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1.
Eur J Cancer Care (Engl) ; 30(3): e13408, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33474755

RESUMEN

OBJECTIVE: Few teenagers and young adults (TYA) with cancer participate in clinical trials. Lack of opportunity has been identified as a major barrier. We canvassed health professionals' views on how TYA's access to trials might be improved. METHODS: We interviewed 35 professionals with responsibility for delivering or facilitating cancer care and/or clinical trials. We analysed data using a qualitative descriptive approach. RESULTS: Interviewees viewed improving TYA's access to trials as challenging, but possible. They reframed the problem as one of rare disease and surmised that modifying the organisation, administration and resourcing of research (and care) might expand opportunities for both TYA and other patients with low volume conditions. Proposals coalesced around four themes: consolidating the pool of patients; streamlining bureaucratic requirements; investing in the research workforce; and promoting pragmatism in trial design. CONCLUSION: Accounts suggest there is scope to improve access to trials by TYA with cancer and other patients with rare diseases. Though re-configuring care, research and resource frameworks would present substantial challenges, doing nothing would also have costs. Change will require the support of a range of stakeholders, and agreement as to the best way forward. Further work, such as priority setting exercises, may be necessary to reach a consensus.


Asunto(s)
Ensayos Clínicos como Asunto , Accesibilidad a los Servicios de Salud , Neoplasias , Adolescente , Consenso , Personal de Salud , Humanos , Neoplasias/terapia , Investigación Cualitativa , Adulto Joven
2.
BMC Health Serv Res ; 20(1): 25, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31914994

RESUMEN

BACKGROUND: Limited attention has been paid to adolescents and young adults' (AYA's) experiences in the aftermath of a cancer diagnosis, despite this being a time when potentially life-changing decisions are made. We explored AYA's and caregivers' experiences of, and views about, making treatment and trial participation decisions following a cancer diagnosis, in order to understand, and help facilitate, informed treatment decision-making in this age group. METHODS: Interviews were undertaken with 18 AYA diagnosed, or re-diagnosed, with cancer when aged 16-24 years, and 15 parents/caregivers. Analysis focused on the identification and description of explanatory themes. RESULTS: Most AYA described being extremely unwell by the time of diagnosis and, consequently, experiencing difficulties processing the news. Distress and acceleration in clinical activity following diagnosis could further impede the absorption of treatment-relevant information. After referral to a specialist cancer unit, many AYA described quickly transitioning to a calm and pragmatic mind-set, and wanting to commence treatment at the earliest opportunity. Most reported seeing information about short-term side-effects of treatment as having limited relevance to their recovery-focused outlook at that time. AYA seldom indicated wanting to make choices about front-line treatment, with most preferring to defer decisions to health professionals. Even when charged with decisions about trial participation, AYA reported welcoming a strong health professional steer. Parents/caregivers attempted to compensate for AYA's limited engagement with treatment-relevant information. However, in seeking to ensure AYA received the best treatment, these individuals had conflicting priorities and information needs. CONCLUSION: Our study highlights the challenging context in which AYA are confronted with decisions about front-line treatment, and reveals how their responses make it hard to ensure their decisions are fully informed. It raises questions about the direct value, to AYA, of approaches that aim to promote decision-making by improving understanding and recall of information, though such approaches may be of value to caregivers. In seeking to improve information-giving and involvement in treatment-related decision-making at diagnosis, care should be taken not to delegitimize the preference of many AYA for a directive approach from trusted clinicians.


Asunto(s)
Cuidadores/psicología , Toma de Decisiones , Neoplasias/terapia , Participación del Paciente/psicología , Sujetos de Investigación/psicología , Adolescente , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Investigación Cualitativa , Adulto Joven
3.
Blood ; 115(11): 2241-50, 2010 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-20068223

RESUMEN

Chronic myeloid leukemia (CML) is treated effectively with tyrosine kinase inhibitors (TKIs); however, 2 key problems remain-the insensitivity of CML stem and progenitor cells to TKIs and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and proteasome inhibitors (PIs) are cytotoxic against CML cell lines. We demonstrate that bortezomib is antiproliferative and induces apoptosis in chronic phase (CP) CD34+ CML cells at clinically achievable concentrations. We also show that bortezomib targets primitive CML cells, with effects on CD34+38(-), long-term culture-initiating (LTC-IC) and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells. Bortezomib is not selective for CML cells and induces apoptosis in normal CD34+38(-) cells. The effects against CML cells are seen when bortezomib is used alone and in combination with dasatinib. Bortezomib causes proteasome but not BCR-ABL inhibition and is also effective in inhibiting proteasome activity and inducing apoptosis in cell lines expressing BCR-ABL mutations, including T315I. By targeting both TKI-insensitive stem and progenitor cells and TKI-resistant BCR-ABL mutations, we believe that bortezomib offers a potential therapeutic option in CML. Because of known toxicities, including myelosuppression, the likely initial clinical application of bortezomib in CML would be in resistant and advanced disease.


Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Borónicos/farmacología , Técnicas de Cultivo de Célula/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Pirazinas/farmacología , Animales , Antígenos CD34/metabolismo , Bortezomib , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dasatinib , Sinergismo Farmacológico , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Ratones , Ratones SCID , Proteínas Mutantes/metabolismo , Inhibidores de Proteasoma , Pirimidinas/farmacología , Tiazoles/farmacología , Factores de Tiempo , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Blood ; 111(10): 5252-5, 2008 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-18378854

RESUMEN

Patients with newly diagnosed chronic phase chronic myeloid leukemia were treated with imatinib mesylate (IM) for 6 to 12 months to establish disease control, before reduced intensity stem cell transplantation (RISCT). Escalating doses of donor lymphocyte infusions were given from 6 months after transplantation to eradicate residual disease. A total of 18 patients entered the study and 15 received RISCT (median follow-up, 31 months). RISCT was well tolerated with rapid engraftment, short inpatient stays, and few readmissions. Viral reactivation was common, although extensive graft-versus-host disease occurred infrequently. Donor lymphocyte infusions were given as part of the RISCT protocol in 13 of 15 patients. BCR-ABL transcripts continued to decrease after RISCT, and 8 (53%) patients achieved sustained undetectable levels. All patients are currently off IM. Although IM is now established as first-line therapy for chronic phase chronic myeloid leukemia, this protocol is a safe, well-tolerated, and effective strategy in these patients. This study is registered at http://www.controlled-trials.com as ISRCTN86187144.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Transfusión de Linfocitos/métodos , Adulto , Benzamidas , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Humanos , Mesilato de Imatinib , Tiempo de Internación , Persona de Mediana Edad , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Resultado del Tratamiento , Activación Viral
5.
Blood Rev ; 24(1): 1-9, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20005615

RESUMEN

The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that targets the BCR-ABL protein, has revolutionised the treatment of chronic myeloid leukaemia (CML), producing high rates of response that have been durable in many patients. However, because of intrinsic or acquired mechanisms of imatinib resistance, in addition to the persistence of leukaemic stem cells that are resistant to imatinib-induced apoptosis, imatinib treatment does not appear to be curative. Cytogenetic and molecular monitoring enable the identification of patients showing signs of treatment failure and can be used to guide choices regarding subsequent therapeutic options, including imatinib dose escalation, treatment with a secondary TKI or, in selected cases, allogeneic stem cell transplant (allo-SCT). Although these alternative therapies may overcome imatinib resistance, long-term remission or cure from CML is likely to require development of novel interventions that effectively eliminate CML stem cells (Ph+HSC).


Asunto(s)
Resistencia a Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Manejo de la Enfermedad , Monitoreo de Drogas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Proteínas Tirosina Quinasas/antagonistas & inhibidores
6.
Hematol Oncol ; 25(2): 66-75, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17441215

RESUMEN

Chronic myeloid leukaemia (CML) is a clonal disorder of the haemopoietic stem cell arising as a consequence of the formation of the bcr-abl oncogene. The particular molecular basis of this condition has enabled the development of therapies that selectively target diseased cells. The success of the rationally designed first-line therapy imatinib mesylate (IM) is tempered by the problems of disease persistence and resistance. Novel strategies have been identified to take forward therapy in CML and these will be discussed in this review. This work is generated from a review of published literature and contains particular insight into the work performed by our group in this field.


Asunto(s)
Antineoplásicos/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Proteínas de Fusión bcr-abl/metabolismo , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Trasplante de Células Madre Hematopoyéticas , Humanos , Mesilato de Imatinib , Proteínas de Neoplasias/antagonistas & inhibidores , Piperazinas/uso terapéutico , Complejo de la Endopetidasa Proteasomal/fisiología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/uso terapéutico
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