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myelosuppression

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https://www.readbyqxmd.com/read/29338080/phase-1-trial-evaluating-cisplatin-gemcitabine-and-veliparib-in-2-patient-cohorts-germline-brca-mutation-carriers-and-wild-type-brca-pancreatic-ductal-adenocarcinoma
#1
Eileen M O'Reilly, Jonathan W Lee, Maeve A Lowery, Marinela Capanu, Zsofia K Stadler, Malcolm J Moore, Neesha Dhani, Hedy L Kindler, Hayley Estrella, Hannah Maynard, Talia Golan, Amiel Segal, Erin E Salo-Mullen, Kenneth H Yu, Andrew S Epstein, Michal Segal, Robin Brenner, Richard K Do, Alice P Chen, Laura H Tang, David P Kelsen
BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29328910/modulation-of-myelopoiesis-progenitors-is-an-integral-component-of-trained-immunity
#2
Ioannis Mitroulis, Klara Ruppova, Baomei Wang, Lan-Sun Chen, Michal Grzybek, Tatyana Grinenko, Anne Eugster, Maria Troullinaki, Alessandra Palladini, Ioannis Kourtzelis, Antonios Chatzigeorgiou, Andreas Schlitzer, Marc Beyer, Leo A B Joosten, Berend Isermann, Mathias Lesche, Andreas Petzold, Kai Simons, Ian Henry, Andreas Dahl, Joachim L Schultze, Ben Wielockx, Nicola Zamboni, Peter Mirtschink, Ünal Coskun, George Hajishengallis, Mihai G Netea, Triantafyllos Chavakis
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29321348/influence-of-thiopurine-methyltransferase-gene-polymorphism-on-egyptian-children-with-acute-lymphoblastic-leukaemia
#3
Azza A G Tantawy, Fatma S E Ebeid, Amira A M Adly, Eman El-Ghoroury, Mai Mostafa
Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29317553/safety-profile-of-biosimilar-filgrastim-zarzio-zarxio-a-combined-analysis-of-phase-iii-studies
#4
Nadia Harbeck, Pere Gascón, Andriy Krendyukov, Nadja Hoebel, Sreekanth Gattu, Kimberly Blackwell
BACKGROUND: Evaluation of adverse events (AEs) in pivotal registration trials and ongoing postmarketing surveillance is important for all biologics, including biosimilars. A combined analysis of two pivotal registration studies was performed to strengthen evidence on safety for biosimilar filgrastim EP2006 in patients with breast cancer receiving myelosuppressive chemotherapy, a sensitive clinical setting to confirm biosimilarity of filgrastim. MATERIALS AND METHODS: Data were combined from two phase III studies of biosimilar filgrastim EP2006...
January 9, 2018: Oncologist
https://www.readbyqxmd.com/read/29316372/can-therapeutic-drug-monitoring-increase-the-safety-of-imatinib-in-gist-patients
#5
Wei Zhuang, Jing-Dun Xie, Shan Zhou, Zhi-Wei Zhou, Yi Zhou, Xiao-Wei Sun, Xiu-Hong Yuan, Min Huang, Si Liu, Shuang Xin, Qi-Biao Su, Hai-Bo Qiu, Xue-Ding Wang
Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin ) with adverse effects (AEs) was described here...
January 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29311252/pazopanib-induced-hypertension-in-patients-with-renal-cell-carcinoma-is-associated-with-low-urine-excretion-of-no-metabolites
#6
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29305999/high-fat-diet-induced-obesityexacerbateshematopoiesis-deficiency-and-cytopenia-caused-by-5-fluorouracil-via-ppar-%C3%AE
#7
Yanhong Li, Shuai Zhu, Yuanyuan Zhang, Ting Liu, Linchong Su, Qiuping Zhang, Yubin Luo
The present study aims to investigate the influence of high fat diet (HFD) on hematopoietic system recovery under stress condition caused by 5-Fluouracil (5-Fu) and evaluate the alleviating benefit of PPAR-γ inhibition on aggravation of 5-Fu-induced toxicity under HFD condition. Survival rate of HFD or normal diet (ND) mice was monitored after 5-Fu injection. HSC and the progenitor cells in bone marrow were detected at various time points after 5-Fu administration by flow cytometry. Genes expression involved in stem cell and platelet proliferation were tested by RT-PCR...
January 3, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29299638/prediction-of-neutrophil-reduction-using-plasma-paclitaxel-concentration-after-administration-in-patients-with-uterine-ovarian-or-cervical-cancers-in-an-outpatient-clinic
#8
Motoaki Ishikawa, Michiyasu Kawai, Toshio Maeda, Yoshiyuki Kagawa
PURPOSE: Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic. METHODS: Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration...
January 3, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29296753/an-aptamer-based-targeted-delivery-of-mir-26a-protects-mice-against-chemotherapy-toxicity-while-suppressing-tumor-growth
#9
Toshihiko Tanno, Peng Zhang, Christopher A Lazarski, Yang Liu, Pan Zheng
The efficacy of traditional chemotherapy is limited by its toxicity, especially with regard to hematopoiesis. Here we show that miR-26a plays a critical role in protecting mice against chemotherapy-induced myeloid suppression by targeting a proapoptotic protein (Bak1) in hematopoietic stem/progenitor cells (HSPCs). Because c-Kit is expressed at high levels in HSPCs, we designed a microRNA-aptamer chimera that contains miR-26a mimic and c-Kit-targeting aptamer and successfully delivered miR-26a into HSPCs to attenuate toxicity of 5' fluorouracil (5-FU) and carboplatin...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285384/the-combination-of-paclitaxel-and-carboplatin-as-second-line-chemotherapy-can-be-a-preferred-regimen-for-patients-with-urothelial-carcinoma-after-the-failure-of-gemcitabine-and-cisplatin-chemotherapy
#10
Nobuki Furubayashi, Takahito Negishi, Takuya Yamashita, Shuhei Kusano, Kenichi Taguchi, Mototsugu Shimokawa, Motonobu Nakamura
There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29275079/efficacy-and-safety-of-iodine-125-radioactive-seeds-brachytherapy-for-advanced-non-small-cell-lung-cancer-a-meta-analysis
#11
REVIEW
Wenchao Zhang, Jiawei Li, Ran Li, Ying Zhang, Mingyong Han, Wei Ma
PURPOSE: This meta-analysis was conducted to investigate the efficacy and safety of 125I brachytherapy for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Trials comparing 125I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS). RESULTS: Fifteen studies including 1188 cases were included...
December 20, 2017: Brachytherapy
https://www.readbyqxmd.com/read/29260599/alisertib-a-review-of-pharmacokinetics-efficacy-and-toxicity-in-patients-with-hematologic-malignancies-and-solid-tumors
#12
Susanne Liewer, Ashley Huddleston
Aurora kinases are essential mediators in cell mitosis. Amplification of these kinases can lead to the development of malignancy and may be associated with inferior survival. Alisertib is an oral aurora kinase inhibitor which has been shown to induce cell-cycle arrest and apoptosis in preclinical studies. It is currently under investigation for a wide variety of malignancies including hematologic (specifically Non-Hodgkin's lymphoma) and solid tumors. Areas covered: A PubMed search was performed to identify clinical studies reporting outcomes with alisertib...
December 20, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29259833/small-split-doses-of-cd34-peripheral-blood-stem-cells-to-support-repeated-cycles-of-nonmyeloablative-chemotherapy
#13
Maxim Yankelevich, Sureyya Savasan, Igor Dolgopolov, Roland Chu, George Mentkevich
Cumulative myelosuppression is the main limiting factor for administration of repeated cycles of chemotherapy. We present a case series of five pediatric patients with high-risk solid malignancies who received small split peripheral blood stem cells (PBSC) doses of less than 1 × 106/kg CD34+ cells obtained after a single leukapheresis procedure and given after repeated cycles of ICE (ifosfamide, carboplatin, and etoposide) chemotherapy. Mean duration to absolute neutrophil count (ANC) recovery to >1000/mm3 and platelet recovery to >50 × 103/mm3 was 17...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29245310/a-pilot-clinical-study-of-apatinib-plus-irinotecan-in-patients-with-recurrent-high-grade-glioma-clinical-trial-experimental-study
#14
Lei Wang, Lijun Liang, Tao Yang, Yun Qiao, Youyou Xia, Liang Liu, Chao Li, Peizhi Lu, Xiaodong Jiang
BACKGROUND: Malignant glioma is the most common primary malignant brain tumor that displays high vascularity, making vascular endothelial growth factor receptors become promising targets. This study was conducted to evaluate the efficacy and safety of apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeted vascular endothelial growth factor receptor 2, combined with irinotecan, in patients with recurrent malignant glioma. METHODS: Ten patients with recurrent malignant glioma who were experiencing relapse after treatment of temozolomide were enrolled in this study...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29238995/test-dose-pharmacokinetics-in-pediatric-patients-receiving-once-daily-iv-busulfan-conditioning-for-hematopoietic-stem-cell-transplant-a-reliable-approach
#15
Kristina M Brooks, Paul Jarosinski, Thomas Hughes, Elizabeth Kang, Nirali N Shah, John B Le Gall, Dennis D Hickstein, Suk See De Ravin, Jomy M George, Parag Kumar
Intravenous (IV) busulfan test dose pharmacokinetics (PK) has been shown to accurately predict once-daily dose requirements and improve outcomes in adult transplant patients, but there are limited data to support this approach in children. Test doses of busulfan ∼0.8 mg/kg were infused over 2 to 3 hours, followed by serial sampling to 4-6 hours postinfusion in pediatric hematopoietic stem cell transplant recipients (n = 5). Once-daily busulfan doses were calculated based on a myelosuppressive area under the concentration-time curve (AUC) target of ∼3700 to 4000 μmol·min/L and assumed dose-proportionality to the test dose...
December 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29236223/transit-and-lifespan-in-neutrophil-production-implications-for-drug-intervention
#16
Daniel Câmara De Souza, Morgan Craig, Tyler Cassidy, Jun Li, Fahima Nekka, Jacques Bélair, Antony R Humphries
A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells...
December 13, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29235894/pacritinib-and-its-use-in-the-treatment-of-patients-with-myelofibrosis-who-have-thrombocytopenia
#17
Adolfo Enrique Diaz, Ruben A Mesa
The treatment landscape for myelofibrosis (MF) has reached the molecular era by targeting different pathways that are implied in this myeloproliferative neoplasm. A few years ago, the first-in-class JAK1/JAK2 inhibitor ruxolitinib, demonstrated reductions in both constitutional symptoms and splenomegaly, leading to the US FDA approval. The development or worsening of cytopenias in patients receiving ruxolitinib uncovered an unmet need that has been addressed by alternative approaches. Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity...
December 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29233162/sarcomatoid-hepatocellular-carcinoma-shc-a-case-report
#18
Yingying Yu, Yanping Zhong, Jingyu Wang, Di Wu
BACKGROUND: Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant hepatic tumor. Recurrent interventional therapies such as transcatheter arterial chemo-embolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection have been reported previously utilized in a majority of SHC cases. To date, the exact pathogenic mechanisms underlying sarcomatoid transformation of hepatocellular carcinoma (HCC) remain unknown. CASE PRESENTATION: In this study, we report a 68-year-old female SHC patient admitted to our hospital due to discrete abdominal distention for more than 20 days...
December 12, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29232318/significant-effect-of-acupressure-in-elevating-blood-stem-cell-factor-during-chemotherapy-in-patients-with-gynecologic-cancer
#19
Ya-Wen Shih, Shun-Fa Yang, Ming-Hsien Chien, Ching-Wen Chang, Vincent H S Chang, Hsiu-Ting Tsai
BACKGROUND: Chemotherapy is used mainly to treat and control the progression of gynecological cancer. Bone marrow suppression, one of the adverse side effects of chemotherapy, may decrease immune function, increasing the risk of serious, fatal infections. PURPOSE: The aims of this study were to evaluate the effectiveness of noninvasive acupressure in preventing and diminishing chemotherapy-induced myelosuppression in patients with gynecologic cancer and to determine whether this effect is associated with the regulation of the expressions of granulocyte-macrophage colony-stimulating factor and stem cell factor (SCF)...
December 9, 2017: Journal of Nursing Research: JNR
https://www.readbyqxmd.com/read/29230663/advantages-with-prophylactic-peg-rhg-csf-versus-rhg-csf-in-breast-cancer-patients-receiving-multiple-cycles-of-myelosuppressive-chemotherapy-an-open-label-randomized-multicenter-phase-iii-study
#20
Jie Xie, Jun Cao, Jing-Fen Wang, Bai-Hong Zhang, Xiao-Hua Zeng, Hong Zheng, Yang Zhang, Li Cai, Yu-Dong Wu, Qiang Yao, Xiao-Chun Zhao, Wei-Dong Mao, Ai-Mei Jiang, Shao-Shui Chen, Shun-E Yang, Shu-Sen Wang, Jian-Hong Wang, Yue-Yin Pan, Bi-Yong Ren, Yan-Ju Chen, Li-Zhi Ouyang, Kai-Jian Lei, Jing-Hua Gao, Wen-He Huang, Zhan Huang, Tao Shou, Yan-Ling He, Jing Cheng, Yang Sun, Wei-Ming Li, Shu-de Cui, Xin Wang, Zhi-Guo Rao, Hu Ma, Wei Liu, Xue-Yong Wu, Wei-Xi Shen, Fei-Lin Cao, Ze-Min Xiao, Biao Wu, Shu-Yan Tian, Dong Meng, Peng Shen, Bi-Yun Wang, Zhonghua Wang, Jian Zhang, Leiping Wang, Xi-Chun Hu
BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy...
December 11, 2017: Breast Cancer Research and Treatment
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