X
Search Filters
Format Format
Subjects Subjects
Subjects Subjects
X
Sort by Item Count (A-Z)
Filter by Count
humans (24) 24
index medicus (19) 19
male (14) 14
melanoma (14) 14
female (13) 13
oncology (13) 13
middle aged (11) 11
adult (10) 10
cancer (10) 10
aged (8) 8
article (8) 8
melanoma - drug therapy (8) 8
treatment outcome (7) 7
chemotherapy (6) 6
immunotherapy (6) 6
medical research (6) 6
melanoma - pathology (6) 6
aged, 80 and over (5) 5
disease progression (5) 5
disease-free survival (5) 5
ipilimumab (5) 5
survival (5) 5
analysis (4) 4
antineoplastic agents - therapeutic use (4) 4
antineoplastic combined chemotherapy protocols - therapeutic use (4) 4
care and treatment (4) 4
cell line, tumor (4) 4
double-blind method (4) 4
drug therapy (4) 4
health aspects (4) 4
malignant-melanoma (4) 4
melanoma - genetics (4) 4
melanoma - mortality (4) 4
melanoma - secondary (4) 4
metastasis (4) 4
mutation (4) 4
neoplasm staging (4) 4
proteins (4) 4
proto-oncogene proteins b-raf - genetics (4) 4
research (4) 4
skin neoplasms - pathology (4) 4
tumors (4) 4
abridged index medicus (3) 3
adolescent (3) 3
animals (3) 3
antibodies, monoclonal - therapeutic use (3) 3
antineoplastic agents - administration & dosage (3) 3
antineoplastic agents - adverse effects (3) 3
b-raf (3) 3
biochemotherapy (3) 3
cell biology (3) 3
clinical trials (3) 3
decrescendo interleukin-2 (3) 3
disease (3) 3
double-blind (3) 3
genetic aspects (3) 3
hematology, oncology and palliative medicine (3) 3
imidazoles - administration & dosage (3) 3
kaplan-meier estimate (3) 3
lymphomas (3) 3
monoclonal antibodies (3) 3
mutations (3) 3
nivolumab (3) 3
ophthalmology (3) 3
oximes - administration & dosage (3) 3
prospective studies (3) 3
proto-oncogene proteins b-raf - antagonists & inhibitors (3) 3
skin cancer (3) 3
studies (3) 3
surgery (3) 3
young adult (3) 3
acquired-resistance (2) 2
actinomycin-d (2) 2
anatomy (2) 2
antibodies, monoclonal, humanized - administration & dosage (2) 2
antibodies, monoclonal, humanized - therapeutic use (2) 2
antigens (2) 2
antineoplastic combined chemotherapy protocols - administration & dosage (2) 2
antineoplastic combined chemotherapy protocols - adverse effects (2) 2
astigmatism (2) 2
biomarkers (2) 2
biomarkers, tumor - blood (2) 2
biomarkers, tumor - genetics (2) 2
biomarkers, tumor - metabolism (2) 2
brain neoplasms - secondary (2) 2
cell division (2) 2
cell nucleolus - metabolism (2) 2
cell nucleus - metabolism (2) 2
cellular biology (2) 2
cohort studies (2) 2
complications and side effects (2) 2
concurrent biochemotherapy (2) 2
corneal ulcer (2) 2
ctla-4 (2) 2
dictyostelium - metabolism (2) 2
discoideum (2) 2
disease models, animal (2) 2
dose-response relationship, drug (2) 2
drug administration schedule (2) 2
educational sociology (2) 2
more...
Library Location Library Location
Language Language
Publication Date Publication Date
Click on a bar to filter by decade
Slide to change publication date range


Lancet Oncology, The, ISSN 1470-2045, 2015, Volume 16, Issue 8, pp. 908 - 918
Journal Article
Lancet, The, ISSN 0140-6736, 2012, Volume 379, Issue 9829, pp. 1893 - 1901
Summary Background Dabrafenib is an inhibitor of BRAF kinase that is selective for mutant BRAF. We aimed to assess its safety and tolerability and to establish... 
Internal Medicine | SURVIVAL | IRRADIATION | MEDICINE, GENERAL & INTERNAL | PATHWAY | RAF INHIBITOR RESISTANCE | B-RAF | MUTATIONS | CANCER | BRAF(V600E) | VEMURAFENIB | Oximes - adverse effects | Humans | Middle Aged | Carcinoma, Squamous Cell - chemically induced | Oximes - administration & dosage | Imidazoles - administration & dosage | Male | Fatigue - chemically induced | Antineoplastic Agents - administration & dosage | Fever - chemically induced | Indoles - administration & dosage | Brain Neoplasms - secondary | Neoplasms - genetics | Antineoplastic Agents - adverse effects | Melanoma - genetics | Adult | Female | Drug Administration Schedule | Imidazoles - adverse effects | Genotype | Treatment Outcome | Skin Neoplasms - chemically induced | Brain Neoplasms - drug therapy | Mutation - genetics | Melanoma - secondary | Neoplasms - drug therapy | Proto-Oncogene Proteins B-raf - antagonists & inhibitors | Maximum Tolerated Dose | Indoles - adverse effects | Proto-Oncogene Proteins B-raf - genetics | Melanoma - drug therapy | Sulfonamides - adverse effects | Sulfonamides - administration & dosage | Antimitotic agents | Complications and side effects | Melanoma | Dosage and administration | Metastasis | Antineoplastic agents | Drug therapy | Clinical trials | Medical research | Chemotherapy | Mutation | Toxicity | Tumors
Journal Article
Journal Article
Journal of Immunotherapy, ISSN 1524-9557, 2017, Volume 40, Issue 9, pp. 334 - 340
KEYNOTE-030 (ClinicalTrials. gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1... 
pembrolizumab | melanoma | PD-1 | immunotherapy | expanded access program | SURVIVAL | MEDICINE, RESEARCH & EXPERIMENTAL | RESPONSE CRITERIA | IMMUNOLOGY | CANCER | UNTREATED MELANOMA | METASTATIC UVEAL MELANOMA | ONCOLOGY | ANTITUMOR IMMUNITY | ANTI-PD-1 | NIVOLUMAB | BLOCKADE | IPILIMUMAB | Basic Studies
Journal Article
Cancer Discovery, ISSN 2159-8274, 01/2018, Volume 8, Issue 1, pp. 37 - 48
Journal Article
Journal Article
The New England Journal of Medicine, ISSN 0028-4793, 08/2010, Volume 363, Issue 8, pp. 711 - 723
Journal Article
by AUTHORS and Chandni Ravi and Maureen Gang and PEER REVIEWER and Steven M Winograd, MD and The keys to identifying toxicity from checkpoint inhibitor therapy are knowing the patient has received such therapy and connecting the various symptoms and signs to one cause The toxicity from checkpoint inhibitor therapy resembles autoimmune disorders, with skin, intestinal, endocrine, and pulmonary manifestations appearing in that sequence Toxicity from adoptive cell therapy can produce the cytokine release syndrome, causing patients to present with fever, tachycardia, hypotension, and multi-organ failure The febrile neutropenic patient should be evaluated carefully for an occult bacterial infection and managed with the expectation of empiric broad-spectrum antibiotics initiated in the emergency department Scoring systems to identify low-risk patients with febrile neutropenia have not yet been prospectively validated for patients presenting to the emergency department Early consultation with the patient’s oncologist can be helpful in directing the assessment and disposition of patients with cancer therapy-related toxicity ------------ Cancer therapy has been an area of constant discovery and evolution over the past two centuries, with innovative therapeutic strategies being developed as understanding of the underlying biologic processes increases This has led to an expansion of treatment options in recent years with newer, more effective, and better-tolerated alternatives developed seemingly daily Until the early 20th century, surgical excision of tumors remained the mainstay of cancer therapy Perhaps the most influential individual to have shaped the surgical approach to cancer was William Halstead (1852-1922) through his advocacy for the en bloc resection of the tumors and enough surrounding tissue to remove all the cancer cells However, this approach was useful only for solid tumors that had not spread beyond their site of origin With the discoveries of X-rays by Roentgen and radium by Pierre and Marie Curie, radiation therapy was introduced as a second modality to combat cancer1 Nitrogen mustard, used during the first World War as an agent of chemical warfare, was noted to have destructive effects on white blood cells, and subsequently was approved by the US Food and Drug Administration (FDA) as a chemotherapeutic agent against Hodgkin lymphoma2 This marked the advent of cancer chemotherapy as an adjuvant to surgery and radiation Successful trials involving Hodgkin lymphoma and childhood leukemia using regimens such as MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) and prednisone with 6-MP (6-mercaptopurine) introduced the concepts of combination chemotherapy in the 1960s3,4 For the next several decades, surgery, radiation, and chemotherapy would remain the mainstays of cancer therapy In recent years, a paradigm shift has occurred in cancer therapeutics A vast number of newer treatment modalities are being used today, including targeted therapies, cancer vaccines, and, most recently, immunotherapy Since 2006, the FDA has approved more than 130 new cancer drugs and indications for their use5 Such major improvements in the ability to fight cancer have led to a 27% decline in death rates and increased five-year survival rates Two-thirds of people diagnosed with cancer live at least five years after diagnosis The projected population living with a cancer diagnosis is expected to grow to nearly 26 million by 2040, with 73% of survivors 65 years of age or older5,6 In turn, this increase in survivors will increase the number of emergency department (ED) visits of patients experiencing both acute and chronic complications related to cancer therapy Although emergency providers are familiar with the adverse effects of older therapies, such as neutropenic fever and tumor lysis syndrome, the rapidly changing landscape of cancer therapy requires providers not only to keep abreast of treatment guidelines for these better-known complications, but also to familiarize themselves with the newer modalities and their associated toxicities and treatment options Newer Strategies in Cancer Treatment Immuno-oncology currently is perhaps the most exciting area in cancer research and has created a paradigm shift in the management of cancer Immunotherapy works by potentiating the patient’s immune response to tumor cells, as opposed to traditional modalities that target the tumor directly7,8 Several classes of immunological agents have been developed or are being studied currently These agents include immune checkpoint inhibitors (ICIs), targeted therapies, adoptive cell immunotherapy, and cancer vaccines Immune Checkpoint Inhibitors By evading the intrinsic immune checkpoints, cancer cells can escape the immune mechanism that is supposed to eliminate the cells expressing tumor antigens9 Immune checkpoints are comprised of multiple pathways that regulate crucial steps of T-cell mediated immunity to maintain tolerance to self-antigens and prevent autoimmunity10 These pathways are initiated primarily through T-cell inhibiting and stimulating receptors and their ligands, such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1) protein, and programmed cell death ligand-1 (PD-L1)7 The upregulation of CTLA-4 or PD-1 by some tumors can suppress the immune system in fighting disease by putting brakes on T cells By acting against these receptors, checkpoint inhibitors block the immune evasion by cancer cells and encourage their destruction by the host immune system11,12 Immune checkpoint inhibitors became an area of great interest over the past decade following clinical trials demonstrating improved survival in advanced melanoma patients Previously there was no approved therapy for advanced melanoma The first agent to be studied and approved by the FDA was the anti-CTLA-4 monoclonal antibody ipilimumab13,14 Next to emerge were antibodies against PD-1 or its ligand PD-L1, which resulted in long-term responses and minimal side effects in patients with several types of cancer, including melanoma and lung, kidney, bladder, and triple-negative breast cancer and and chemotherapy-refractory Hodgkin disease11,12 Anti-PD-1 therapy was found to be superior to standard-of-care chemotherapy as well as CTLA-4 inhibition in some cases In 2014, the FDA approved pembrolizumab and nivolumab, two drugs in this class15 Several ICIs, which are approved for use in a variety of cancers, have emerged as a result of the rapid pace of ongoing research (See Table 1) A combination of CTLA-4 and PD-1 inhibitors has been associated with more favorable outcomes than with either monotherapy, leading to the development of various combination therapies15-17 In addition to cancer, researchers also are studying ICIs for their potential role in the treatment of HIV19,20 and autoimmune disease type 1 diabetes21 Emergency providers will be more likely to encounter patients receiving checkpoint inhibition therapy in the future given the growing expansion of indications for its use Mechanism of Action of Anti-CTLA-4 and Anti-PD-1 Agents An APC presents a foreign or perceived non-self-peptide fragment via its MHC, which binds and stimulates a TCR Activation of the TCR leads to expression of CTLA-4, which binds with a greater affinity to CD80/86 and promotes self-tolerance and prevents autoimmunity in normal conditions The anti-CTLA-4 therapies inhibit this co-inhibitory pathway and lead to enhanced T-cell stimulation and tumor surveillance On the right side of the figure, a similar mechanism is seen for the anti-PD-1/PD-L1 agents PD-L1 is expressed on cancer cells (among others) and also inhibits T-cell activation when binding to the PD-1 expressed on the surface of the T cell Anti-PD-1/PD-L1 treatment leads to the inhibition of this inhibitory pathway and leads to enhanced T-cell activity against tumors APC = antigen presenting cell and MHC = major histocompatibility complex and TCR = T-cell receptor Reprinted with permission from: Hryniewicki AT, Wang C, Shatsky RA, Coyne CJ Management of immune checkpoint inhibitor toxicities: A review and clinical guideline for emergency physicians J Emerg Med 2018 and