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PURPOSE: This paper aims to provide a comprehensive understanding of the need for continued development of symptom monitoring (SM) implementation, utilization, and data usage at the macro-, meso-, and micro-levels. METHODS: Discussions from a patient-reported SM workshop at the MASCC/ISSO 2022 annual meeting were analyzed using a macro-meso-micro analytical framework of cancer care delivery. The workshop categories "initiation and implementation, barriers to adoption and utilization, and data usage" were integrated for each level. RESULTS: At the macro-level, policy development could encourage data sharing and international collaboration, including the exchange of SM methods, supportive care models, and self-management modules. At the meso-level, institutions should adjust clinical workflow and service delivery and promote a thorough technical and clinical integration of SM. At the micro-level, SM should be individualized, with timely feedback for patients, and should foster trust and understanding of AI decision support tools amongst clinicians to improve supportive care. CONCLUSIONS: The workshop reached a consensus among international experts on providing guidance on SM implementation, utilization, and (big) data usage pathways in cancer survivors across the cancer continuum and on macro-meso-micro levels.
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Supervivientes de Cáncer , Humanos , Cognición , Consenso , Difusión de la Información , Medición de Resultados Informados por el PacienteRESUMEN
PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.
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Antieméticos , Antineoplásicos , Humanos , Aprepitant/uso terapéutico , Olanzapina/uso terapéutico , Cisplatino/efectos adversos , Consenso , Serotonina/efectos adversos , Antineoplásicos/uso terapéutico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Antieméticos/uso terapéutico , Dexametasona/uso terapéuticoRESUMEN
PURPOSE: Our goal was to identify new anticancer agents approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA) since the 2016 MASCC/ESMO antiemetic update and classify their emetic potential. METHODS: The MASCC/ESMO Expert Panel classified the emetogenicity of the identified new antineoplastic agents based on nonsystematic reviews of randomized controlled trials, analysis of product labeling, and evaluation of emetic classification in other international guidelines and informal consensus. The emetogenic classification system for oral anticancer agents was revised into two emetic risk categories (minimal-low; moderate-high) to be consistent with the system reported by ASCO (American Society of Clinical Oncology) in their 2017 guideline update. The previously employed four emetic risk classification categories for intravenously administered antineoplastic agents were retained for this update. RESULTS: From June 2015 to January 2023, 107 new antineoplastic agents (44 intravenously administered and 63 orally administered agents) were identified. The reported incidence of vomiting varied significantly across studies for many agents, especially for oral anticancer agents. CONCLUSION: The MASCC/ESMO Expert Panel acknowledges the limitations of our efforts to classify the emetic potential of anticancer agents, especially the imprecision associated with oral agents. However, we have attempted to provide a reasonable approximation of the emetic risk associated with new antineoplastic agents by searching the available literature and reviewing other available international antiemetic guidelines.
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Antieméticos , Antineoplásicos , Humanos , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Consenso , Eméticos/uso terapéutico , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: Review the literature to update the MASCC guidelines from 2016 for controlling nausea and vomiting with systemic cancer treatment of low and minimal emetic potential. METHODS: A working group performed a systematic literature review using Medline, Embase, and Scopus databases between June 2015 and January 2023 of the management of antiemetic prophylaxis for anticancer therapy of low or minimal emetic potential. A consensus committee reviewed recommendations and required a consensus of 67% or greater and a change in outcome of at least 10%. RESULTS: Of 293 papers identified, 15 had information about managing systemic cancer treatment regimens of low or minimal emetic potential and/or compliance with previous management recommendations. No new evidence was reported that would change the current MASCC recommendations. No antiemetic prophylaxis is recommended for minimal emetic potential therapy, and single agents recommended for low emetic potential chemotherapy for acute emesis, but no prophylaxis is recommended for delayed emesis. Commonly, rescue medication includes antiemetics prescribed for the next higher level of emesis. CONCLUSION: There is insufficient data to change the current guidelines. Future studies should seek to more accurately determine the risk of emesis with LEC beyond the emetogenicity of the chemotherapy to include patient-related risk assessment.
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Antieméticos , Antineoplásicos , Humanos , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Consenso , Eméticos , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Revisiones Sistemáticas como Asunto , Guías de Práctica Clínica como AsuntoRESUMEN
PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.
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Neutropenia Febril , Neoplasias , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Oncología Médica , Neutropenia Febril/inducido químicamente , Neutropenia Febril/epidemiología , Neutropenia Febril/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.
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Micropartículas Derivadas de Células , Neoplasias Pulmonares , Trombosis , Humanos , Plaquetas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Trombosis/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinogénesis/metabolismo , Progresión de la EnfermedadRESUMEN
Triple-negative breast cancer (TNBC) has the highest rate of distant metastasis and poorest overall survival among breast cancer subtypes. In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability.
Patients with triple-negative breast cancer generally do very poorly with the current available therapies. A vaccine with a totally different mechanism of action is being investigated in these patients to see how they do with this new therapy. This trial is a very early investigation and is currently ongoing. Clinical Trial Registration: NCT03562637 (ClinicalTrials.gov).
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PURPOSE OF REVIEW: The past decade has witnessed unprecedented delivery to the clinical arena of a range of novel, innovative, and effective targeted anticancer therapies. These include immunotherapies, most prominently immune checkpoint inhibitors, as well as agents that target growth factors and cancer-related mutations. Many of these new cancer therapies are, however, associated with an array of toxicities, necessitating insight and vigilance on the part of attending physicians to achieve high-quality supportive care alongside toxicity management. In this review, we consider some of the key supportive care issues in toxicity management. RECENT FINDINGS: Although both supportive care and targeted therapies have brought significant benefits to cancer care, the management of novel cancer therapy toxicities is nevertheless often complex. This is due in large part to the fact that target organs differ widely, particularly in the case of checkpoint inhibitors, with minor dermatological disorders being most common, while others, such as pneumonitis, are more severe and potentially life threatening. Accordingly, efficient management of these immune-related adverse events requires collaboration between multiple medical specialists. SUMMARY: Supportive care is a key component in the management of new cancer therapy toxicities and needs to be incorporated into treatment pathways.
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Neoplasias/terapia , Cuidados Paliativos/métodos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Humanos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológicoRESUMEN
Patients with cancer are at higher risk of more severe COVID-19 infection and have more associated complications. The position paper describes the management of cancer patients, especially those receiving anticancer treatment, during the COVID-19 pandemic. Dyspnea is a common emergency presentation in patients with cancer with a wide range of differential diagnoses, including pulmonary embolism, pleural disease, lymphangitis, and infection, of which SARS-CoV-2 is now a pathogen to be considered. Screening interviews to determine whether patients may be infected with COVID-19 are imperative to prevent the spread of infection, especially within healthcare facilities. Cancer patients testing positive with no or minimal symptoms may be monitored from home. Telemedicine is an option to aid in following patients without potential exposure. Management of complications of systemic anticancer treatment, such as febrile neutropenia (FN), is of particular importance during the COVID-19 pandemic where clinicians aim to minimize patients' risk of infection and need for hospital visits. Outpatient management of patients with low-risk FN is a safe and effective strategy. Although the MASCC score has not been validated in patients with suspected or confirmed SARS-CoV-2, it has nevertheless performed well in patients with a range of infective illnesses and, accordingly, it is reasonable to expect efficacy in the clinical setting of COVID-19. Risk stratification of patients presenting with FN is a vital tenet of the evolving sepsis and pandemic strategy, necessitating access to locally formulated services based on MASCC and other national and international guidelines. Innovative oncology services will need to utilize telemedicine, hospital at home, and ambulatory care services approaches not only to limit the number of hospital visits but also to anticipate the complications of the anticancer treatments.
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COVID-19/diagnóstico , Neutropenia Febril/diagnóstico , Fiebre/etiología , Neoplasias/complicaciones , Atención Ambulatoria , COVID-19/complicaciones , Neutropenia Febril/etiología , Neutropenia Febril/terapia , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Pandemias , SARS-CoV-2 , TelemedicinaRESUMEN
BACKGROUND: Results from a phase III, randomized, double-blind, active comparator-controlled, parallel-group trial evaluating fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) found that a single-day, triple-antiemetic fosaprepitant regimen resulted in a significantly higher proportion of patients achieving a complete response (CR; no vomiting or rescue medication use) in the delayed phase (25-120 h after chemotherapy initiation), compared with a 3-day control regimen ( ClinicalTrials.gov , NCT01594749). As the risk for CINV is dependent on chemotherapy regimen and generally guided by tumor type, this post hoc analysis evaluated the efficacy and safety of this regimen by cancer subpopulations (gastrointestinal [GI] or colorectal, lung, breast, and gynecologic cancers). METHODS: Subjects with confirmed cancer who were naive to highly and moderately emetogenic chemotherapy (HEC and MEC) and were scheduled to receive intravenous (IV) anthracycline-cyclophosphamide (AC)-based MEC on the first day of chemotherapy were randomly assigned to receive oral ondansetron and oral dexamethasone plus either a single IV dose of fosaprepitant 150 mg (fosaprepitant regimen) or placebo (control regimen). The primary efficacy end point was the proportion of subjects achieving CR in the delayed phase. CR rates in the overall and acute phases (0-120 h and 0-24 h after MEC initiation, respectively) were assessed as secondary end points. Safety and tolerability were also assessed. RESULTS: CR rates in the delayed phase favored the fosaprepitant regimen over the control regimen across the GI/colorectal, lung, breast, and gynecologic cancer subgroups (range, 6.2-22%); similar findings were observed for CR in the overall phase. CR in the acute phase was high for all groups (≥87%). The fosaprepitant regimen was well tolerated in all cancer subgroups. CONCLUSIONS: This post hoc analysis indicated that a single-day fosaprepitant regimen was effective in preventing CINV in patients receiving MEC, regardless of cancer type. TRIAL REGISTRATION: ClinicalTrials.gov NCT01594749 , registered May 9, 2012.
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Antieméticos/uso terapéutico , Morfolinas/uso terapéutico , Náusea/tratamiento farmacológico , Neoplasias/complicaciones , Vómitos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/farmacología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/farmacología , Náusea/inducido químicamente , Vómitos/inducido químicamente , Adulto JovenRESUMEN
Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.
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Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/patología , Historia del Siglo XXI , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Agencias Internacionales/organización & administración , Agencias Internacionales/normas , Cuidados Paliativos/organización & administración , Cuidados Paliativos/normas , Medicina Paliativa/organización & administración , Medicina Paliativa/normas , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Índice de Severidad de la Enfermedad , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.
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Antineoplásicos Inmunológicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Oncología Médica/métodos , Oncología Médica/tendencias , Neoplasias/epidemiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
The immune checkpoints associated with the CTLA-4 and PD-1 pathways are critical modulators of immune activation. These pathways dampen the immune response by providing brakes on activated T cells, thereby ensuring more uniform and controlled immune reactions and avoiding immune hyper-responsiveness and autoimmunity. Cancer cells often exploit these regulatory controls through a variety of immune subversion mechanisms, which facilitate immune escape and tumor survival. Immune checkpoint inhibitors (ICI) effectively block negative regulatory signals, thereby augmenting immune attack and tumor killing. This process is a double-edged sword in which release of regulatory controls is felt to be responsible for both the therapeutic efficacy of ICI therapy and the driver of immune-related adverse events (IrAEs). These adverse immune reactions are common, typically low-grade and may affect virtually every organ system. In the early clinical trials, lung IrAEs were rarely described. However, with ever-expanding clinical applications and more complex ICI-containing regimens, lung events, in particular, pneumonitis, have become increasingly recognized. ICI-related lung injury is clinically distinct from other types of lung toxicity and may lead to death in advanced stage disease. Thus, knowledge regarding the key characteristics and optimal treatment of lung-IrAEs is critical to good outcomes. This review provides an overview of lung-IrAEs, including risk factors and epidemiology, as well as clinical, radiologic, and histopathologic features of ICI-related lung injury. Management principles for ICI-related lung injury, including current consensus on steroid refractory pneumonitis and the use of other immune modulating agents in this setting are also highlighted.
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Factores Inmunológicos/efectos adversos , Inmunoterapia/efectos adversos , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/terapia , Neoplasias/terapia , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Historia del Siglo XXI , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/uso terapéutico , Agencias Internacionales/organización & administración , Agencias Internacionales/normas , Enfermedades Pulmonares/epidemiología , Cuidados Paliativos/organización & administración , Cuidados Paliativos/normas , Medicina Paliativa/organización & administración , Medicina Paliativa/normas , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Índice de Severidad de la Enfermedad , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Immune checkpoint inhibitors (ICIs) frequently result in cutaneous immune-related adverse events (IrAEs). Although the majority of these events are mild-to-moderate in severity, up to 5% are severe, which may lead to morbidity and dose interruption or discontinuation of ICI therapy. In addition, up to 25% of dermatologic IrAEs are corticosteroid-refractory or corticosteroid-dependent. These 2020 MASCC recommendations cover the diagnosis and management of cutaneous IrAEs with a focus on moderate-to-severe and corticosteroid-resistant events. Although the usage of immune-suppressive therapy has been advocated in this setting, there is a lack of randomized clinical trial data to provide a compelling level of evidence of its therapeutic benefit.
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Erupciones por Medicamentos/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/terapia , Cuidados Paliativos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Historia del Siglo XXI , Humanos , Inmunoterapia/efectos adversos , Agencias Internacionales/organización & administración , Agencias Internacionales/normas , Neoplasias/inmunología , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Medicina Paliativa/organización & administración , Medicina Paliativa/normas , Índice de Severidad de la Enfermedad , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Although they are of variable occurrence, cardiovascular, rheumatic, and renal immune-mediated toxicities are among the most serious of these adverse events. We present MASCC recommendations with respect to the workup and management of cardiovascular, rheumatic, and renal immune-mediated toxicities with a focus on presentations that require treatment with immunomodulating agents.
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Enfermedades Cardiovasculares/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Enfermedades Renales/terapia , Enfermedades Reumáticas/terapia , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Historia del Siglo XXI , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Agencias Internacionales/organización & administración , Agencias Internacionales/normas , Enfermedades Renales/inducido químicamente , Enfermedades Renales/epidemiología , Neoplasias/epidemiología , Neoplasias/inmunología , Neoplasias/terapia , Cuidados Paliativos/organización & administración , Cuidados Paliativos/normas , Medicina Paliativa/organización & administración , Medicina Paliativa/normas , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Enfermedades Reumáticas/inducido químicamente , Enfermedades Reumáticas/epidemiología , Índice de Severidad de la Enfermedad , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment, transforming outcomes in melanoma and showing benefit in a range of malignancies. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Immune-mediated endocrinopathies include hypophysitis, thyroiditis, and insulin-dependent diabetes mellitus. These presentations, which may be vague and non-specific, can be life-threatening if not diagnosed and treated appropriately. This review considers the work-up and management of immune-mediated endocrinopathies and also considers the role of advanced practice practitioners in the management of immune-mediated toxicities. These state-of-the-art MASCC recommendations represent a comprehensive overview of the management and clinical work-up in those in whom the diagnosis should be considered.
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Enfermedades del Sistema Endocrino/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Rol del Médico , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/epidemiología , Historia del Siglo XXI , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Agencias Internacionales/organización & administración , Agencias Internacionales/normas , Oncología Médica/organización & administración , Oncología Médica/normas , Neoplasias/epidemiología , Neoplasias/inmunología , Cuidados Paliativos/organización & administración , Cuidados Paliativos/normas , Medicina Paliativa/organización & administración , Medicina Paliativa/normas , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Índice de Severidad de la Enfermedad , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Notwithstanding the well-recognized involvement of chronic neutrophilic inflammation in the initiation phase of many types of epithelial cancers, a growing body of evidence has also implicated these cells in the pathogenesis of the later phases of cancer development, specifically progression and spread. In this setting, established tumors have a propensity to induce myelopoiesis and to recruit neutrophils to the tumor microenvironment (TME), where these cells undergo reprogramming and transitioning to myeloid-derived suppressor cells (MDSCs) with a pro-tumorigenic phenotype. In the TME, these MDSCs, via the production of a broad range of mediators, not only attenuate the anti-tumor activity of tumor-infiltrating lymphocytes, but also exclude these cells from the TME. Realization of the pro-tumorigenic activities of MDSCs of neutrophilic origin has resulted in the development of a range of adjunctive strategies targeting the recruitment of these cells and/or the harmful activities of their mediators of immunosuppression. Most of these are in the pre-clinical or very early clinical stages of evaluation. Notable exceptions, however, are several pharmacologic, allosteric inhibitors of neutrophil/MDSC CXCR1/2 receptors. These agents have entered late-stage clinical assessment as adjuncts to either chemotherapy or inhibitory immune checkpoint-targeted therapy in patients with various types of advanced malignancy. The current review updates the origins and identities of MDSCs of neutrophilic origin and their spectrum of immunosuppressive mediators, as well as current and pipeline MDSC-targeted strategies as potential adjuncts to cancer therapies. These sections are preceded by a consideration of the carcinogenic potential of neutrophils.
Asunto(s)
Susceptibilidad a Enfermedades , Neoplasias/etiología , Neoplasias/metabolismo , Neutrófilos/inmunología , Neutrófilos/metabolismo , Animales , Transformación Celular Neoplásica , Manejo de la Enfermedad , Interacciones Huésped-Patógeno , Humanos , Inmunomodulación , Inflamación/complicaciones , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neutrófilos/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo , Resultado del TratamientoRESUMEN
Aim: This meta-analysis compared incidence of grade 3-4 neutropenia with ALK inhibitors versus chemotherapy in patients with non-small-cell lung cancer. Materials & methods: PubMed/MEDLINE was searched to identify Phase II and III randomized clinical trials published up to 25 October 2018. Summary incidence, relative risk and corresponding 95% CIs were calculated for grade 3-4 neutropenia. Results: Five randomized clinical trials were included. Relative risk (95% CI) of developing grade 3-4 neutropenia with ALK inhibitor versus chemotherapy was 0.27 (0.07-1.06). Probabilities of developing grade 3-4 neutropenia were 6.56 and 14.19%, respectively; no significant difference was found. Conclusion: In patients with non-small-cell lung cancer, incidence of grade 3-4 neutropenia with ALK-targeted therapy is not significantly different compared with chemotherapy.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Inhibidores de Proteínas Quinasas/efectos adversos , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Sesgo de Publicación , Índice de Severidad de la EnfermedadRESUMEN
Immunogenic cell death (ICD), which is triggered by exposure of tumor cells to a limited range of anticancer drugs, radiotherapy, and photodynamic therapy, represents a recent innovation in the revitalized and burgeoning field of oncoimmunnotherapy. ICD results in the cellular redistribution and extracellular release of damage-associated molecular patterns (DAMPs), which have the potential to activate and restore tumor-targeted immune responses. Although a convincing body of evidence exists with respect to the antitumor efficacy of ICD in various experimental systems, especially murine models of experimental anticancer immunotherapy, evidence for the existence of ICD in the clinical setting is less compelling. Following overviews of hallmark developments, which have sparked the revival of interest in the field of oncoimmunotherapy, types of tumor cell death and the various DAMPs most prominently involved in the activation of antitumor immune responses, the remainder of this review is focused on strategies which may potentiate ICD in the clinical setting. These include identification of tumor- and host-related factors predictive of the efficacy of ICD, the clinical utility of combinatorial immunotherapeutic strategies, novel small molecule inducers of ICD, novel and repurposed small molecule immunostimulants, as well as the critical requirement for validated biomarkers in predicting the efficacy of ICD.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Radioterapia , Alarminas/metabolismo , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de la radiación , Humanos , Neoplasias/inmunología , Neoplasias/radioterapiaRESUMEN
BACKGROUND: Febrile neutropenia (FN) is a common occurrence during chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSF for patients receiving chemotherapy with FN risk of ≥20% or 10% to 20% with defined risk factors. Prophylaxis is not typically recommended for FN risk of < 10%; however, few studies have investigated FN incidence in lower-risk patients in real-world settings and tried to identify higher-risk subgroups. METHODS: This real-world prospective, observational, multinational study aims to estimate the rate of development of FN with a chemotherapy line expected to be associated with a 10% to 20% risk of FN. Eligible patients (> 18 years of age) will have a solid tumour or Hodgkin/non-Hodgkin lymphoma and a planned chemotherapy regimen with expected risk of FN of 10% to 20% (according to published guidelines). Patients will be observed for the duration of the chemotherapy line (first cycle administered without FN prophylaxis). Primary endpoint is incidence of FN after the first chemotherapy cycle. Secondary outcomes include: FN-associated morbidity and mortality; time to first FN occurrence; other FN risk factors and impact of FN on quality of life. A risk model using occurrence of FN as a binary outcome will be developed. Data will be stratified by age, comorbidities and other risk factors. DISCUSSION: This study will provide insight into the real FN risk for common chemotherapy regimens and predictive factors for FN, including patients generally excluded from randomised clinical trials, from which reported FN rates have been variable. This study builds on knowledge of predictive factors from other research and will provide information on patients with 10% to 20% FN risk.