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https://www.readbyqxmd.com/read/28726132/phase-i-dose-escalation-study-of-nms-1286937-an-orally-available-polo-like-kinase-1-inhibitor-in-patients-with-advanced-or-metastatic-solid-tumors
#1
Glen J Weiss, Gayle Jameson, Daniel D Von Hoff, Barbara Valsasina, Cristina Davite, Claudia Di Giulio, Francesco Fiorentini, Rachele Alzani, Patrizia Carpinelli, Alessandro Di Sanzo, Arturo Galvani, Antonella Isacchi, Ramesh K Ramanathan
Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue...
July 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28726066/palliative-care-needs-in-hospitalized-cancer-patients-a-5-year-follow-up-study
#2
A Sandgren, P Strang
PURPOSE: The aims of this study were to describe and compare diagnoses, symptoms, and care needs in palliative cancer patients in two medium-sized hospitals in a county council with no specialized palliative care available 24/7; to analyze the relationships between diagnosis and symptoms/care needs; and to compare results and trends from two datasets (from 2007 and 2012). METHODS: The study was population-based with a cross-sectional design and was conducted at two acute care hospitals...
July 19, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28725989/imatinib-in-myeloid-lymphoid-neoplasms-with-eosinophilia-and-rearrangement-of-pdgfrb-in-chronic-or-blast-phase
#3
Mohamad Jawhar, Nicole Naumann, Juliana Schwaab, Herrad Baurmann, Jochen Casper, Tu-Anh Dang, Lutz Dietze, Konstanze Döhner, Annette Hänel, Bernd Lathan, Hartmut Link, Sina Lotfi, Ole Maywald, Stephan Mielke, Lothar Müller, Uwe Platzbecker, Otto Prümmer, Henrike Thomssen, Karin Töpelt, Jens Panse, Tom Vieler, Wolf-Karsten Hofmann, Torsten Haferlach, Claudia Haferlach, Alice Fabarius, Andreas Hochhaus, Nicholas C P Cross, Andreas Reiter, Georgia Metzgeroth
We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10(9)/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively...
July 19, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28709705/phase-ii-trial-of-neoadjuvant-chemotherapy-followed-by-chemoradiation-in-locally-advanced-cervical-cancer
#4
Carla Rameri Alexandre Silva de Azevedo, Luiz Cláudio Santos Thuler, Maria Júlia Gonçalves de Mello, Jurema Telles de Oliveira Lima, Ana Luiza Fassizoli da Fonte, Diógenes Fernando Santos Fontão, Vandré Cabral Gomes Carneiro, Tien Man Cabral Chang, Carlos Gil Ferreira
OBJECTIVE: Cervical cancer is a global public health challenge. Since 1999, platin based chemoradiation (CRT) is the standard treatment for those patients with locally advanced disease. However, this population still has a dismal prognosis and, alternatives approaches such as adjuvant chemotherapy are controversial, especially because of increased toxicity. Neoadjuvant chemotherapy (NACT) could be an option for more intensive treatment with manageable toxicity. METHODS: A phase II, prospective, non-randomized trial was conducted at a reference center in Recife, Brazil...
July 11, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28708230/short-course-radiotherapy-concomitant-with-temozolomide-in-gbm-patients-a-phase-ii-study
#5
Laura Fariselli, Lucia Cuppini, Paola Gaviani, Marcello Marchetti, Valentina Pinzi, Ida Milanesi, Giorgia Simonetti, Irene Tramacere, Francesco DiMeco, Andrea Salmaggi, Antonio Silvani
PURPOSE: Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. METHODS: This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity...
July 8, 2017: Tumori
https://www.readbyqxmd.com/read/28705540/three-year-safety-of-radium-223-dichloride-in-patients-with-castration-resistant-prostate-cancer-and-symptomatic-bone-metastases-from-phase-3-randomized-alpharadin-in-symptomatic-prostate-cancer-trial
#6
Christopher C Parker, Robert E Coleman, Oliver Sartor, Nicholas J Vogelzang, David Bottomley, Daniel Heinrich, Svein I Helle, Joe M O'Sullivan, Sophie D Fosså, Aleš Chodacki, Paweł Wiechno, John Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Peter Hoskin, Nicholas D James, Arne Solberg, Isabel Syndikus, Jan Kliment, Steffen Wedel, Sibylle Boehmer, Marcos Dall'Oglio, Lars Franzén, Øyvind S Bruland, Oana Petrenciuc, Karin Staudacher, Rui Li, Sten Nilsson
BACKGROUND: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. OBJECTIVE: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. DESIGN, SETTING, AND PARTICIPANTS: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving ≥1 study-drug injection (600 radium-223 and 301 placebo)...
July 10, 2017: European Urology
https://www.readbyqxmd.com/read/28704757/structural-optimization-elaborates-novel-potent-akt-inhibitors-with-promising-anticancer-activity
#7
Yang Liu, Yanzhen Yin, Zhen Zhang, Carrie J Li, Hui Zhang, Daoguang Zhang, Changying Jiang, Krystle Nomie, Liang Zhang, Michael L Wang, Guisen Zhao
Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Akt1. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells...
June 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28702409/phase-iib-trial-comparing-two-concurrent-cisplatin-schedules-in-locally-advanced-head-and-neck-cancer
#8
Lekha Madhavan Nair, R Rejnish Kumar, Kainickal Cessal Thomachan, Malu Rafi, Preethi Sara George, K M Jagathnath Krishna, Kunnambath Ramadas
BACKGROUND: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m(2)) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. OBJECTIVES: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m(2)) with weekly cisplatin (40 mg/m(2)) concurrently with radiation in patients with locally advanced head and neck cancer...
April 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28696817/reference-database-of-hematological-parameters-for-growing-and-aging-rats
#9
Wilson Jacob Filho, Caio Cezar Lima, Marcos Rodolfo Ramos Paunksnis, Ariana Aline Silva, Mauro Sérgio Perilhão, Marina Caldeira, Danilo Bocalini, Romeu Rodrigues de Souza
The normal hematological values in various phases of the rat life provide a valuable guide to researchers and could be useful for experimental works. However, database information available on the literature are incomplete. AIM: This study aimed to present normal hematological parameters of young and aged rats. METHODS: Male and female rats were distributed into seven experimental groups with 1, 2, 3, 6, 12, 18, and 24 months of age. Blood samples taken from the tails were analyzed...
July 11, 2017: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/28696812/a-phase-i-trial-of-bortezomib-in-combination-with-everolimus-for-treatment-of-relapsed-refractory-non-hodgkin-lymphoma
#10
Brian T Hill, Mitchell R Smith, Meredeth Shelley, Deepa Jagadeesh, Robert M Dean, Brad Pohlman, John W Sweetenham, Brian J Bolwell, Stephen D Smith
B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1...
July 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28693283/prospective-exploratory-study-of-gemcitabine-and-s-1-against-elderly-patients-with-advanced-non-small-cell-lung-cancer
#11
Kyoichi Kaira, Noriko Yanagitani, Noriaki Sunaga, Hisao Imai, Akihiro Ono, Yasuhiko Koga, Takeshi Hisada, Tamotsu Ishizuka, Masanobu Yamada
A prospective study was conducted to investigate the efficacy of a combined regimen of gemcitabine and S-1 for the treatment of elderly patients (>70 years) with advanced non-small cell lung cancer (NSCLC) as a first-line setting based on the dosage recommended in a previous phase I study. Chemotherapy-naïve patients with advanced NSCLC received gemcitabine plus S-1. S-1 (40 mg/m(2)) was administered orally twice daily for 14 days while gemcitabine (1,000 mg/m(2)) was administered on days 1 and 15 of each cycle, and this regimen was repeated every 4 weeks...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28688052/carboplatin-plus-weekly-nanoparticle-albumin-bound-paclitaxel-in-elderly-patients-with-previously-untreated-advanced-squamous-non-small-cell-lung-cancer-selected-based-on-mini-nutritional-assessment-short-form-scores-a-multicenter-phase-2-study
#12
Takayuki Shiroyama, Motohiro Tamiya, Seigo Minami, So Takata, Kentaro Masuhiro, Yu Futami-Nishijima, Takeshi Uenami, Masahide Mori, Taro Koba, Takanori Matsuki, Takayuki Takimoto, Hidekazu Suzuki, Norio Okamoto, Kiyoshi Komuta, Tomonori Hirashima, Atsushi Kumanogoh, Takashi Kijima
PURPOSE: This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF). METHODS: Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m(2)) on Days 1, 8, and 15, every 28 days for ≤4 cycles...
July 7, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28678741/role-of-nab-paclitaxel-in-metastatic-breast-cancer-a-meta-analysis-of-randomized-clinical-trials
#13
Yun Liu, Guoxin Ye, Dali Yan, Lei Zhang, Fan Fan, Jifeng Feng
Whether nab-paclitaxel and conventional taxanes are equally effective for metastatic breast cancer (MBC) remains unclear. We conducted meta-analysis of trials that compared nab-paclitaxel-based chemotherapy with solvent-based paclitaxel (sb-paclitaxel) and docetaxel-based chemotherapy. A literature search was performed to identify articles that compared nab-paclitaxel-based chemotherapy with sb-paclitaxel or docetaxel-based chemotherapy for MBC. Four randomized controlled trials (1,506 patients) were identified from 1,268 reports...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28669446/inflammation-and-myeloproliferative-neoplasms
#14
REVIEW
Federico Lussana, Alessandro Rambaldi
Myeloproliferative neoplasms (MPN) include three main entities: Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis (MF). MPN represent a unique model of the relationship between the clonal development of a hematologic malignancy and chronic inflammation. The neoplastic clone is the main driver of this inflammatory reaction as demonstrated by the curative effect of allogeneic stem cell transplantation which leads not only to a complete restore of the hematopoiesis, but also to regression of bone marrow fibrosis...
June 29, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28669167/the-prognostic-value-of-pre-treatment-leukocytosis-in-patients-with-previously-treated-stage-iiib-iv-non-small-cell-lung-cancer-treated-with-the-igf-1r-pathway-modulator-axl1717-or-docetaxel-a-retrospective-analysis-of-a-phase-ii-trial
#15
Georg Holgersson, Michael Bergqvist, Jonas Nilsson, Marcus Thureson, Johan Harmenberg, Stefan Bergstrom
Background: The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC. Methods: A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28669012/report-of-safety-of-pulse-dosing-of-lapatinib-with-temozolomide-and-radiation-therapy-for-newly-diagnosed-glioblastoma-in-a-pilot-phase-ii-study
#16
Andrew Yu, Nadia Faiq, Stacey Green, Albert Lai, Richard Green, Jethro Hu, Timothy F Cloughesy, Ingo Mellinghoff, P Leia Nghiemphu
Epidermal growth factor receptor (EGFR) mutations are commonly observed in Glioblastoma (GBM) and have long posed as a target for new therapies. Trials involving erlotinib have shown mixed results, likely owing to a mechanism of the mutation that may instead favor other EGFR inhibitors, such as lapatinib. We aimed to determine whether or not pulse high-dose lapatinib was a safe and tolerable regimen in addition to standard therapy. We recruited adult patients with newly-diagnosed GBM who had Karnofsky Performance Status ≥60, normal baseline hematological, hepatic, and renal function tests, and no prior history of radiation or treatment with EGFR inhibitor...
July 1, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28662033/a-phase-i-study-of-pazopanib-in-combination-with-escalating-doses-of-131i-in-patients-with-well-differentiated-thyroid-carcinoma-borderline-refractory-to-radioiodine
#17
Laura Q Chow, Rafael Santana-Davila, Austin Pantel, Mara Roth, Leslie N Anderson, Alan Failor, Robert Doot, David Mankoff
OBJECTIVE: This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131I resistance. MATERIALS, METHODS AND PATIENTS: This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans. Patients underwent FDG PET/CT before and after the initial pazopanib treatment to identify the impact of pazopanib on the cancer prior to 131I therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28656383/a-phase-ii-study-of-irinotecan-and-pegylated-liposomal-doxorubicin-in-platinum-resistant-recurrent-ovarian-cancer-tohoku-gynecologic-cancer-unit-104-study
#18
Tadahiro Shoji, Eriko Takatori, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Masayuki Futagami, Yoshihito Yokoyama, Michiko Kaiho, Hideki Tokunaga, Takeo Otsuki, Tadao Takano, Nobuo Yaegashi, Takanobu Kojimahara, Tsuyoshi Ohta, Satoru Nagase, Shu Soeda, Takafumi Watanebe, Hiroshi Nishiyama, Toru Sugiyama
PURPOSE: We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial. METHODS: PLD was administered intravenously at a dose of 30 mg/m(2) on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m(2) on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression...
June 27, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28651194/reference-intervals-for-hematological-and-biochemical-parameters-acute-phase-proteins-and-markers-of-oxidation-in-holstein-dairy-cows-around-3-and-30days-after-calving
#19
Pierangelo Moretti, Saverio Paltrinieri, Erminio Trevisi, Monica Probo, Annarita Ferrari, Andrea Minuti, Alessia Giordano
The establishment of specific reference intervals (RIs) is advisable when different metabolic conditions in the patient population are present or when existing RIs are not suitable. Holstein dairy cows, at the start of lactation, experience a negative energy balance and an altered immune function that can lead to different levels of blood parameters compared with cows at peak lactation. The aim of this study was the determination of RIs for Holstein cows at 3±1 and 30±3days in milk. To this aim, 145 cows, from 4 herds, were sampled...
June 20, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28646676/multicenter-phase-2-study-of-combination-therapy-with-ruxolitinib-and-danazol-in-patients-with-myelofibrosis
#20
K Gowin, H Kosiorek, A Dueck, J Mascarenhas, R Hoffman, C Reeder, J Camoriano, R Tibes, K Gano, J Palmer, R Mesa
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol...
June 13, 2017: Leukemia Research
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