RESUMO
The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Cetoconazol/uso terapêutico , Oligopeptídeos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Testosterona/metabolismoRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs. METHODS: We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors. RESULTS: Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes. CONCLUSIONS: Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.
Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Miocardite/induzido quimicamente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
An 84-year-old man with a history of deep vein thrombosis on warfarin and coronary artery disease presented with haematochezia and was diagnosed with an ascending colon cancer. He was short of breath with lower extremity oedema at the initial surgical consultation. Evaluation revealed an acute exacerbation of congestive heart failure, and further workup and treatment were recommended by the cardiology team. After multidisciplinary discussion, he underwent radiation for the control of bleeding, followed by cardiac catheterisation and placement of a bare metal stent. The patient subsequently underwent robotic-assisted right hemicolectomy. Pathology demonstrated a complete response, and the patient recovered uneventfully. He is alive swith no evidence of disease recurrence 12 months after surgery and 18 months after initial diagnosis.
Assuntos
Neoplasias do Colo/diagnóstico , Insuficiência Cardíaca , Idoso de 80 Anos ou mais , Colectomia , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/terapia , Terapia Combinada , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Terapia Neoadjuvante , Equipe de Assistência ao Paciente , Stents , Tomografia Computadorizada por Raios XRESUMO
The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.
RESUMO
BACKGROUND: Hypertension (HT) is a common complication of anti-angiogenic therapy. Its incidence, treatment and complications are undefined. PATIENTS AND METHODS: Retrospective review of patients treated with bevacizumab (BV) from 2003-5. Common toxicity criteria (CTC) for adverse events version 3.0 were used. RESULTS: Fifty-five out of the 154 patients treated with BV (35%) experienced HT. Eleven (20%) developed a new onset HT and 44 (80%) experienced an exacerbation of pre-existing HT. HT developed after a median of 11 weeks at a median BV dose of 10 mg/kg. HT severity was grade 1 (n =1), grade 2 (n=29) or grade 3 (n=22); 3 experienced hypertensive complications. HT was controlled in 47 (85%); BV was discontinued in 3. The angiotensin-converting enzyme inhibitor (ACE-I), quinapril was commonly used and resulted in better HT control than ACE-II, calcium channel or beta antagonists. CONCLUSION: HT associated with bevacizumab therapy is a manageable toxicity with the use of ACE-I.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Hipertensão/induzido quimicamente , Neovascularização Patológica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Bevacizumab , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Estados Unidos/epidemiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Anthracyclines constitute the backbone of intensive adult acute myeloid leukemia (AML) therapy. Cardiotoxicity is one of its most serious adverse effects, and its incidence increases with cumulative dose. Dexrazoxane is a cardioprotective agent used in conjunction with anthracycline therapy. There is limited data of its usage in adult AML patients. We report the outcomes of six older adults at high risk of anthracycline-induced cardiotoxicity who received dexrazoxane during induction/re-induction therapy. Five had preserved left-ventricular function while two proceeded onto stem-cell transplantation. Additional investigation of dexrazoxane in adult leukemia therapy is warranted, particularly in older patients at highest risk for cardiovascular mortality.
Assuntos
Cardiotoxinas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Adulto , Benzamidas , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Dasatinibe , Evolução Fatal , Feminino , Humanos , Mesilato de Imatinib , Cromossomo Filadélfia , Piperazinas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirimidinas/efeitos adversos , Tiazóis/efeitos adversosRESUMO
Cancer therapeutics is undergoing a revolution with the advent of new drugs that can selectively target molecules responsible for carcinogenesis and tumor growth. The type and mechanism of these targeting drugs vary. Some are small molecules that specifically target a binding site on a receptor or signal transduction molecule. Antibodies have been engineered to bind to the receptors or the corresponding ligands that mediate a critical cancer activity. In almost all cases, the intent is to inhibit or shut down a specific molecular pathway. Unprecedented activity against the cancer is seen without overt traditional toxicities such as alopecia, nausea and/or vomiting, and cytopenias. Unfortunately, an increase in toxicity has now become evident as more experience accumulates with the use of these drugs. In some cases, unexpected cardiotoxicities have arisen when these new drugs have been added to more conventional chemotherapies. Heart failure is the unfortunate manifestation for many of these toxicities. We outline the scope of this problem and examine the mechanisms of drug-induced heart failure. The distinctive signs and symptoms specific to each drug are described, and the diagnosis and treatment of the condition are discussed. Our aim is to allow the practitioner to recognize the unusual manifestations of heart failure in this setting in order to make a timely diagnosis and begin appropriate treatment measures.