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1.
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
2.
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
3.
Anticancer Res ; 39(11): 6355-6358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704867

RESUMO

BACKGROUND/AIM: Pneumonitis is a serious complication after radiotherapy of breast cancer. This study aimed to identify its prevalence and potential risk factors. PATIENTS AND METHODS: A total of 606 patients irradiated following breast-conserving surgery or mastectomy were retrospectively analyzed. In patients developing pneumonitis, radiation and clinical parameters were investigated to identify potential risk factors. RESULTS: Eleven patients (1.8%) developed a pneumonitis grade ≥2. Mean doses to the ipsilateral lung were >7 Gy in 5 patients (45%). Of the other patients, 5 had a chronic inflammatory disease. Six patients (55%) had another malignancy (4 previous contralateral breast cancers, 1 previous ovarian and thyroid cancer, 1 synchronous carcinoma-in-situ (pTis) at the contralateral breast). Five patients (45%) received chemotherapy including taxanes and 4 patients (36%) received trastuzumab. CONCLUSION: The prevalence of pneumonitis was 1.8%. Potential risk factors included mean radiation dose to ipsilateral lung >7 Gy, systemic treatment with taxanes or trastuzumab, chronic inflammatory disease and history of another malignancy.


Assuntos
Neoplasias da Mama/radioterapia , Pneumonite por Radiação/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma in Situ/radioterapia , Feminino , Humanos , Pulmão/efeitos da radiação , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Prednisolona/uso terapêutico , Prevalência , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
4.
Medicine (Baltimore) ; 98(41): e17348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593084

RESUMO

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Imunitário/induzido quimicamente , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos
5.
Anticancer Res ; 39(10): 5741-5745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570476

RESUMO

BACKGROUND/AIM: Cardiovascular risk factors (CVRFs) predict cardiotoxicity in cancer patients but their role in late cardiac toxicity is less clear. PATIENTS AND METHODS: This was a retrospective analysis of patients treated with anthracyclines (A) and/or trastuzumab (T) and a correlation with early (≤5 years) or late (>5 years) cardiac toxicity, and baseline CVRFs and CVRFs at toxicity time. RESULTS: A total of 610 patients were included, 422 with (Group A) and 188 without (Group B) baseline CVRFs. In group A toxicity incidence was 4.7% with all events during treatment or immediately after [mean onset time 0.7 years (range=0.2-1.6)]. Events rate was 3.2% in group B with all events after five years [mean time onset 6.9 years (range=5.2-7.5)]. All group B patients who developed late cardiac toxicity presented with CVRFs at the time of toxicity not reported before. CONCLUSION: CVRFs could predict late cardiac toxicity and their control should be part of the survivorship program.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiopatias/induzido quimicamente , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
6.
Med Oncol ; 36(11): 94, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605245

RESUMO

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Fígado , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
7.
Lancet ; 394(10200): 793-804, 2019 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-31478503

RESUMO

Antibody-drug conjugates (ADCs) are immunoconjugates comprised of a monoclonal antibody tethered to a cytotoxic drug (known as the payload) via a chemical linker. The ADC is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. To date, five ADCs have received market approval and over 100 are being investigated in various stages of clinical development. In this Therapeutics paper, we review recent clinical experience with the approved ADCs and other promising late-stage candidates on the horizon, following an overview of the biology and chemistry of ADCs and how the individual components of an ADC (antibody [or target], linker and conjugation chemistry, and cytotoxic payload) influence its activity. We briefly discuss opportunities for enhancing ADC efficacy, drug resistance, and future perspectives for this novel antibody-based molecular platform, which has great potential to make a paradigm shift in cancer chemotherapy.


Assuntos
Anticorpos Monoclonais , Antineoplásicos Imunológicos , Imunoconjugados , Neoplasias/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacocinética , Imunoconjugados/farmacologia
9.
Acute Med ; 18(3): 197-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536059

RESUMO

The advent of immunotherapy in oncology has led to the emergence of a new spectrum of adverse effects. A number of these have the potential to contribute to life-threatening outcomes; and therefore require prompt identification and aggressive treatment to optimise management. In this report, we describe a case of pembrolizumab-induced CTCAE (common toxicity criteria for adverse events) grade 4 myositis in a non-small cell lung cancer patient.


Assuntos
Adenocarcinoma de Pulmão , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Miosite , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Miosite/induzido quimicamente
11.
Expert Opin Investig Drugs ; 28(9): 799-809, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398295

RESUMO

Introduction: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Mycosis fungoides and Sézary syndrome are the most common CTCL. Early stage disease follows a protracted course, carries a 5-year disease specific survival of 97% and can be treated with skin-directed therapies. Widespread, advanced disease has a 5-year OS of less than 25% and necessitates systemic treatment. Allogeneic stem cell transplantation is a potentially curative treatment option for advanced CTCL, however, transplant-related morbidity and mortality must be considered and a risk-benefit assessment performed on individual basis. Areas covered: Herein, we provide a review of investigative drugs in early-stage trials for the treatment of cutaneous CTCL, including topically applied immunomodulators such as replicating herpes virus or toll-like receptor 7/8 agonist resiquimod and systemic therapies with monoclonal antibodies, such as anti-CD47, recombinant cytotoxic interleukin 2 fusion protein anti-KIR3DL2 antibody and anti-miR-155 antibody. Expert Opinion: Among the reviewed drugs, resiquimod shows promising clinical efficacy with good tolerability in early CTCL. In refractory or relapsed disease, intratumoral anti-CD47-, anti-CCR4- and anti-KIR3DL2-antibodies show high response rates, however, latter two also show considerable toxicity. Larger trials are needed to better evaluate the discussed therapies.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/efeitos adversos , Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Estadiamento de Neoplasias , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
12.
Medicine (Baltimore) ; 98(29): e16417, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335691

RESUMO

We aimed to assess serial F-FDG PET/CT imaging according to morphological (RECIST1.1, iRECIST) and functional (PERCIST, PECRIT) criteria to predict clinical response to therapy in patients with advanced melanoma receiving immune checkpoint blocking agents.Retrospective data collection and analysis was done for 37 patients with unresectable metastatic cutaneous melanoma eligible for immunotherapy (cycles: 4 for ipilimumab and pembrolizumab/ 6 for nivolumab).F-FDG PET/CT imaging was performed prior to (F-FDG PET/CT 0) and 14 weeks after ICI onset (F-FDG PET/CT 1). Some cases during the follow-up required imaging (F-FDG PET/CT 2). Assessment of patient response to treatment was done according to RECIST1.1, iRECIST, PERCIST and PECRIT criteria.Among 37 assessed patients, 27 had 1 line of ICI, 8 had 2 lines of ICI and 2 patients had 3 lines of ICI: total of 49 PET/CTs. Mean time between initiation of ICI and F-FDG PET/CT (1 or 2) were respectively 13.82 ±â€Š4.32 and 24.73 ±â€Š9.53 weeks. Time between F-FDG PET/CT 1 and F-FDG PET/CT 2 was at mean +/- SD: 11.19w ±â€Š5.59. Median PFS was 29.62 months (range 22.52-36.71) (P = .001: RECIST 1.1), (P < .0001: iRECIST), (P = .000: PERCIST), (P = .072: PECRIT). Median OS was 36.62 months (30.46-42.78) (P = .005: RECIST 1.1), (P < .0001: iRECIST), (P = .001: PERCIST), (P = .082 PECRIT).F-FDG PET/CT could detect eventual ICI-response in patients with metastatic melanoma undergoing ICI using iRECIST and PERCIST criteria.


Assuntos
Anticorpos Monoclonais Humanizados , Ipilimumab , Melanoma , Nivolumabe , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias Cutâneas , Tomografia Computadorizada por Raios X/métodos , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos Antineoplásicos , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Masculino , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Melanoma/patologia , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
13.
Medicine (Baltimore) ; 98(30): e16439, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348245

RESUMO

BACKGROUND: We performed the meta-analysis to evaluate the overall safety of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor treatment for lung cancer patients. METHOD: Randomized controlled trials were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk ratio (RR) of PD-1/PD-L1 inhibitor treatment-related death, treatment-related adverse events, any serious events, and any events leading to discontinuation were all taken into account for the final evaluation. RESULTS: Fourteen studies were collected for the meta-analysis. The RR of treatment-related death for PD-1/PD-L1 was significantly lower than that of the control group (RR = 0.37, 95% confidence interval, CI: [0.21, 0.66]). Similar analysis results could also be seen for the RR of treatment-related adverse events and adverse events leading to discontinuation. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation (RR = 1.68, 95% CI: [1.22, 3.32]). The RR of overall treatment-related adverse events was lower in nivolumab (PD-1) than that of the control group (nivolumab + ipilimumab) (RR = 0.77, 95% CI: [0.65, 0.90]). Similar analysis results could also be seen in the RR of treatment-related adverse events for grade 3 to 5 and adverse events leading to discontinuation. CONCLUSION: Compared with chemotherapy, RR of the treatment-related deaths associated with PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while it did not increase the RR when they were combined with chemotherapy or other drugs. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/mortalidade , Gradação de Tumores , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
14.
Medicine (Baltimore) ; 98(27): e16324, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277179

RESUMO

BACKGROUND: Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) drugs treatment-related adverse events (AEs) are not uniform based on current study for patients with cancer. The study aimed to provide a complete toxicity profile and toxicity spectrum for anti-PD-1 and anti-PD-L1 drugs. METHODS: All systematic reviews (SRs) with meta-analyses (MAs) relate to the anti-PD-1 and anti-PD-L1 drugs and SRs will be searched in the database of PubMed, Embase, Cochrane Library, and Web of Science from inception to February 2019. Eligible publications must have reported site, organ, or system level data on treatment-related AEs. The following will extract from each SRs: first author, year of publication, country of origin, number of origin study, number of patients enrolled, participant characteristics, duration of cancer diagnosis, cancer types, detailed description of treatment, and occurrence of AEs. Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) and A Measurements Tool to Assess Systematic Reviews 2 (AMSTAR-2) will be used to assess the reporting and methodological quality of SRs/MAs. The characteristics of the included SRs/MAs and their quality will descriptively summarized using systematically structured tables. A network meta-analysis (NMAs) approach versus a narrative synthesis will be used to examine data synthesis considered. Odds ratios and 95% credibility intervals will be used as summary statistics. Evidence mapping (EM) method will to present the evidence landscape related to anti-PD-1 and anti-PD-L1 drugs treatment-related AEs for patients with cancer. DISCUSSION: The results of the overview will be submitted to a peer-reviewed journal for publication. ETHICS AND DISSEMINATION: Because this study is not a clinical study, and we will search and evaluate only existing sources of literature. So, ethical approval is not required.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/imunologia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , Humanos , Metanálise como Assunto , Revisão Sistemática como Assunto
15.
Expert Rev Clin Pharmacol ; 12(8): 815-824, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31287333

RESUMO

Objective: Breast cancer remains to be the globally leading female cancer. About 15% to 20% of breast cancers have human epidermal growth factor receptor 2 (HER2)-positive tumors - a more aggressive breast cancer subtype with shortened survival. In the light of new and updated trial data on trastuzumab therapy for HER2-positive early-stage breast cancer (EBC), we conducted a systematic review and meta-analysis to update the pooling of its relative treatment effects. Methods: Systematic search was performed through Pubmed and Scopus to identify studies comparing survival outcomes and risks of heart toxicity effects of adjuvant trastuzumab with chemotherapy versus chemotherapy alone for HER2-positive EBC patients. Results: Based on the eight included studies in the review, combining trastuzumab with chemotherapy continues to show lowered death and relapse risks by one-third. The decision to initiate trastuzumab, however, needs to be prudently deliberated as two to three times more cardiotoxicity risk was shown to be associated with its use. Conclusion: Administering adjuvant trastuzumab in a weekly cycle concurrently with anthracycline-taxane chemotherapy regimen appears to be a preferable option to optimize its favorable effect in improving DFS and to prevent significantly higher risk for cardiotoxic effects.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversos
16.
Acta Gastroenterol Belg ; 82(2): 322-325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314196

RESUMO

Colorectal cancer is one of the most frequently diagnosed malignancies worldwide. One of the most important developments in the management of metastatic colorectal cancer is targeted therapy. Bevacizumab, a monoclonal antibody inhibiting VEGF induced angiogenesis, has been accepted as safe and efficient in the treatment of metastatic colorectal cancer for more than a decade. Addition of bevacizumab to fluorouracil-based chemotherapy is also associated with severe adverse events. We present a case of bevacizumab-induced bowel ischaemia associated with gastrointestinal haemorrhage.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Metástase Neoplásica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Hemorragia Gastrointestinal , Humanos
17.
Lancet Haematol ; 6(8): e429-e437, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296423

RESUMO

BACKGROUND: Lenalidomide plus rituximab is approved to treat patients with relapsed or refractory follicular lymphoma. Obinutuzumab has been shown to enhance antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine the activity and safety of lenalidomide plus obinutuzumab in previously treated patients with relapsed or refractory follicular lymphoma. METHODS: In this multicentre, single-arm, phase 2 study, patients were enrolled from 24 Lymphoma Academic Research Organisation centres in France. Eligible patients (age ≥18 years) had histologically confirmed CD20-positive relapsed or refractory follicular lymphoma of WHO grade 1, 2, or 3a; an ECOG performance status of 0-2; and received at least one previous rituximab-containing therapy. Patients received oral lenalidomide (20 mg) plus intravenously infused obinutuzumab as induction therapy (1000 mg; six 28-day cycles), 1-year maintenance with lenalidomide (10 mg; 12 28-day cycles; days 2-22) plus obinutuzumab (1000 mg; alternate cycles), and 1-year maintenance with obinutuzumab (1000 mg; six 56-day cycles; day 1). The primary endpoint was the proportion of patients who achieved an overall response at induction end as per investigator assessment using the 1999 international working group criteria. The secondary endpoints were event-free survival, progression-free survival, overall survival, and safety. Analyses were per-protocol; the efficacy population included all patients who received at least one dose of both obinutuzumab and lenalidomide, and the safety population included all patients who received one dose of either investigational drug. The study is registered with ClinicalTrials.gov, number NCT01582776, and is ongoing but closed to accrual. FINDINGS: Between June 11, 2014, and Dec 18, 2015, 89 patients were recruited and 86 patients were evaluable for efficacy and 88 for safety. Median follow-up was 2·6 years (IQR 2·2-2·8). 68 (79%) of 86 evaluable patients (95% CI 69-87) achieved an overall response at induction end, meeting the prespecified primary endpoint. At 2 years, event-free survival was 62% (95% CI 51-72), progression-free survival 65% (95% CI 54-74), duration of response 70% (95% CI 57-79), and overall survival 87% (95% CI 78-93). Complete response was achieved by 33 (38%, 95% CI 28-50) of 86 patients at induction end, and the proportion of patients achieving a best overall response was 70 (81%, 95% CI 72-89) and 72 (84%, 74-91) of 86 patients during induction and treatment, respectively. The most common adverse events were asthenia (n=54, 61%), neutropenia (n=38, 43%), bronchitis (n=36, 41%), diarrhoea (n=35, 40%), and muscle spasms (n=34, 39%). Neutropenia was the most common toxicity of grade 3 or more; four (5%) patients had febrile neutropenia. 57 serious adverse events were reported in 30 (34%) of 88 patients. The most common serious adverse events were basal cell carcinoma (n=5, 6%), febrile neutropenia (n=4, 5%), and infusion-related reaction (n=3, 3%). One patient died due to treatment-related febrile neutropenia. INTERPRETATION: Our data shows that lenalidomide plus obinutuzumab is active in previously treated patients with relapsed or refractory follicular lymphoma, including those with early relapse, and has a manageable safety profile. Randomised trials of new immunomodulatory regimens, such as GALEN or using GALEN as a backbone, versus lenalidomide plus rituximab, are warranted. FUNDING: Lymphoma Academic Research Organisation, and Celgene and Roche.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígenos CD20/metabolismo , Antineoplásicos Imunológicos/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Lenalidomida/efeitos adversos , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Recidiva , Taxa de Sobrevida , Resultado do Tratamento
18.
Hinyokika Kiyo ; 65(5): 157-161, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31247693

RESUMO

A 43-year-old man underwent nephrectomy for right renal cell carcinoma (cT3aN0M1 (PUL), clear cell carcinoma). Thereafter, he was treated with sunitinib for lung metastases as the first-line therapy for three months. Because lung metastases progressed and new bone metastases appeared, nivolumab was started for the second-line treatment. Although the cancer progression was suppressed by multidisciplinary treatment combined with systemic immunotherapy and local radiation therapy, he developed severe acute kidney injury with cortical swelling after eighteen months of nivolumab treatment. A diagnosis of acute interstitial nephritis induced by nivolumab was made based on biopsy findings. Treatment with prednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function. We must consider the possibility of immunerelated adverse events, especially nivolumab-induced acute kidney injury, even after long-term treatment.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Nefrite Intersticial , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Nefrite Intersticial/induzido quimicamente , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico
19.
Autoimmun Rev ; 18(8): 805-813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176871

RESUMO

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças Reumáticas/induzido quimicamente , Humanos , Neoplasias/imunologia
20.
Crit Rev Oncol Hematol ; 141: 23-35, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202955

RESUMO

Recently, tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICPIs) have emerged as new classes of anticancer therapies. Although generally considered less toxic than cytotoxic chemotherapy, these new drugs can cause significant unanticipated side effects including thyroid dysfunction. This review provides a literature assessment of thyroid dysfunctions induced by TKI and ICPIs. We intend to define for these two classes the frequency of thyroid involvement, the potential mechanisms that result in this toxicity, the clinical-biological impact and the therapeutic management. Detection of thyroid dysfunction requires monitoring of TSH, in combination with free T4 if needed and, depending on the clinical impact and the kinetics of biological abnormalities, starting symptomatic treatment of hyperthyroidism and/or correcting hypothyroidism.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Doenças da Glândula Tireoide/induzido quimicamente , Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Hipotireoidismo/patologia , Hipotireoidismo/terapia , Neoplasias/fisiopatologia , Inibidores de Proteínas Quinases/uso terapêutico , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/patologia , Doenças da Glândula Tireoide/terapia , Testes de Função Tireóidea
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