keyword
MENU ▼
Read by QxMD icon Read
search

Carfilzomib

keyword
https://www.readbyqxmd.com/read/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#1
Morie A Gertz
: Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28092421/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-heavily-pretreated-multiple-myeloma-a-phase-1-study-in-japan
#2
Kenshi Suzuki, Masaki Ri, Takaaki Chou, Isamu Sugiura, Naoki Takezako, Kazutaka Sunami, Tadao Ishida, Tohru Izumi, Shuji Ozaki, Yoshihisa Shumiya, Kenji Ota, Shinsuke Iida
This is the first study in which the carfilzomib, lenalidomide, and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM). The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m(2) , followed by 27 mg/m(2) ...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28075552/nanoparticles-coated-with-neutrophil-membranes-can-effectively-treat-cancer-metastasis
#3
Ting Kang, Qianqian Zhu, Dan Wei, Jingxian Feng, Jianhui Yao, Tianze Jiang, Qingxiang Song, Xunbin Wei, Hong-Zhuan Chen, Xiaoling Gao, Jun Chen
The dissemination, seeding and colonization of circulating tumor cells (CTC) serves as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTC in the (pre-) metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly (latic-co-glycolic acid) nanoparticles (NP)...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28061991/combination-therapy-for-fit-younger-and-older-newly-diagnosed-multiple-myeloma-patients-data-support-carfilzomib-lenalidomide-and-dexamethasone-independent-of-cytogenetic-risk-status
#4
REVIEW
Ola Landgren
In this invited paper, I was asked to critically review available literature and seek scientific and clinical evidence to argue in support of carfilzomib, lenalidomide, and dexamethasone (KRd) as the new default therapy for fit patients with a new diagnosis of multiple myeloma (MM). When performing the review of existing data and when writing this paper it became clear to me that both KRd and bortezomib, lenalidomide, and dexamethasone (RVd) are both recommended by established, well-respected expert guidelines...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28061990/treatment-of-newly-diagnosed-myeloma-bortezomib-based-triplet
#5
REVIEW
Archana M Rajan, S Vincent Rajkumar
We review the options for the treatment of newly diagnosed myeloma in a patient who is a candidate for autologous stem cell transplantation (ASCT). Bortezomib, lenalidomide, dexamethasone (VRD) has been studied in two randomized trials as first-line therapy. In one of these trials, VRD demonstrated improved overall survival compared with lenalidomide plus dexamethasone (Rd). By contrast, phase III data with overall survival differences are not available for other bortezomib-containing regimens compared with modern lenalidomide-containing regimens...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28061984/controversies-in-multiple-myeloma-evidence-based-update
#6
REVIEW
Inhye E Ahn, Sham Mailankody
The US Food and Drug Administration (FDA) approved 10 new drugs for the treatment of multiple myeloma (MM) over the last two decades. The influx of new anti-myeloma agents with high efficacy and acceptable tolerability add complexity to the clinical decision-making process. First, treatment of smoldering multiple myeloma (SMM) remains investigational to date, although a randomized trial showed a survival gain in high-risk patients receiving lenalidomide. Second, in newly diagnosed MM, the majority of contemporary induction regimens have been studied in single-arm trials or compared to an older regimen, which complicates evidence-based treatment selection...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28043164/current-treatment-options-and-investigational-drugs-for-waldenstrom-s-macroglobulinemia
#7
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM...
January 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28040131/carfilzomib-induces-g2-m-cell-cycle-arrest-in-human-endometrial-cancer-cells-via-upregulation-of-p21-waf1-cip1-and-p27-kip1
#8
Yuanyuan Zhou, Ke Wang, Shuai Zhen, Ruili Wang, Wenjuan Luo
OBJECTIVE: Carfilzomib is a second-generation tetrapeptide epoxyketone proteasome inhibitor used in current clinical therapy of hematologic malignancies. The mechanism of proteasome inhibition in endometrial cancer is not very clear. Carfilzomib inhibition of type I endometrial carcinoma cell proliferation by inducing cell cycle arrest at the G2/M phase was investigated in our study. MATERIALS AND METHODS: HEC-1-A and Ishikawa endometrial carcinoma cell lines and three tumor cell lines were treated by different concentrations of carfilzomib...
December 2016: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28027531/exploration-of-novel-piperazine-or-piperidine-constructed-non-covalent-peptidyl-derivatives-as-proteasome-inhibitors
#9
Rangxiao Zhuang, Lixin Gao, Xiaoqing Lv, Jianjun Xi, Li Sheng, Yanmei Zhao, Ruoyu He, Xiaobei Hu, Yidan Shao, Xuwang Pan, Shourong Liu, Weiwei Huang, Yubo Zhou, Jia Li, Jiankang Zhang
A series of novel piperazine or piperidine-containing non-covalent peptidyl derivatives possessing a neopentyl-asparagine residue were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were screened for their 20S proteasome chymotrypsin-like inhibitory activities, and 15 ones displayed more potent activities than carfilzomib with IC50 values lower than 10 nM. Subsequently, the most potent 10 analogues were tested for their cytotoxic activities against two multiple myeloma (MM) cell lines RPMI-8226 and MM-1S...
December 18, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28025582/carfilzomib-dexamethasone-vs-bortezomib-dexamethasone-in-relapsed-or-refractory-multiple-myeloma-by-cytogenetic-risk-in-the-phase-3-study-endeavor
#10
W-J Chng, H Goldschmidt, M A Dimopoulos, P Moreau, D Joshua, A Palumbo, T Facon, H Ludwig, L Pour, R Niesvizky, A Oriol, L Rosiñol, A Suvorov, G Gaidano, T Pika, K Weisel, V Goranova-Marinova, H H Gillenwater, N Mohamed, S Feng, S Aggarwal, R Hájek
The randomized phase 3 study ENDEAVOR demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (MM). We conducted a preplanned subgroup analysis of ENDEAVOR to evaluate Kd vs Vd by cytogenetic risk. Of 785 patients with known cytogenetics, 210 (27%) had high-risk cytogenetics (Kd, n=97 [25%]; Vd, n=113 [28%]) and 575 (73%) had standard-risk cytogenetics (Kd, n=284 [75%]; Vd, n=291 [72%])...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28007565/mechanism-of-degradation-of-an-%C3%AE-keto-epoxide-a-model-for-the-warhead-for-various-proteasome-inhibitor-anticancer-agents
#11
Kirsten M Phizackerley, Mouhannad Jumaa, Antonio Lopalco, Bradley H Wolfe, Christopher D Ablan, Valentino J Stella
The anti-cancer agent, carfilzomib has a unique α-keto-epoxide warhead. The model α-keto-epoxide, N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)pivalamide (1) along with a few of its degradation products were synthesized and studied. The kinetics of hydrolysis and identification of some of the degradation products of 1 were performed at pH values 2, 4, 5, 7 and 8 at 25°C, 40°C and 60°C and followed by HPLC and LC-MS, respectively. 1 degraded independent of pH between pH values 4 to 7 but showed some acid catalysis at pH 2 and base catalysis at pH 8...
December 19, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27994734/new-peptidomimetic-boronates-for-selective-inhibition-of-the-chymotrypsin-like-activity-of-the-26s-proteasome
#12
Xiaozhou Zhang, Alaknanda Adwal, Andrew G Turner, David F Callen, Andrew D Abell
Proteasome is a large proteinase complex that degrades proteins via its three catalytic activities. Among these activities, the "chymotrypsin-like" activity has emerged as the focus of drug discovery in cancer therapy. Here, we report new peptidomimetic boronates that are highly specific for the chymotrypsin-like catalytic activity of the proteasome. These new specific proteasome inhibitors were demonstrated to have higher in vitro potency and selective cytotoxicity for cancer cells compared to benchmark proteasome inhibitors: bortezomib and carfilzomib...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27986429/practical-considerations-in-managing-relapsed-multiple-myeloma
#13
REVIEW
Amit Agarwal, Eric Chow, Manisha Bhutani, Peter M Voorhees, Reed Friend, Saad Z Usmani
Considerable advances have been made in the treatment of relapsed and relapsed/refractory multiple myeloma, with numerous novel agents and combination strategies receiving regulatory approval worldwide during the past several years. An increasing body of phase III data has clearly demonstrated increased overall response rates, improved depths of response, and more durable responses when a third novel agent is incorporated into lenalidomide-dexamethasone and bortezomib-dexamethasone platforms, in most cases with acceptable toxicity...
November 23, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27933373/outcomes-of-multiple-myeloma-patients-receiving-bortezomib-lenalidomide-and-carfilzomib
#14
Ariana Berenson, Suzie Vardanyan, Michael David, James Wang, Nika Manik Harutyunyan, Jillian Gottlieb, Ran Halleluyan, Tanya M Spektor, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, Benjamin Eades, Regina Swift, James R Berenson
New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited...
December 8, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27925676/population-pharmacokinetics-and-exposure-response-relationship-of-carfilzomib-in-patients-with-multiple-myeloma
#15
Ying Ou, Sameer Doshi, Anh Nguyen, Fredrik Jonsson, Sanjay Aggarwal, Kanya Rajangam, Meletios A Dimopoulos, A Keith Stewart, Ashraf Badros, Kyriakos P Papadopoulos, David Siegel, Sundar Jagannath, Ravi Vij, Ruben Niesvizky, Richard Graham, Jenn Visich
A population pharmacokinetic (PK) model and exposure-response (E-R) analysis was developed using data collected from 5 phase 1b/2 and 2 phase 3 studies in subjects with multiple myeloma. Subjects receiving intravenous infusion on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) in each cycle at doses ranging from 15 to 20/56 mg/m(2) (20 mg/m(2) in cycle 1 and, if tolerated, escalated to 56 mg/m(2) on day 8 of cycle 1). The population PK analysis indicated that among all the covariates tested, the only statistically significant covariate was body surface area on carfilzomib clearance; however, this covariate was unlikely to be clinically significant...
December 7, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#16
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#17
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#18
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27900802/therapeutic-potential-of-carfilzomib-an-irreversible-proteasome-inhibitor-against-acetaminophen-induced-hepatotoxicity-in-mice
#19
Abdulrazaq Alanazi, Saleh G Algfeley, Khaled A Al-Hosaini, Hesham M Korashy, Faisal Imam, Mahmoud N Nagi
Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti-inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP-induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis...
November 30, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#20
Marco Salvini, Francesca Bonello, Mario Boccadoro, Alessandra Larocca
In the last decade the introduction of novel agents has strongly improved multiple myeloma prognosis by doubling median overall survival. Unfortunately disease relapse is very common and patients may become refractory to previous drugs. Therefore, new therapeutic strategies are urgently needed. Areas covered: We have reviewed the available data on next generation novel agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors carfilzomib and ixazomib, the latter being the first-in-class orally available...
January 2017: Expert Review of Anticancer Therapy
keyword
keyword
46621
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"