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https://www.readbyqxmd.com/read/28081486/front-line-treatment-of-cll-in-the-era-of-novel-agents
#1
REVIEW
Tadeusz Robak, Stephan Stilgenbauer, Alessandra Tedeschi
Although chemoimmunotherapy prolongs survival and as such, is the standard of care for treatment-naïve patients, its effectiveness may be reduced by associated toxicity and dose reductions. In addition, it has been associated with the development of myelosuppression and secondary neoplasms; treatments are hence needed which offer greater survival and lowered toxicity. A range of new targeted agents, ibrutinib, idelalisib and venetoclax, have demonstrated such a balance in a second-line setting, offering CLL patients durable remissions and a modest toxicity profile...
December 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28076709/phase-3-trial-of-177-lu-dotatate-for-midgut-neuroendocrine-tumors
#2
RANDOMIZED CONTROLLED TRIAL
Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L Kunz, Matthew H Kulke, Heather Jacene, David Bushnell, Thomas M O'Dorisio, Richard P Baum, Harshad R Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro, Thomas Thevenet, Jack L Erion, Philippe Ruszniewski, Dik Kwekkeboom, Eric Krenning
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7...
12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28072602/-janus-kinase-ing-up-the-treatment-of-primary-myelofibrosis-building-better-combination-strategies
#3
Rita Assi, Srdan Verstovsek, Naval Daver
PURPOSE OF REVIEW: The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors-based combinatorial strategies in this setting. RECENT FINDINGS: Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of life, and an overall survival advantage with prolonged follow-up...
January 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28066120/eyelid-and-feet-edema-induced-by-pemetrexed
#4
Sarrah Kastalli, Ons Charfi, Rym Sahnoun, Ghozlane Lakhoua
Pemetrexed is an anti-metabolite that targets multiple enzymes in folate pathway. The main toxicities associated with pemetrexed are asthenia, nausea, diarrhea, myelosuppression, and rash. Few cases of pemetrexed induced cutaneous adverse event have been reported, mainly periorbital-facial edema and edema of the limbs. We report a case of pemetrexed-induced edema of the eyelid and feet in a patient with adenocarcinoma of the lung.
November 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28064553/granulocyte-colony-stimulating-factors-in-the-prevention-of-febrile-neutropenia-review-of-cost-effectiveness-models
#5
Kelly Fust, Anju Parthan, Michael Maschio, Qing Gu, Xiaoyan Li, Gary H Lyman, Spiros Tzivelekis, Guillermo Villa, Milton C Weinstein
We reviewed the evolution of the methods used in cost-effectiveness analyses of granulocyte colony-stimulating factors (G-CSFs) in the primary and secondary prevention of febrile neutropenia (FN) in patients receiving myelosuppressive cancer chemotherapy. Areas covered: FN is a side effect of myelosuppressive chemotherapy associated with significant morbidity, mortality, and costs. The risk of FN may depend on the drugs used within a chemotherapy regimen, and an FN event may cause chemotherapy dose reductions or delays in subsequent cycles...
January 9, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28057663/parp-inhibitor-and-chemotherapy-combination-trials-for-the-treatment-of-advanced-malignancies-does-a-development-pathway-forward-exist
#6
EDITORIAL
U A Matulonis, B J Monk
Poly (ADP ribose) polymerase (PARP) inhibitor combinations are currently being explored as a treatment strategy for advanced cancers with some or no known DNA repair deficits in order to increase the anti-cancer potential of both the PARP inhibitor and the chemotherapy partner. However, overlapping myelosuppression necessitating lowering of the PARP inhibitor and chemotherapy doses has unknown effects on efficacy. In addition, establishment of pre-clinical efficacy will be critical in moving these combinations rationally forward for further clinical development...
January 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28042456/safety-and-efficacy-of-azacitidine-in-elderly-patients-with-intermediate-to-high-risk-myelodysplastic-syndromes
#7
REVIEW
Shyamala C Navada, Lewis R Silverman
Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, a hyperproliferative bone marrow, and one or more peripheral blood cytopenias. In patients classified according to the Revised International Prognostic Scoring System (R-IPSS) with intermediate or higher-risk disease, there is an increased risk of death due to progressive bone marrow failure or transformation to acute myeloid leukemia (AML). Azacitidine was the first DNA hypomethylating agent approved by the United States (US) Food and Drug Administration (FDA) for the treatment of MDS and the only therapy that has demonstrated a significant survival benefit over conventional care regimens (CCRs) in patients with intermediate or higher-risk disease...
January 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28040066/effects-of-ambroxol-hydrochloride-on-concentrations-of-paclitaxel-and-carboplatin-in-lung-cancer-patients-at-different-administration-times
#8
J Li, W Yi, P Jiang, R Sun, T Li
Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration...
November 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28009503/coadministration-of-oligomeric-hyaluronic-acid-modified-liposomes-with-tumor-penetrating-peptide-irgd-enhances-the-antitumor-efficacy-of-doxorubicin-against-melanoma
#9
Caifeng Deng, Quan Zhang, Yao Fu, Xun Sun, Tao Gong, Zhirong Zhang
A safe and efficient tumor-targeting strategy based on oligomeric hyaluronic acid (HA) modification and coadministration of tumor-penetrating peptide-iRGD was successfully developed. In this study, common liposomes (cLip) were modified by oligomeric HA to obtain HA-Lip. After injection into rats, HA-Lip showed good stealth in the bloodstream and lower liver distribution compared with cLip. Moreover, our HA-Lip could be internalized into B16F10 cells (CD44-overexpressing tumor cells) through HA-CD44 interaction...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28000664/endothelial-specific-inhibition-of-nf-%C3%AE%C2%BAb-enhances-functional-haematopoiesis
#10
Michael G Poulos, Pradeep Ramalingam, Michael C Gutkin, Maria Kleppe, Michael Ginsberg, Michael J P Crowley, Olivier Elemento, Ross L Levine, Shahin Rafii, Jan Kitajewski, Matthew B Greenblatt, Jae-Hyuck Shim, Jason M Butler
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27998189/letermovir-for-the-management-of-cytomegalovirus-infection
#11
Lyndsey J Bowman, Jennifer Iuppa Melaragno, Daniel C Brennan
Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients. Available antivirals are fraught with adverse effects and risk for the development of CMV resistance. Letermovir is a novel antiviral in the late stages of drug development for the treatment and prevention of CMV. Areas covered: A MEDLINE search of the MeSH terms 'letermovir,' 'cytomegalovirus,' 'hematopoietic stem cell transplant,' and 'solid organ transplant,' was last conducted on 15 August 2016. Articles were selected on the basis of their contribution to current knowledge about letermovir...
December 28, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27994066/phase-iii-randomized-study-of-radiation-and-temozolomide-versus-radiation-and-nitrosourea-therapy-for-anaplastic-astrocytoma-results-of-nrg-oncology-rtog-9813
#12
Susan Chang, Peixin Zhang, J Gregory Cairncross, Mark R Gilbert, Jean-Paul Bahary, Carol A Dolinskas, Arnab Chakravarti, Kenneth D Aldape, Erica H Bell, David Schiff, Kurt Jaeckle, Paul D Brown, Geoffrey R Barger, Maria Werner-Wasik, Helen Shih, David Brachman, Marta Penas-Prado, H Ian Robins, Karl Belanger, Christopher Schultz, Grant Hunter, Minesh Mehta
BACKGROUND: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. METHODS: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99)...
December 18, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27986986/a-pharmacokinetic-study-of-lipegfilgrastim-in-children-with-ewing-family-of-tumors-or-rhabdomyosarcoma
#13
Margarita B Belogurova, Zoryana P Kizyma, Miklós Garami, Mónika Csóka, Michael J Lamson, Anton Buchner, Peter Bias, Andreas Lammerich
PURPOSE: Neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy...
December 16, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27956543/drug-development-pipeline-for-myeloproliferative-neoplasms-potential-future-impact-on-guidelines-and-management
#14
REVIEW
Prithviraj Bose, Srdan Verstovsek
The unprecedented success of ruxolitinib in myelofibrosis (MF) has paved the way for the development of other Janus kinase (JAK) inhibitors and other agents representing diverse drug classes and mechanisms of action in myeloproliferative neoplasms (MPNs). In particular, the symptomatic benefits afforded by ruxolitinib have led to the recognition of "clinical improvement" in symptoms and the spleen in international consensus response criteria for MF. Ruxolitinib is also approved for the second-line treatment of polycythemia vera and is being developed for essential thrombocythemia...
December 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27951730/long-non-coding-rna-gas5-polymorphism-predicts-a-poor-prognosis-of-acute-myeloid-leukemia-in-chinese-patients-via-affecting-hematopoietic-reconstitution
#15
Han Yan, Dao-Yu Zhang, Xi Li, Xiao-Qing Yuan, Yong-Long Yang, Ke-Wei Zhu, Hui Zeng, Xiao-Lin Li, Shan Cao, Hong-Hao Zhou, Wei Zhang, Xiao-Ping Chen
Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T > C) was significantly associated with prognosis of AML (p = 0.018). Patients with rs55829688 CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p = 0...
December 12, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27941424/characterization-of-neurologic-and-ophthalmologic-safety-of-oral-administration-of-tedizolid-for-up-to-21-days-in-healthy-volunteers
#16
Edward Fang, Kelly A Muñoz, Philippe Prokocimer
BACKGROUND: Antibacterials that inhibit protein synthesis may be associated with mitochondrial toxicity, manifested as serious optic or peripheral neuropathy or myelosuppression. Tedizolid is a novel oxazolidinone antibacterial that may have reduced the potential for mitochondrial toxicity. STUDY QUESTION: Based on the results of 2 studies (NCT01623401 and NCT00671814) conducted early in the tedizolid development program, what is the potential for drug-induced optic and peripheral neuropathies with tedizolid treatment? METHODS: Two phase-1 studies were conducted in healthy volunteers...
November 15, 2016: American Journal of Therapeutics
https://www.readbyqxmd.com/read/27939823/the-combined-effect-of-resveratrol-and-diphenyleneiodonium-on-irradiation-induced-injury-to-the-hematopoietic-system
#17
Junling Zhang, Xiaodan Han, Song Huang, Lu Lu, Deguan Li, Aimin Meng
Both resveratrol(Res) and diphenyleneiodonium(DPI) have been shown to have radioprotective effects on hematopoietic system injury. However, the cooperative effect of Res and DPI are unknown. In this study, we explored the radioprotective effect of the combination of Res and DPI both in vitro and in vivo. Our results showed that the combined treatment of Res and DPI was more effective in protecting irradiated BMMNCs in terms of cell viability, colony-forming ability, and reconstitution ability in vitro compared with Res or DPI treatment alone...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27931810/evaluation-of-in-vivo-gene-mutation-with-etoposide-using-pig-a-and-pigret-assays
#18
Mika Yamamoto, Akihiro Wakata
The Pig-a assay detects the expression of the endogenous phosphatidylinositol glycan anchor biosynthesis, class A gene (Pig-a) as a reporter of mutations and shows promise for detecting mutations in vivo. This assay requires two to four weeks to detect mutations in erythrocytes after animals are administered a single dose of test compound. In contrast, the more recently developed PIGRET assay using reticulocytes detects mutation sensitively one week after dosing, which is an advantage for conducting short-term genotoxicity studies in vivo...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27931243/phase-1-2-study-of-pacritinib-a-next-generation-jak2-flt3-inhibitor-in-myelofibrosis-or-other-myeloid-malignancies
#19
Srdan Verstovsek, Olatoyosi Odenike, Jack W Singer, Tanya Granston, Suliman Al-Fayoumi, H Joachim Deeg
BACKGROUND: Pacritinib (SB1518) is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD), safety, and clinical activity of pacritinib in patients with myelofibrosis (MF) and other advanced myeloid malignancies. METHODS: In the phase 1 dose-escalation part of the study, 43 adults with advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD)...
December 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27923827/preclinical-evidence-that-3-deoxy-3-18f-fluorothymidine-pet-can-visualize-recovery-of-hematopoiesis-after-gemcitabine-chemotherapy
#20
Sonja Schelhaas, Annelena Held, Nicole Bäumer, Thomas Viel, Sven Hermann, Carsten Müller-Tidow, Andreas H Jacobs
Molecular imaging with the PET tracer 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) allows assessment of the proliferative state of organs in vivo Although used primarily in the oncology clinic, it can also shed light on the proliferation of other tissues, as demonstrated here for monitoring hematopoietic organs that recover after myelosuppressive chemotherapy. In the NMRI nude mouse model, we observed up to a 4.5-fold increase in [(18)F]FLT uptake in bone marrow and spleen on days 2, 3, and 5 after treatment with gemcitabine, a chemotherapeutic agent that is powerfully myelosuppressive in the model...
December 15, 2016: Cancer Research
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