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https://www.readbyqxmd.com/read/28344046/long-term-outcomes-of-induction-carboplatin-and-gemcitabine-followed-by-concurrent-radiotherapy-with-low-dose-paclitaxel-and-gemcitabine-for-stage-iii-non-small-cell-lung%C3%A2-cancer
#1
Catherine Guilbault, Aurelie Garant, Sergio Faria, Scott Owen, Linda Ofiara, Marie Duclos, Vera Hirsh, Neil Kopek
BACKGROUND: Standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and nonprotocol patients. METHODS AND MATERIALS: Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28338993/dihydrocelastrol-inhibits-multiple-myeloma-cell-proliferation-and-promotes-apoptosis-through-erk1-2-and-il-6-stat3-pathways-in-vitro-and-in-vivo
#2
Liangning Hu, Huiqun Wu, Bo Li, Dongliang Song, Guang Yang, Gege Chen, Bingqian Xie, Zhijian Xu, Yong Zhang, Dandan Yu, Jun Hou, Wenqin Xiao, Xi Sun, Gaomei Chang, Yiwen Zhang, Lu Gao, Bojie Dai, Yi Tao, Jumei Shi, Weiliang Zhu
Multiple myeloma (MM) is the second most frequent malignant hematological disease. Dihydrocelastrol (DHCE) is synthesized by hydrogenated celastrol, a treterpene isolated from Chinese medicinal plant Tripterygium regelii. In this study, we first reported the anti-tumor activity of DHCE on MM cells. We found that DHCE could inhibit cell proliferation and promote apoptosis through caspase-dependent way in vitro. In addition, DHCE could inactivate the expression of interleukin (IL)-6 and downregulate the phosphorylation of extracellular regulated protein kinases (ERK1/2) and the signal transducer and activator of transcription 3 (STAT3) in MM...
March 17, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28337660/topgear-a-randomized-phase-iii-trial-of-perioperative-ecf-chemotherapy-with-or-without-preoperative-chemoradiation-for-resectable-gastric-cancer-interim-results-from-an-international-intergroup-trial-of-the-agitg-trog-eortc-and-cctg
#3
Trevor Leong, B Mark Smithers, Karin Haustermans, Michael Michael, Val Gebski, Danielle Miller, John Zalcberg, Alex Boussioutas, Michael Findlay, Rachel L O'Connell, Jaclyn Verghis, David Willis, Tomas Kron, Melissa Crain, William K Murray, Florian Lordick, Carol Swallow, Gail Darling, John Simes, Rebecca Wong
BACKGROUND: Postoperative chemoradiation and perioperative chemotherapy using epirubicin/cisplatin/5-fluorouracil (ECF) represent two standards of care for resectable gastric cancer. In the TOPGEAR (Trial Of Preoperative therapy for Gastric and Esophagogastric junction AdenocaRcinoma) trial, we hypothesized that adding preoperative chemoradiation to perioperative ECF will improve survival; however, the safety and feasibility of preoperative chemoradiation have yet to be determined. METHODS: TOPGEAR is an international phase III trial in which patients with adenocarcinoma of the stomach were randomized to perioperative ECF alone or with preoperative chemoradiation...
March 23, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28337527/phase-ii-study-of-the-c-met-inhibitor-tivantinib-arq-197-in-patients-with-relapsed-or-relapsed-refractory-multiple-myeloma
#4
Muhamed Baljevic, Shadia Zaman, Veerabhadran Baladandayuthapani, Yan Heather Lin, Claudia Morales de Partovi, Zuzana Berkova, Behrang Amini, Sheeba K Thomas, Jatin J Shah, Donna M Weber, Min Fu, Charles S Cleeland, Xin Shelley Wang, Christine M Stellrecht, Richard E Davis, Varsha Gandhi, Robert Z Orlowski
The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression...
March 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28336527/a-phase-i-clinical-trial-of-single-agent-selinexor-in-acute-myeloid-leukemia
#5
Ramiro Garzon, Michael Savona, Rachid Baz, Michael Andreeff, Nashat Gabrail, Martin Gutierrez, Lynn Savoie, Morten Mau-Sorensen, Nina Wagner-Johnston, Karen Yee, T J Unger, Jean Richard Saint-Martin, Robert Carlson, Tami Rashal, Trinayan Kashyap, Boris Klebanov, Sharon Shacham, Michael Kauffman, Richard Stone
Selinexor is a novel, first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, which blocks XPO1 function, leads to nuclear accumulation of tumor suppressor proteins (TSPs) and induces cancer cell death. A phase I dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8 or 10 doses of selinexor in 21- or 28-day cycle...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28334948/a-phase-i-ii-trial-of-continuous-hepatic-intra-arterial-infusion-of-5-fluorouracil-mitoxantrone-and-cisplatin-for-advanced-hepatocellular-carcinoma
#6
Masafumi Ikeda, Takuji Okusaka, Yozo Sato, Junji Furuse, Shuichi Mitsunaga, Hideki Ueno, Chigusa Morizane, Yoshitaka Inaba, Tatsushi Kobayashi, Yasuaki Arai
Background: The aim of this study was to investigate the dose-limiting toxicities (DLTs) and determine the recommended doses in the Phase I part of the study, and to evaluate the efficacy and toxicity in the Phase II part, of continuous hepatic intra-arterial infusion therapy with 5-fluorouracil, mitoxantrone and cisplatin (FMP therapy) in patients with advanced hepatocellular carcinoma (HCC). Methods: Forty-five patients with advanced HCC were enrolled. The therapy consisted of continuous intra-arterial infusion of 5-fluorouracil from Day 1 through Day 5, and intra-arterial administration of mitoxantrone and cisplatin on Day 1 [5-fluorouracil/mitoxantrone/cisplatin (mg/m2): Level 1; 400/4/60, Level 2; 400/6/60, Level 3; 500/6/60]...
March 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28330462/prospective-phase-ii-trial-of-everolimus-in-pik3ca-amplification-mutation-and-or-pten-loss-patients-with-advanced-solid-tumors-refractory-to-standard-therapy
#7
Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Won Ki Kang, Ho Yeong Lim
BACKGROUND: We designed a single-arm, open-label phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy (#NCT02449538). METHODS: Everolimus was administered orally at a daily dose of 10 mg continuously (28-day cycles). Treatment was continued until progression of the disease or intolerable toxicity was observed. Based on Simon's two-stage optimal design, 10 patients were treated with everolimus during the first stage...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28327200/a-first-in-human-phase-1-study-of-a-hepcidin-monoclonal-antibody-ly2787106-in-cancer-associated-anemia
#8
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W Goldman, David A Smith, Christopher A Slapak, Robert L Ilaria, Ramon V Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L Tuttle, Yiu-Keung Lau, Eric J Roeland
BACKGROUND: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28327055/the-evaluation-of-the-anti-cancer-activity-of-ixazomib-on-caco2-colon-solid-tumor-cells-comparison-with-bortezomib
#9
Selin Engür, Miriş Dikmen
Proteasome inhibition has recently emerged as a clinically effective anticancer therapeutic approach. The first proteasome inhibitor, bortezomib (Velcade, PS-341), and new proteasome inhibitors including ixazomib have become more important in the development of targeted cancer therapies. Under physiological conditions, MLN9708 (ixazomib citrate), the stable citrate ester drug substance, hydrolyzes rapidly to MLN2238 (ixazomib), the biologically active boronic acid. It is a second-generation proteasome inhibitor, similar to the well-known proteasome inhibitor bortezomib, which is currently being investigated in phase 3 trials as a treatment for multiple Myeloma...
March 22, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28314319/multicenter-phase-ii-clinical-trial-of-genexol-pm%C3%A2-with-gemcitabine-in-advanced-biliary-tract-cancer
#10
Jin Young Kim, Young Rok DO, Hong Suk Song, Yoon Young Cho, Hun Mo Ryoo, Sung Hwa Bae, Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, Jin Ho Baek, Min Kyoung Kim, Kyung Hee Lee, Keonuk Park
This multicenter phase II clinical trial was designed to evaluate the efficacy and safety of weekly Genexol-PM® and gemcitabine combination chemotherapy in patients with unresectable or metastatic biliary tract cancer. PATIENTS AND METHODS: Patients received 100 mg/m(2) Genexol-PM® and 1,000 mg/m(2) gemcitabine intravenously on days 1 and 8 every 21 days. RESULTS: Out of 39 patients, there were 10 partial responses (25.6%) and 18 with stable diseases (46.2%) were confirmed with median response duration 4...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28286420/hlbt-100-a-highly-potent-anti-cancer-flavanone-from-tillandsia-recurvata-l-l
#11
Henry I C Lowe, Ngeh J Toyang, Charah T Watson, Kenneth N Ayeah, Joseph Bryant
BACKGROUND: The incidence and mortalities from cancers remain on the rise worldwide. Despite significant efforts to discover and develop novel anticancer agents, many cancers remain in the unmet need category. As such, efforts to discover and develop new and more effective and less toxic agents against cancer remain a top global priority. Our drug discovery approach is natural products based with a focus on plants. Tillandsia recurvata (L.) L. is one of the plants selected by our research team for further studies based on previous bioactivity findings on the anticancer activity of this plant...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28280972/pemetrexed-monotherapy-for-chemo-na%C3%A3-ve-elderly-aged-%C3%A2-80-patients-with-non-squamous-non-small-cell-lung-cancer-results-from-combined-analysis-of-two-single-arm-phase-ii-studies-hanshin002-and-003
#12
Akito Hata, Nobuyuki Katakami, Yoshihiro Hattori, Kosuke Tanaka, Shiro Fujita, Yoshikazu Kotani, Takashi Nishimura, Fumio Imamura, Soichiro Yokota, Miyako Satouchi, Kazuya Monden, Kojiro Otsuka, Akihiro Nishiyama, Kazuya Tsubouchi, Toshihiko Kaneda, Hiroshige Yoshioka, Satoshi Morita, Shunichi Negoro
PURPOSE: The aim of this retrospective study was to evaluate via combined analysis the efficacy and safety of pemetrexed monotherapy for chemo-naïve elderly patients aged ≥80 with non-squamous non-small cell lung cancer (NSCLC). METHODS: We conducted a combined analysis from two phase II studies of pemetrexed for chemo-naïve elderly (aged ≥75) (n = 47) and performance status 2 (n = 28) patients with advanced non-squamous NSCLC. Population aged ≥80 (80+ Group) was compared to those aged 70-79 (70's Group)...
March 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28271997/a-retrospective-study-of-clinical-profile-and-long-term-outcome-to-imatinib-mesylate-alone-in-childhood-chronic-myeloid-leukemia-in-chronic-phase
#13
(no author information available yet)
OBJECTIVE: Chronic myeloid leukemia (CML) is relatively rare malignancy in childhood. There are limited studies of use of Imatinib Mesylate (IM) alone in management of CML in this age group. METHOD: We retrospectively analyzed the outcome of 30 consecutive children with CML chronic phase treated with IM alone. RESULTS: The median age at the time of diagnosis was 11 years with male preponderance. Asthenia and abdominal discomfort due to splenomegaly were the most common presenting features and splenomegaly a dominant sign...
January 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28268074/safety-and-immunogenicity-of-inactivated-varicella-zoster-virus-vaccine-in-adults-with-hematologic-malignancies-receiving-treatment-with-anti-cd20-monoclonal-antibodies
#14
Janie Parrino, Shelly A McNeil, Steven J Lawrence, Eva Kimby, Marco F Pagnoni, Jon E Stek, Yanli Zhao, Ivan S F Chan, Susan S Kaplan
BACKGROUND: Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVIN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80)...
March 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28265009/preclinical-mammalian-safety-studies-of-epharna-dopc-nanoliposomal-epha2-targeted-sirna
#15
Michael J Wagner, Rahul Mitra, Mark J McArthur, Wallace Baze, Kirstin Barnhart, Sherry Wu, Cristian Rodriguez-Aguayo, Xinna Zhang, Robert L Coleman, Gabriel Lopez-Berestein, Anil K Sood
To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N=15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model...
March 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28263212/a-phase-1-trial-of-cabazitaxel-combined-with-188-re-hydroxyethylidene-diphosphonate-in-patients-with-metastatic-castration-resistant-prostate-cancer-who-progressed-on-or-after-a-docetaxel-containing-treatment-the-recab-trial
#16
Joyce M van Dodewaard-de Jong, Esther W Bouman-Wammes, Haiko J Bloemendal, Henk M W Verheul, John M H de Klerk, Alfons J M van den Eertwegh
PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as Re-hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with Re-HEDP and cabazitaxel in mCRPC patients. METHODS: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion...
March 3, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28258828/dna-thioguanine-nucleotide-concentration-and-relapse-free-survival-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukaemia-nopho-all2008-a-prospective-substudy-of-a-phase-3-trial
#17
Stine Nygaard Nielsen, Kathrine Grell, Jacob Nersting, Jonas Abrahamsson, Bendik Lund, Jukka Kanerva, Ólafur Gísli Jónsson, Goda Vaitkeviciene, Kaie Pruunsild, Lisa Lyngsie Hjalgrim, Kjeld Schmiegelow
BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. METHODS: In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia...
February 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28249141/blinatumomab-versus-chemotherapy-for-advanced-acute-lymphoblastic-leukemia
#18
RANDOMIZED CONTROLLED TRIAL
Hagop Kantarjian, Anthony Stein, Nicola Gökbuget, Adele K Fielding, Andre C Schuh, Josep-Maria Ribera, Andrew Wei, Hervé Dombret, Robin Foà, Renato Bassan, Önder Arslan, Miguel A Sanz, Julie Bergeron, Fatih Demirkan, Ewa Lech-Maranda, Alessandro Rambaldi, Xavier Thomas, Heinz-August Horst, Monika Brüggemann, Wolfram Klapper, Brent L Wood, Alex Fleishman, Dirk Nagorsen, Christopher Holland, Zachary Zimmerman, Max S Topp
Background Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. Methods In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy...
March 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28243182/laquinimod-safety-profile-pooled-analyses-from-the-allegro-and-bravo-trials
#19
Per Soelberg Sørensen, Giancarlo Comi, Timothy L Vollmer, Xavier Montalban, Ludwig Kappos, Yuval Dadon, Tali Gorfine, Maya Margalit, Nissim Sasson, Svetlana Rubinchick, Volker Knappertz
BACKGROUND: Laquinimod 0.6 mg is a once-daily, oral, disease-modifying therapy in development for the treatment of multiple sclerosis (MS) that was investigated in two double-blind, placebo-controlled, phase 3 trials: ALLEGRO and BRAVO. METHODS: Data from these studies were pooled to assess the safety profile of laquinimod versus placebo. Adverse events (AEs), laboratory value changes, and potential risks identified in preclinical studies were evaluated in participants in ALLEGRO and BRAVO treated with at least one dose of laquinimod or matching placebo (1:1 random assignment)...
January 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/28238078/phase-i-study-of-pazopanib-plus-th-302-in-advanced-solid-tumors
#20
Richard F Riedel, Kellen L Meadows, Paula H Lee, Michael A Morse, Hope E Uronis, Gerard C Blobe, Daniel J George, Jeffrey Crawford, Donna Niedzwiecki, Christel N Rushing, Christy C Arrowood, Herbert I Hurwitz
PURPOSE: To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced solid tumors. METHODS: This was an open-label, non-randomized, single-center, phase I trial consisting 2 stages. Stage 1 was a standard "3 + 3" dose escalation design to determine safety and the RPTD for TH-302 plus pazopanib combination...
February 25, 2017: Cancer Chemotherapy and Pharmacology
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