Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Oncologist ; 25(12): e2013-e2016, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918789

RESUMO

INTRODUCTION: Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine. MATERIALS AND METHODS: A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed. RESULTS: A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%). CONCLUSION: Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.


Assuntos
Fibromatose Agressiva , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica , Fibromatose Agressiva/tratamento farmacológico , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina/efeitos adversos , Vinorelbina
2.
Support Care Cancer ; 28(2): 561-570, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31089820

RESUMO

PURPOSE: The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achieving high-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aim of this study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-related adverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK. METHODS: We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durable response to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression. HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEs and survival. HRQoL data was compared with two norm-based datasets. RESULTS: Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity of any grade occurred in 92% of patients and 43% had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients required steroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyond steroids. Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical role functioning and general health compared with the normative population. There was a trend towards inferior scores in patients with previous exposure to ipilimumab compared with those never exposed to ipilimumab. CONCLUSIONS: Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicity and experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population's unique survivorship needs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Melanoma/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes
4.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233964

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. METHODS: We conducted a multicenter (six cancer centers), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with Common Terminology Criteria for Adverse Events (CTCAE) grade 0 for diarrhea at 12 weeks after IFX initiation. We also assessed cancer outcomes at 1 year using RECIST V1.1 criteria. RESULTS: 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhea CTCAE grade >2 and 115 (90.6%) required hospitalization for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistic regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04 to 0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13 to 8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared with patients with IFX-responsive enterocolitis (37.5%; p=0.013). CONCLUSION: This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Using predefined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI therapy.


Assuntos
Enterocolite/induzido quimicamente , Fármacos Gastrointestinais/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Infliximab/uso terapêutico , Estudos de Coortes , Feminino , Fármacos Gastrointestinais/farmacologia , Humanos , Infliximab/farmacologia , Masculino , Pessoa de Meia-Idade
5.
ESMO Open ; 5(4)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641348

RESUMO

BACKGROUND: Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined. METHODS: All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables. RESULTS: 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 patients treated (ipilimumab=77 episodes, anti-PD1=17 (nivolumab or pembrolizumab), ipilimumab and nivolumab=23 (ipi+nivo)) (seven patients had ir-D/C more than once on different lines of treatment) and >/=grade 3 ir-D/C occurred most frequently (63/519 patients (12%) vs 29/519 (5%) grade 1, and 25/519 (5%) grade 2). Median onset (days) of all-grade ir-D/C after starting ICI therapy was 41 for ipilimumab (IQR 24 to 59, n=77), 91 for anti-PD1 (IQR 46 to 355, n=17) and 45 for ipi+nivo (IQR 24 to 67, n=23). In 71/117 (61%) patients, ir-D/C episodes were treated with CS (17% grade 2; 79% grade 3/4): 54 being steroid-responsive; 17 being steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment. Median grade 3 ir-D/C CS duration was similar across treatments, averaging 58 days. Median overall CS duration (days) was longer in the grade 3/4 D/C steroid-refractory group (94 vs 45 days). Infection developed in 11/71 (15%) CS recipients and in 6/17 (35%) anti-TNF recipients. In 65/117 (55%) patients, ir-D/C episodes were investigated with flexible sigmoidoscopy. Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes, 13/17 (76%), than the steroid-responsive group, 22/41 (54%). CONCLUSION: Rates of grade 3 ir-D/C were higher than reported in clinical trials. The 58-day median duration of CS therapy for grade 3 ir-D/C places a significant number of patients at risk of complications. We demonstrate that microscopic colitis is an important subgroup, advocating biopsies in ir-D/C even with macroscopically normal bowel.


Assuntos
Colite , Melanoma , Neoplasias Cutâneas , Corticosteroides/uso terapêutico , Colite/induzido quimicamente , Diarreia/induzido quimicamente , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Cutâneas/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral
6.
Clin Sarcoma Res ; 10: 1, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31911828

RESUMO

BACKGROUND: Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. METHODS: Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. RESULTS: Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8-14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2-28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3-4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. CONCLUSION: Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

7.
Med Oncol ; 35(10): 131, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30128716

RESUMO

The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3-3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Cuidados Paliativos/métodos , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/tratamento farmacológico , Adulto , Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma Sinovial/mortalidade , Resultado do Tratamento , Adulto Jovem , Gencitabina
8.
Eur J Cancer ; 51(18): 2785-91, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26597444

RESUMO

BACKGROUND: Immunotherapies like the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab show durable clinical benefit in patients with advanced melanoma. Reliable prognostic markers and risk scores in the era of immunotherapy are still lacking. PATIENTS AND METHODS: We collected characteristics and outcomes on 134 patients with metastatic melanoma treated with ipilimumab between 2011 and 2014 at a single centre. Cox regression including multivariable fractional polynomials was used to identify independent markers for overall survival (OS). Internal model validation was done using bootstrap procedures. RESULTS: After a median follow-up of 16.1 months the median OS was 7.1 months (95% confidence interval [CI], 6.5-9.8). Nineteen of 134 patients (14.2%) had tumour remissions, 16 partial and 3 complete; 75% had progressive disease. We identified three independent adverse factors for OS: elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.03, 95% CI 1.02-1.04), Eastern Cooperative Oncology Group performance status >0 (HR 1.91, 95% CI 1.10-3.30), and number of organs involved (NOI) (HR 1.51, 95% CI 1.22-1.86). To build an easy-to-apply risk score, we dichotomized LDH (>upper limit of normal) and NOI (>2) to built 3 prognostic groups: favourable (no adverse factors, N = 17), intermediate (1 adverse factor, N = 38), and poor prognosis (≥2 adverse factors, N = 73). Respective 12 and 18-month OS for the risk groups were: 85% and 73% (favourable), 41% and 29% (intermediate), and 12% and 6% (poor) (p < 0.001). CONCLUSION: We propose a simple prognostic score for survival in patients with advanced melanoma treated with ipilimumab using readily available clinical parameters.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Técnicas de Apoio para a Decisão , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/sangue , Progressão da Doença , Feminino , Humanos , Ipilimumab , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Londres , Masculino , Melanoma/sangue , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA