAGEMENT AND OUTCOME: The psoriatic plaques were regressed with the topical highly potent steroid therapy, and immunotherapy was continued without further complications. DISCUSSION: We think that rare adverse events like de novo psoriasis are important considering the expanding role of these agents; their timely recognition and treatment are important in the management of cancer patients.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Psoríase/induzido quimicamente , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores
9.
Int J Cancer ; 146(2): 542-552, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31584197

RESUMO

Our previous researches have identified immunoevasive subtype muscle-invasive bladder cancer (MIBC) characterized with immune cells infiltration patterns. Our study explored the clinical significance, immunoregulatory role and therapeutic value of intratumoral IL22-producing cells in MIBC. Two hundred and fifty-nine formalin-fixed paraffin-embedded MIBC samples and 83 freshly resected MIBC tissues and 391 TCGA MIBC samples were retrospectively evaluated. Immunohistochemistry and flow cytometry were applied to identify immune cell infiltration and functional status. In vitro intervention studies were to test the therapeutic and predictive potential of IL22+ cells. Our data revealed patients with high IL22+ cells infiltration suffered poor overall survival and recurrence-free survival in both training and validation cohorts. Only pT2 patients of combined cohort with low IL22+ cells infiltration gained survival benefits from adjuvant chemotherapy (ACT) significantly. Besides, immune contexture featured with increased pro-tumor cells and immunosuppressive cytokines was identified in patients with high IL22+ cells density. The expression pattern of exhausted and effector markers in CD8+ T cells from high IL22+ cells subgroup indicated their dysfunctional status. Importantly, nivolumab showed tumor-killing efficacy in tumors with high IL22+ cells infiltration, and immunosuppressive contexture with CD8+ T cells exhaustion was abrogated in tumors treated with anti-IL22 antibody. In summary, IL22+ cells infiltration determined immunosuppressive contexture with CD8+ T cell dysfunction. Tumor-infiltrating IL22+ cells could be used as an independent marker to predict prognosis and ACT responses. IL22+ cells infiltration possessed the potential to be a favorable predictor for nivolumab application and IL22 blockade could be a novel therapeutic strategy in MIBC.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Interleucinas/metabolismo , Nivolumabe/farmacologia , Evasão Tumoral/efeitos dos fármacos , Neoplasias da Bexiga Urinária/terapia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Quimioterapia Adjuvante/métodos , Cistectomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Interleucinas/imunologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos , Evasão Tumoral/imunologia , Bexiga Urinária/citologia , Bexiga Urinária/imunologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
10.
Expert Opin Ther Pat ; 30(2): 83-86, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874056

RESUMO

Introduction: TIGIT is an inhibitory receptor expressed by lymphocytes that suppresses the immune response against tumor cells. There is a great need to discover and develop new therapies focused on inhibiting the action of TIGIT and consequently improving the immune response in the various types of cancer. Authors of WO2018102536 patent propose a method to eradicate cancer utilizes anti-TIGIT antibody, etigilimab, in combination with anti-PD-1/PD-L1 antibody, nivolumab.Areas covered: WO2018102536 patent describes a method of cancer combinatorial treatment consisting of the utilization of either a pharmaceutical cocktail containing anti-TIGIT and an anti-PD-L1 antibody.Expert opinion: The results of the clinical trials only support trials regarding the tolerability of therapy with etigilimab, but does not show data related to the combined use of etigilimab and nivolumab.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Nivolumabe/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Humanos , Neoplasias/imunologia , Patentes como Assunto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores Imunológicos/antagonistas & inibidores
11.
Nat Med ; 25(12): 1916-1927, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792460

RESUMO

Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response.


Assuntos
Antígeno CTLA-4/imunologia , Melanoma/tratamento farmacológico , Melanoma/genética , Receptor de Morte Celular Programada 1/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Apresentação do Antígeno/genética , Apresentação do Antígeno/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Masculino , Melanoma/imunologia , Melanoma/patologia , Mutação/genética , Metástase Neoplásica , Nivolumabe/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Transcriptoma/genética , Transcriptoma/imunologia , Sequenciamento Completo do Exoma
12.
S D Med ; 72(10): 454-458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31816206

RESUMO

Several immunotherapeutic agents function against the T cell immune checkpoint inhibitor pathways thereby reestablishing immune response to elusive malignancies. Namely, the programmed death-1 co-receptor (PD-1) or ligand (PD-L1) and cytotoxic T lymphocyte- associated protein 4 (CTLA-4) are well known checkpoint targets of current FDA approved drugs. Among these drugs nivolumab, an IgG4 anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, are used to treat numerous malignancies but carry a large list of potential side effects termed immune-related adverse effects (irAEs). We describe the presentation, clinical course, and resolution of steroid-resistant immune checkpoint inhibitor-induced colitis secondary to administration of these two drugs in a 66-year-old female patient treated with infliximab.


Assuntos
Anticorpos Monoclonais , Colite , Infliximab/uso terapêutico , Idoso , Anticorpos Monoclonais/uso terapêutico , Colite/induzido quimicamente , Colite/imunologia , Colite/terapia , Feminino , Humanos , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos , Resultado do Tratamento
13.
Anticancer Res ; 39(12): 6673-6684, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810932

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs. MATERIALS AND METHODS: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index. RESULTS: Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity. CONCLUSION: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias Bucais/tratamento farmacológico , Bortezomib/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cetuximab/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Fluoruracila/farmacologia , Hormese , Humanos , Técnicas In Vitro , Queratinócitos/efeitos dos fármacos , Mucosa Bucal/citologia , Nivolumabe/farmacologia , Compostos de Platina/farmacologia , Taxoides/farmacologia
14.
Anticancer Res ; 39(12): 6887-6893, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810958

RESUMO

BACKGROUND/AIM: Little information is available about the association between peripheral T-lymphocyte expression of programmed cell death protein 1 (PD1) and the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer (NSCLC). We analyzed the PD1 and cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in peripheral blood T-lymphocytes of patients with NSCLC receiving immune checkpoint inhibitor therapy. PATIENTS AND METHODS: Patients with NSCLC who were scheduled to receive treatment with immune checkpoint inhibitors were prospectively enrolled in this study between November 2017 and November 2018. Peripheral blood samples were obtained within 1 week before or after the initiation of treatment with an immune checkpoint inhibitor. RESULTS: Flow cytometry was conducted in 19 patients. Patients were treated with nivolumab, pembrolizumab, or atezolizumab. The group with a high percentage of PD1+CD4+ T-lymphocytes relative to the total CD4+ T-lymphocyte count had a longer progression-free survival [median=6.0 (95% confidence intervaI=0.5-not estimated) months] than the group with a low percentage of PD1+CD4+ T-lymphocytes [median=1.1 (95% confidence intervaI=0.4-5.0) months; p=0.034, log-rank test]. However, no significant associations were detected with the percentages of CTLA4+CD4+, PD1+CD8+ or CTLA4+CD8+ T-lymphocytes in the peripheral blood. CONCLUSION: A high percentage of peripheral CD4+PD1+ T-lymphocytes was associated with a longer progression-free survival in patients receiving treatment with an immune checkpoint inhibitor. The systemic immune system may have an influence on the efficacy of immune checkpoint inhibitor therapy in patients with NSCLC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Contagem de Linfócito CD4 , Carcinoma Pulmonar de Células não Pequenas/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(50): e18310, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852114

RESUMO

PURPOSE: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer. METHOD: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account. RESULTS: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency. CONCLUSION: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Doenças do Sistema Endócrino/sangue , Neoplasias Pulmonares/sangue , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/sangue , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Saúde Global , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico
16.
Gan To Kagaku Ryoho ; 46(12): 1879-1882, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-31879407

RESUMO

Nivolumab induces several immune-related adverse events. Isolated adrenocorticotropic hormone(ACTH)deficiency has low frequency. A 73-year-old woman with gastric cancer metastasis of the peritoneum was treated with nivolumab as the third-line chemotherapy. After 5 courses of nivolumab, she developed hypothyroidism. After completing 12 courses, peritoneal metastasis increased. We evaluated the metastasis as progression of disease, so treatment with nivolumab was discontinued. Two weeks after the last dosage of nivolumab, she developed general fatigue and appetite loss. At first, we considered that these symptoms were caused by peritoneal metastasis, but progression was not indicated in the CT. Blood levels of cortisol and ACTH were very low. We suspected secondary adrenocortical insufficiency induced by nivolumab. Endocrinological examinations and the results of brain MRIsuggested isolated ACTH deficiency. This is the first report of isolated ACTH deficiency induced by nivolumab in a patient with gastric cancer metastasis of the peritoneum. The symptoms of adrenocortical insufficiency induced by nivolumab overlap with those of peritoneal metastasis, and thus, it may be difficult to confirm a differential diagnosis. When adrenocortical insufficiency is suspected, we should check the blood levels of cortisol and ACTH.


Assuntos
Doenças do Sistema Endócrino , Nivolumabe/efeitos adversos , Neoplasias Gástricas , Hormônio Adrenocorticotrópico , Idoso , Doenças do Sistema Endócrino/induzido quimicamente , Feminino , Humanos , Peritônio , Neoplasias Gástricas/tratamento farmacológico
17.
Hinyokika Kiyo ; 65(9): 363-367, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31697878

RESUMO

A 68-year-old man was referred to our hospital with a right-sided renal tumor identified by ultrasonography at the time of his medical check-up. Computed tomography revealed a well-circumscribed but distorted mass measuring 64×45×57 mm in the right kidney with para-aortic lymph node swelling. Laparoscopic right nephrectomy with para-aortic lymphadenectomy was performed. Histopathological diagnosis was mucinous tubular and spindle cell carcinoma (MTSCC) (pT3a) without lymph node metastasis (pN0). Postoperatively, metastases were identified in the lungs, and the vertebral and iliac bones. The patient was treated with axitinib. The lung nodule progressed and left sacrum metastases appeared even after treatment with axitinib. Therefore, nivolumab was administered as second-line treatment. The metastases in the lungs, as well as vertebral and iliac bone showed complete response to this therapy. MTSCC of the kidney is a rare low-grade renal cell carcinoma without any established systemic therapy for metastatic or unresectable lesions. We report a case of metastatic MTSCC in a patient who showed a favorable response to nivolumab treatment. This is the first report to describe successful treatment of metastatic MTSCC with anti-programmed cell death 1 antibody.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Renais , Nivolumabe/uso terapêutico , Adenocarcinoma Mucinoso/terapia , Idoso , Humanos , Neoplasias Renais/terapia , Masculino , Nefrectomia
18.
Hinyokika Kiyo ; 65(10): 413-419, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31697887

RESUMO

Peritoneal dissemination or metastasis is a relatively rare presentation of renal cell carcinoma. We report four cases of advanced renal cell carcinoma with peritoneal metastases treated with nivolumab. Three cases showed an objective response in the metastatic lesions including peritoneal sites. After nivolumab administration, the computed tomography scan showed a transient enlargement of peritoneal lesions in two cases, which could be considered as pseudoprogression. Temporal changes of neutrophil-tolymphocyte ratio, C-reactive protein, and eosinophil ratio during the clinical course reflected the treatment effect of nivolumab in these patients, indicating that these could be potential biomarkers of the response. To our knowledge, this is the first case series showing therapeutic activity of nivolumab against peritoneal metastases in patients with renal cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Peritoneais , Humanos , Nivolumabe , Tomografia Computadorizada por Raios X
19.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704852

RESUMO

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Tuberculose Latente/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo
20.
Anticancer Res ; 39(11): 6265-6271, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704856

RESUMO

BACKGROUND/AIM: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. RESULTS: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. CONCLUSION: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.


Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Japão , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
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