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1.
Recent Results Cancer Res ; 214: 1-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473848

RESUMO

Exploiting the unique specificity of monoclonal antibodies has revolutionized the treatment and diagnosis of haematological and solid organ malignancies; bringing benefit to millions of patients over the past decades. Recent achievements include conjugating antibodies with toxic payloads resulting in superior efficacy and/or reduced toxicity, development of molecular imaging techniques targeting specific antigens for use as predictive and prognostic biomarkers, the development of novel bi- and tri-specific antibodies to enhance therapeutic benefit and abrogate resistance and the success of immunotherapy agents. In this chapter, we review an overview of antibody structure and function relevant to cancer therapy and provide an overview of pivotal clinical trials which have led to regulatory approval of monoclonal antibodies in cancer treatment. We further discuss resistance mechanisms and the unique side effects of each class of antibody and provide an overview of emerging therapeutic agents.


Assuntos
Anticorpos Monoclonais/farmacologia , Imunoterapia , Neoplasias/terapia , Ensaios Clínicos como Assunto , Humanos
2.
J Clin Neurosci ; 68: 45-50, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371189

RESUMO

There is limited information on the patterns of care and outcomes of high grade gliomas (HGGs) in young adults, in particular, the impact it has on a person's employment. We retrospectively identified young adult patients (age ≤ 40 years old) with newly diagnosed high grade gliomas treated between January 2013 and June 2018 across four major neuro-oncology centres in Australia. Patient demographics, tumour characteristics and treatment parameters were collected and outcomes determined. A total of 113 patients were identified with a median follow up of 27.0 months (range 1.0-70.2 months). The median age was 31 years, majority were male (65%) and employed (71.6%). IDH mutations were detected in 66 (62%) cases. The median progression-free survival (PFS) was 38.0 months (95% CI 23.3-52.7 months) and median overall survival (OS) was not reached. Patients with IDH wild type anaplastic astrocytoma and glioblastoma had a significantly shorter median PFS (19.3 months vs. NR, p = 0.001) and median OS (43.5 months vs NR, p = 0.007) than those with IDH mutated grade III anaplastic astrocytoma and oligodendroglioma. There was no significant difference in median OS or PFS between patients who underwent gross or subtotal tumour resection. Significantly, after diagnosis only 36 (32%) patients reported being employed. Young patients with IDH wild type astrocytomas and glioblastoma had better outcomes than reported historical controls. Most patients did not continue in employment post diagnosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30426665

RESUMO

BACKGROUND: There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab. METHOD: We retrospectively identified patients (pts) with metastatic melanoma treated with three-weekly nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg) for four cycles followed by nivolumab monotherapy (3 mg/kg) fortnightly. Patient demographics and treatment parameters were collected and outcomes determined. RESULTS: A total of 45 pts received combination treatment with a median follow up of 8.7 months (range 0.33-25.9 months). A total of 67% were male, and BRAF V600 mutations detected in 38%. At treatment commencement, 14 (31%) pts had brain metastases, 51% had an elevated LDH and 18 (40%) were treatment-naive. Almost a third (30%) required corticosteroids for symptom control or management of prior toxicities. Nineteen (42%) patients had prior anti-PD-1 therapy. The disease control rate (DCR) was 54% and objective response rate (ORR) was 29%. Of pts treated with prior immune checkpoint inhibitors, the DCR and ORR were 50% and 33%, respectively. Intracranial responses were observed in 18% (n = 2). The median progression-free survival (PFS) was 5.8 months (95% Confidence interval (CI), 2.9-14.1 months). PFS was higher in treatment naïve patients compared to those who had prior immunotherapy (6.2 months vs 4.9 months, P = 0.59). The median OS was 17.4 months (95% CI, 7.1-NR). pts requiring corticosteroids had a shorter PFS (4.9 months vs 6.8 months) and OS (7.1 months vs NR, P = 0.01).Treatment-related adverse events of any grade were experienced by 88% of pts, with 54% having grade 3-4 adverse events. Treatment discontinuation due to adverse events occurred in 44% of pts. CONCLUSION: In this study, responses to combination immunotherapy were lower than reported. Patients treated with prior immunotherapy had similar responses as treatment-naïve pts. The toxicity profile seen in this study is similar to those reported in clinical trials.

5.
Theranostics ; 8(15): 4199-4209, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30128047

RESUMO

B7-H3 is a transmembrane protein widely expressed in a variety of cancers and has been shown to play a role in anti-tumor immunity. This study aims to develop a molecular imaging probe to identify B7-H3 expression in tumors and to develop 89Zr-DS-5573a as a theranostic that could aid patient selection in clinical Phase I studies. Methods: The anti-B7-H3 humanised monoclonal antibody DS-5573a was labeled with zirconium-89 (89Zr-), and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution and imaging studies were performed with positron emission tomography and magnetic resonance imaging (PET/MRI) studies to identify and quantitate 89Zr-DS-5573a tumor uptake in a B7-H3-positive breast cancer model (MDA-MB-231) and a B7-H3-negative murine colon cancer model (CT26). Imaging and biodistribution studies were also performed in MDA-MB-231 tumor-bearing SCID mice in the absence and presence of therapeutic DS-5573a antibody dose (3 mg/kg DS-5573a). Results:89Zr-DS-5573a showed high and specific binding to B7-H3-expressing MDA-MB-231 cells (immunoreactivity on day 0, 75.0 ± 2.9%), and low binding to B7-H3-negative CT26 cells (immunoreactivity on day 0, 10.85 ± 0.11%) in vitro. 89Zr-DS-5573a demonstrated good serum stability in vitro with 57.2 ± 2.0% of immunoreactivity remaining on day 7. In vivo biodistribution studies showed high uptake of 89Zr-DS-5573a in B7-H3-expressing MDA-MB-231 tumor-bearing mice, achieving 32.32 ± 6.55 %ID/g on day 7 post injection in BALB/c nu/nu mice and 25.76 ± 1.79 %ID/g in SCID mice, with minimal evidence of non-specific uptake in normal tissues, and excellent tumor localization on PET/MRI. In a combined imaging/therapy study, receptor saturation was demonstrated in tumors responding to therapy. Conclusion:89Zr-DS-5573a demonstrates specific and prolonged targeting of B7-H3-expressing tumors in vivo. Saturation of binding sites was demonstrated in tumors responding to DS-5573a therapy. These results indicate that 89Zr-DS-5573a has potential to target B7-H3-expressing tumors in cancer patients. Furthermore 89Zr-DS-5573a has the potential to provide important insights into T cell biology through its specific binding to B7-H3.

6.
Oncologist ; 23(7): 849-851, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29666298

RESUMO

Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved. This study describes for the first time a case of delayed autoimmunity occurring 8 months after discontinuing treatment with the anti-PD-1 antibody nivolumab in a patient with metastatic melanoma. The case highlights the need for ongoing surveillance of patients treated with immune checkpoint inhibitors even after cessation of therapy, especially as patients increasingly stop treatment after achieving durable responses.

7.
Front Immunol ; 9: 411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29552014

RESUMO

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis, was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection. We evaluated these two immune stimulants in combination with melanoma with the aim of developing a more effective immunotherapy and to assess toxicity. In this phase I study, patients with histologically confirmed stage III/IV metastatic melanoma received IL BCG injection followed by up to four cycles of intravenous ipilimumab (anti-CTLA-4) (ClinicalTrials.gov number NCT01838200). The trial was discontinued following treatment of the first five patients as the two patients receiving the escalation dose of BCG developed high-grade immune-related adverse events (irAEs) typical of ipilimumab monotherapy. These irAEs were characterized in both patients by profound increases in the repertoire of autoantibodies directed against both self- and cancer antigens. Interestingly, the induced autoantibodies were detected at time points that preceded the development of symptomatic toxicity. There was no overlap in the antigen specificity between patients and no evidence of clinical responses. Efforts to increase response rates through the use of novel immunotherapeutic combinations may be associated with higher rates of irAEs, thus the imperative to identify biomarkers of toxicity remains strong. While the small patient numbers in this trial do not allow for any conclusive evidence of predictive biomarkers, the observed changes warrant further examination of autoantibody repertoires in larger patient cohorts at risk of developing irAEs during their course of treatment. In summary, dose escalation of IL BCG followed by ipilimumab therapy was not well tolerated in advanced melanoma patients and showed no evidence of clinical benefit. Measuring autoantibody responses may provide early means for identifying patients at risk from developing severe irAEs during cancer immunotherapy.

8.
AAPS J ; 20(2): 43, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29520671

RESUMO

The selection of therapeutic dose for the most effective treatment of tumours is an intricate interplay of factors. Molecular imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT) can address questions central to this selection: Does the drug reach its target? Does the drug engage with the target of interest? Is the drug dose sufficient to elicit the desired pharmacological effect? Does the dose saturate available target sites? Combining functional PET and SPECT imaging with anatomical imaging technologies such as magnetic resonance imaging (MRI) or computed tomography (CT) allows drug occupancy at the target to be related directly to anatomical or physiological changes in a tissue resulting from therapy. In vivo competition studies, using a tracer amount of radioligand that binds to the tumour receptor with high specificity, enable direct assessment of the relationship between drug plasma concentration and target occupancy. Including imaging studies in early drug development can aid with dose selection and suggest improvements for patient stratification to obtain higher effective utility from a drug after approval. In this review, the potential value of including translational receptor occupancy studies and molecular imaging strategies early on in drug development is addressed.

9.
J Cancer Educ ; 33(3): 500-504, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27581433

RESUMO

With the increasing incidence of cancer and related survival, junior doctors are more commonly involved the management of oncology patients. A comprehensive oncology curriculum has been developed and adopted across medi-cal schools in Australia. However, it was not designed to inform how medical students should be taught, and whether curriculum content translates to knowledge and competency can depend on its implementation. We have conducted a literature review of PubMed, Embase and Cochrane databases to identify and summarise the evidence for novel approaches to delivering the undergraduate oncology curriculum. Numerous effective approaches have been developed across areas of prevention, clinical examination through simulation, the multidisciplinary team, psycho-oncology, palliative care and even research. There is growing focus on a holistic and multidisciplinary approach to cancer education although direct clinical exposure and interactions with cancer patients is still crucial. Medical schools may also have an under-recognised role in promoting positive health behaviour if their graduates are to convey these preventative measures to their patients. Application of such methods relies upon clinicians and medical educators to consider the practicability and relevance of specific implementation in their local context.

10.
Cancer Treat Rev ; 59: 1-21, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28715775

RESUMO

The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits. Despite the therapeutic success of existing HER2 therapies, personalising treatment and overcoming resistance to these therapies remains a significant challenge. The heterogeneous intra-tumoural HER2 expression and lack of fully predictive and prognostic biomarkers remain significant barriers to improving the use of HER2 antibodies. Imaging modalities using radiolabelled pertuzumab and trastuzumab allow quantitative assessment of intra-tumoural HER2 expression, HER2 antibody saturation and the success of different drug delivery systems to be assessed. Molecular imaging with HER2 antibodies has the potential to be a non-invasive, predictive and prognostic technique capable of influencing therapeutic decisions, predicting response and failure of treatments as well as providing insights into receptor recycling and signalling. Similarly, conjugating HER2 antibodies with novel toxic payloads or combining HER2 antibodies with cellular immunotherapy provide exciting new opportunities for the management of tumours overexpressing HER2. Future research will lead to higher therapeutic responses, lower toxicities and providing insight into the mechanisms of resistance to HER2-targeted treatments.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia de Alvo Molecular/métodos , Receptor ErbB-2/genética , Adulto , Idoso , Neoplasias da Mama/mortalidade , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Receptor ErbB-2/efeitos dos fármacos , Análise de Sobrevida , Trastuzumab/administração & dosagem , Resultado do Tratamento
11.
Crit Care Resusc ; 19(2): 159-166, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28651512

RESUMO

OBJECTIVE: Metastatic solid organ cancer is associated with a poor prognosis, and admission of patients with these cancers to the intensive care unit remains a dilemma. We aimed to assess outcomesin a cohort of these patients who were admitted to the ICU of a general tertiary centre. DESIGN, SETTING AND PATIENTS: A retrospective observational study of patients with incurable metastatic solid organ malignancies who had unplanned admission to a tertiary hospital ICU between 1 January 2010 and 30 June 2015. MAIN OUTCOME MEASURES: Survival outcomes up to 1 year after ICU admission, and functional outcomes as measured by Eastern Cooperative Oncology Group (ECOG) grade up to 3 months after ICU discharge. We also determined rates of advance care planning documentation. RESULTS: A total of 101 patients were treated in the ICU during the study period. Hospital, 30-day and 1-year mortality rates were 35%, 41% and 77%, respectively, and the median survival was 2.3 months (95% CI, 1.1-3.9 months). On multivariable analysis, lowest albumin level (hazard ratio [HR], 1.10; 95% CI, 1.04-1.15) and highest white cell count (HR, 1.03; 95% CI, 1.00-1.07) were significant, although they were marginal predictors of poorer overall survival. Higher ECOG grade showed a trend towards significance (HR, 1.60; 95% CI, 0.94-2.73; P = 0.08). In patients alive and assessable at 1 month, 17/31 (55%) had functionally declined. At 3 months, 15/22 surviving patients (68%) had returned to their baseline, pre-ICU admission ECOG grade. Ninety per cent had no advance care directive and twothirds did not have a medical enduring power of attorney. CONCLUSIONS: Survival is poor in patients with metastatic cancer after emergent ICU admission, although functional state is often recovered by 3 months in surviving patients. Albumin level, white cell count and ECOG grade are simple prognostic markers of survival.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva , Metástase Neoplásica/terapia , Centros de Atenção Terciária , Atividades Cotidianas/classificação , Diretivas Antecipadas , Idoso , Austrália , Biomarcadores , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Albumina Sérica/metabolismo , Análise de Sobrevida , Resultado do Tratamento
12.
Br J Cancer ; 116(12): 1558-1563, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28524161

RESUMO

BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS). RESULTS: A total of 66 pts were identified with a median follow up of 7.0 months (range 0.8-24.5 months). A total of 68% were male and 45% BRAF V600 mutation positive. At PD-1 antibody commencement, 50% had an elevated LDH; 64% had local therapy to BM prior to commencing anti-PD1, of which 5% had surgical resection, 14% stereotactic radiosurgery (SRS), 18% whole-brain radiotherapy (WBRT), 27% had surgery and radiotherapy. Twenty-one per cent started anti-PD-1 as first line systemic therapy. No pt had prior anti-PD-1 treatment. The IC overall RR was 21 and DCR 56%. Responses occurred in 21% of pts with symptomatic BM. The median OS was 9.9 months (95% CI 6.93-17.74). Pts with symptomatic BM had shorter PFS than those without symptoms (2.7 vs 7.4 months, P=0.035) and numerically shorter OS (5.7 vs 13.0 months, P=0.068). Pts requiring corticosteroids also had a numerically shorter PFS (3.2 vs 7.4 months, P=0.081) and OS (4.8 vs 13.1 months, P=0.039). CONCLUSIONS: IC responses to anti-PD-1 antibodies occur in pts with BM, including those with symptomatic BM requiring corticosteroids. Prospective trials evaluating anti-PD-1 therapy in pts with BM are underway.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Melanoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Terapia Combinada , Craniotomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Melanoma/complicações , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Radiocirurgia , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Taxa de Sobrevida , Avaliação de Sintomas , Adulto Jovem
14.
Australas J Dermatol ; 58(3): e109-e112, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27170423

RESUMO

Dermatological toxicity is one of the most commonly reported immune-related adverse events in patients receiving checkpoint inhibitor immunotherapy. We report the gradual development of a widespread bullous pemphigoid-like reaction in a metastatic melanoma patient 8 months after commencing treatment with the programmed-death-1 (PD-1) inhibitor pembrolizumab, requiring prolonged corticosteroid therapy. This case highlights the potential for insidious and late development of severe cutaneous toxicity following PD-1 inhibitor therapy and suggests that even prolonged immunosuppression may not necessarily compromise the efficacy of PD-1 inhibition in advanced melanoma.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Erupção por Droga/etiologia , Melanoma/terapia , Penfigoide Bolhoso/induzido quimicamente , Neoplasias Cutâneas/terapia , Adulto , Humanos , Masculino , Melanoma/secundário , Neoplasias Cutâneas/patologia , Fatores de Tempo
16.
J Nucl Med ; 57(6): 974-80, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26940768

RESUMO

UNLABELLED: Subtype A2 of the erythropoietin-producing hepatocellular tyrosine kinase (EphA2) cell surface receptor is expressed in a range of epithelial cancers. This study evaluated the molecular imaging of EphA2 expression in vivo in mouse tumor models using SPECT/MR and PET/MR and a humanized anti-EphA2 antibody, DS-8895a. METHODS: DS-8895a was labeled with (111)In, (125)I, and (89)Zr and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen-binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution, imaging, and pharmacokinetic studies were performed with SPECT/MR and PET/MR. A dose-escalation study was also performed to determine EphA2 receptor saturability through tissue and imaging quantitative analysis. RESULTS: All conjugates demonstrated good serum stability and specific binding to EphA2-expressing cells in vitro. In vivo biodistribution studies showed high uptake of (111)In-CHX-A″-DTPA-DS-8895a and (89)Zr-Df-Bz-NCS-DS-8895a in EphA2-expressing xenograft models, with no specific uptake in normal tissues. In comparison, retention of (125)I-DS-8895a in tumors was lower because of internalization of the radioconjugate and dehalogenation. These results were confirmed by SPECT/MR and PET/MR. EphA2 receptor saturation was observed at the 30 mg/kg dose. CONCLUSION: Molecular imaging of tumor uptake of DS-8895a allows noninvasive measurement of EphA2 expression in tumors in vivo and determination of receptor saturation. (89)Zr-Df-Bz-NCS-DS-8895a is suited for human bioimaging trials on the basis of superior imaging characteristics and will inform DS-8895a dose assessment and patient response evaluation in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/química , Transformação Celular Neoplásica , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos , Receptor EphA2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Zircônio/química , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacocinética , Linhagem Celular Tumoral , Desferroxamina/análogos & derivados , Desferroxamina/química , Feminino , Humanos , Isotiocianatos/química , Camundongos , Ácido Pentético/química , Controle de Qualidade , Receptor EphA2/imunologia , Distribuição Tecidual
17.
Biomedicines ; 4(3)2016 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28536381

RESUMO

Antibody-drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance.

18.
J Clin Neurosci ; 24: 78-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26549675

RESUMO

This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, p<0.0001). All patients progressed after treatment for first progression with 43 patients (45%) receiving treatment at second progression. To our knowledge this is the first population-based pattern of care survey of treatment for rGBM in an era where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Neoplasias Encefálicas/mortalidade , Progressão da Doença , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Período Pós-Operatório , Estudos Retrospectivos
19.
Asian J Surg ; 39(3): 144-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26116405

RESUMO

BACKGROUND: Radioembolization with yttrium microspheres is an established therapeutic modality for primary and secondary hepatic malignancies, with studies demonstrating improved overall survival. There remains a paucity of data on cholecystitis as a complication of radioembolization. We describe a small series of patients who developed cholecystitis as a result of radioembolization. METHODS: Patients who had developed cholecystitis as a complication of radioembolization in our institution between 2001 and 2012 were retrospectively reviewed. Patient demographics, cancer details including treatment history, and procedural details of radioembolization and complications of cholecystitis were collected. RESULTS: Of 74 patients who underwent radioembolization using yttrium-90emitting microspheres, four (5.4%) presented with acute cholecystitis as a result of their treatment. All patients presented over 4 weeks following radioembolization and did not settle with conservative treatment. At surgery, the gallbladder was fibrotic and contracted in all cases making surgery difficult. CONCLUSION: The incidence of symptomatic radiation cholecystitis after radioembolization is low, and prophylactic cholecystectomy is not routinely recommended for patients undergoing radioembolization. Radiation cholecystitis should be suspected in patients presenting with symptoms of biliary colic or cholecystitis following radioembolization. Early cholecystectomy can be considered in patients undergoing surgery for other indications, especially in high-risk surgical patients in whom there is a high likelihood of radioembolization in the future as they do not respond to conservative treatment.


Assuntos
Colecistite Aguda/etiologia , Embolização Terapêutica/efeitos adversos , Microesferas , Radioisótopos de Ítrio/efeitos adversos , Adulto , Idoso , Colecistectomia , Colecistite Aguda/diagnóstico , Colecistite Aguda/cirurgia , Embolização Terapêutica/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Estudos Retrospectivos
20.
Expert Opin Drug Deliv ; 13(3): 401-19, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26654403

RESUMO

INTRODUCTION: Antibody-conjugated therapies (ACTs) combine the specificity of monoclonal antibodies to target cancer cells directly with highly potent payloads, often resulting in superior efficacy and/or reduced toxicity. This represents a new approach to the treatment of cancer. There have been highly promising clinical trial results using this approach with improvements in linker and payload technology. The breadth of current trials examining ACTs in haematological malignancies and solid tumours indicate the potential for clinical impact. AREAS COVERED: This review will provide an overview of ACTs currently in clinical development as well as the principles of antibody delivery and types of payloads used, including cytotoxic drugs, radiolabelled isotopes, nanoparticle-based siRNA particles and immunotoxins. EXPERT OPINION: The focus of much of the clinical activity in ACTs has, understandably, been on their use as a monotherapy or in combination with standard of care drugs. This will continue, as will the search for better targets, linkers and payloads. Increasingly, as these drugs enter routine clinical care, important questions will arise regarding how to optimise ACT treatment approaches, including investigation of resistance mechanisms, biomarker and patient selection strategies, understanding of the unique toxicities of these drugs, and combinatorial approaches with standard therapies as well as emerging therapeutic agents like immunotherapy.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia/métodos , Imunotoxinas/administração & dosagem , Neoplasias/tratamento farmacológico
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