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https://www.readbyqxmd.com/read/28632487/prospective-randomized-comparison-of-idarubicin-and-high-dose-daunorubicin-in-induction-chemotherapy-for-newly-diagnosed-acute-myeloid-leukemia
#1
Je-Hwan Lee, Hawk Kim, Young-Don Joo, Won-Sik Lee, Sung Hwa Bae, Dae Young Zang, Jihyun Kwon, Min Kyoung Kim, Junglim Lee, Gyeong Won Lee, Jung-Hee Lee, Yunsuk Choi, Dae-Young Kim, Eun-Hye Hur, Sung-Nam Lim, Sang-Min Lee, Hun Mo Ryoo, Hyo Jung Kim, Myung Soo Hyun, Kyoo-Hyung Lee
Purpose We compared two induction regimens, idarubicin (12 mg/m(2)/d for 3 days) versus high-dose daunorubicin (90 mg/m(2)/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m(2)/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28630120/selinexor-induced-thrombocytopenia-results-from-inhibition-of-thrombopoietin-signaling-in-early-megakaryopoiesis
#2
Kellie R Machlus, Stephen K Wu, Prakrith Vijey, Thomas S Soussou, Zhi-Jian Liu, Eran Shacham, T J Unger, Trinayan Kashyap, Boris Klebanov, Martha Sola-Visner, Marsha Crochiere, Joseph E Italiano, Yosef Landesman
Selinexor is the first oral Selective Inhibitor of Nuclear Export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (NCT03071276, NCT02343042, NCT02227251, NCT03110562, NCT02606461). While selinexor shows promising efficacy, its primary adverse effect is high-grade thrombocytopenia. Therefore, we aimed to identify the mechanism of selinexor-induced thrombocytopenia to relieve it and improve its clinical management...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28628416/case-243-extramedullary-hematopoiesis-in-an-adrenal-myelolipoma
#3
James Tanner, Shalini Malhotra, Hesham El-Daly, Edmund M Godfrey
History A 30-year-old man presented to the emergency department with epigastric pain. He was vomiting and in distress, and he had a history of thalassemia. Physical examination findings were unremarkable. Pertinent blood results were a hemoglobin level of 10.5 g/dL (6.52 mmol/L) (normal range, 13.5-18.0 g/dL [8.38-11.17 mmol/L]) and a bilirubin level of 62 µmol/L (normal range, 3-17 µmol/L). The remaining hematologic and biochemical results were normal. Aortic dissection was suspected clinically, so the patient was referred for imaging...
July 2017: Radiology
https://www.readbyqxmd.com/read/28620382/phase-ii-study-of-adjuvant-immunotherapy-with-the-csf-470-vaccine-plus-bacillus-calmette-guerin-plus-recombinant-human-granulocyte-macrophage-colony-stimulating-factor-vs-medium-dose-interferon-alpha-2b-in-stages-iib-iic-and-iii-cutaneous-melanoma-patients
#4
José Mordoh, María Betina Pampena, Mariana Aris, Paula Alejandra Blanco, Mónica Lombardo, Erika María von Euw, Soledad Mac Keon, Michelle Yépez Crow, Alicia Inés Bravo, Juan Manuel O'Connor, Ana Gabriela Orlando, Franco Ramello, Estrella Mariel Levy, María Marcela Barrio
The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (n = 20) or to the IFN-α2b arm (n = 11)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28610775/cytotoxic-effect-of-a-novel-naphthylchalcone-against-multiple-cancer-cells-focusing-on-hematologic-malignancies
#5
Mariana Franzoni Maioral, Camila do Nascimento Bodack, Natália Marceli Stefanes, Álisson Bigolin, Alessandra Mascarello, Louise Domeneghini Chiaradia-Delatorre, Rosendo Augusto Yunes, Ricardo José Nunes, Maria Cláudia Santos-Silva
Chalcones are natural compounds described in the literature by its several properties including cytotoxic activity against several tumor types. Considering that the search for new chemotherapeutic agents is still necessary, the aim of this study was to investigate the cytotoxic mechanisms involved in cell death induced by a synthetic chalcone (A23) on different tumor cells. Chalcone A23 reduced the cell viability of twelve tumor cell lines in a concentration and time dependent manner and it was more cytotoxic against acute leukemia cells...
June 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28607470/a-phase-ii-multicentre-trial-of-decitabine-in-higher-risk-chronic-myelomonocytic-leukemia
#6
V Santini, B Allione, G Zini, D Gioia, M Lunghi, A Poloni, D Cilloni, A Sanna, E Masiera, M Ceccarelli, O Abdel-Wahab, A Terenzi, E Angelucci, C Finelli, F Onida, A M Pelizzari, D Ferrero, G Saglio, M Figueroa, A Levis
Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received i.v. decitabine 20 mg/m(2)/day on Days 1 to 5 of a 28-day treatment cycle...
June 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28605730/gemcitabine-and-vinorelbine-combination-chemotherapy-in-taxane-pretreated-patients-with-metastatic-breast-cancer-a-phase-ii-study-of-the-kinki-multidisciplinary-breast-oncology-group-kmbog-1015
#7
Jun Yamamura, Norikazu Masuda, Daigo Yamamoto, Shigeru Tsuyuki, Masahide Yamaguchi, Satoru Tanaka, Junji Tsurutani, Shinya Tokunaga, Katsuhide Yoshidome, Makiko Mizutani, Toyokazu Aono, Asako Ooe, Hirokazu Tanino, Nobuki Matsunami, Hiroyuki Yasojima, Takahiro Nakayama, Yukihiro Nishida
BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety...
June 13, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28597723/minimal-activity-of-nanoparticle-albumin-bound-nab-paclitaxel-in-relapsed-or-refractory-lymphomas-results-of-a-phase-i-study
#8
Sagun Goyal, Eunhye Oak, Jingqin Luo, Amanda F Cashen, Kenneth Carson, Todd Fehniger, John DiPersio, Nancy L Bartlett, Nina D Wagner-Johnston
Compared with solvent-based taxanes, nanoparticle albumin-bound (nab(®)) paclitaxel has demonstrated improved efficacy and tolerability in several solid tumor malignancies. Studies evaluating nab paclitaxel in patients with lymphoma are lacking. In this planned phase-I/phase-II study, we sought to determine the safety and efficacy of nab-paclitaxel in patients with relapsed/refractory (R/R) lymphoma. Eligible patients (R/R to ≥2 prior systemic therapies) received weekly nab-paclitaxel on days 1, 8 and 15 every 28 days...
June 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28592624/prolonged-pemetrexed-infusion-plus-gemcitabine-in-refractory-metastatic-colorectal-cancer-preclinical-rationale-and-phase-ii-study-results
#9
Alessandro Passardi, Francesca Fanini, Livia Turci, Flavia Foca, Paola Rosetti, Silvia Ruscelli, Andrea Casadei Gardini, Martina Valgiusti, Claudio Dazzi, Maurizio Marangolo
LESSONS LEARNED: Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged. BACKGROUND: We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28592260/recent-advances-in-the-use-of-pi3k-inhibitors-for-glioblastoma-multiforme-current-preclinical-and-clinical-development
#10
REVIEW
Hua-Fu Zhao, Jing Wang, Wei Shao, Chang-Peng Wu, Zhong-Ping Chen, Shing-Shun Tony To, Wei-Ping Li
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism...
June 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#11
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stéphane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ~12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, leading to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human, phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28581468/a-phase-i-ii-minor-histocompatibility-antigen-loaded-dendritic-cell-vaccination-trial-to-safely-improve-the-efficacy-of-donor-lymphocyte-infusions-in-myeloma
#12
L E Franssen, M W H Roeven, W Hobo, R Doorn, R Oostvogels, J H F Falkenburg, N W van de Donk, M G D Kester, H Fredrix, K Westinga, I Slaper-Cortenbach, E Spierings, M J Kersten, H Dolstra, T Mutis, N Schaap, H M Lokhorst
Allogeneic stem cell transplantation (allo-SCT) with or without donor lymphocyte infusions (DLI) is the only curative option for several hematological malignancies. Unfortunately, allo-SCT is often associated with GvHD, and patients often relapse. We therefore aim to improve the graft-versus-tumor effect, without increasing the risk of GvHD, by targeting hematopoietic lineage-restricted and tumor-associated minor histocompatibility antigens using peptide-loaded dendritic cell (DC) vaccinations. In the present multicenter study, we report the feasibility, safety and efficacy of this concept...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28574931/neoadjuvant-weekly-paclitaxel-carboplatin-is-effective-in-stage-i-ii-cervical-cancer
#13
Rawand Salihi, Karin Leunen, Philippe Moerman, Frédéric Amant, Patrick Neven, Ignace Vergote
OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by surgery in cervical cancer is widely studied with paclitaxel-ifosfamide-cisplatinum 3 weekly (TIP). Although the response rates with TIP are high, the toxicity is substantial. Therefore, this study evaluates dose-dense paclitaxel-carboplatin (TC) as an alternative. METHODS: In this prospective phase 2 study trial, we included 36 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 to IIB cervical cancer, who received 9 weeks' NACT dose-dense TC (median weekly dose paclitaxel 60 mg/m, carboplatinum area under the curve 2...
June 1, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28573252/induction-of-cell-cycle-arrest-and-apoptosis-by-ormenis-eriolepis-a-morrocan-endemic-plant-in-various-human-cancer-cell-lines
#14
Lamiae Belayachi, Clara Aceves-Luquero, Nawel Merghoub, Silvia Fernández de Mattos, Saaîd Amzazi, Priam Villalonga, Youssef Bakri
BACKGROUND: Ormenis eriolepis Coss (Asteraceae) is an endemic Moroccan subspecies, traditionally named "Hellala" or "Fergoga". It's usually used for its hypoglycemic effect as well as for the treatment of stomacal pain. As far as we know, there is no scientific exploration of anti tumoral activity of Ormenis eriolepis extracts. MATERIALS AND METHODS: In this regard, we performed a screening of organic extracts and fractions in a panel of both hematological and solid cancer cell lines, to evaluate the potential in vitro anti tumoral activity and to elucidate the respective mechanisms that may be responsible for growth arrest and cell death induction...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28556364/phase-i-study-of-glasdegib-pf-04449913-an-oral-smoothened-inhibitor-in-japanese-patients-with-select-hematologic-malignancies
#15
Yosuke Minami, Hironobu Minami, Toshihiro Miyamoto, Goichi Yoshimoto, Yukio Kobayashi, Wataru Munakata, Yasushi Onishi, Masahiro Kobayashi, Mari Ikuta, Geoffrey Chan, Adrian Woolfson, Chiho Ono, Mohammed Naveed Shaik, Yosuke Fujii, Xianxian Zheng, Tomoki Naoe
The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open-label, multicenter phase I trial of the selective, small-molecule hedgehog signaling inhibitor glasdegib (PF-04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once-daily oral doses (25, 50, and 100 mg) in 28-day cycles after a lead-in dose on Day -5...
May 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28550039/a-phase-1-2-study-of-the-oral-proteasome-inhibitor-ixazomib-in-relapsed-or-refractory-light-chain-al-amyloidosis
#16
Vaishali Sanchorawala, Giovanni Palladini, Vishal Kukreti, Jeffrey A Zonder, Adam D Cohen, David C Seldin, Angela Dispenzieri, Arnaud Jaccard, Stefan O Schönland, Deborah Berg, Huyuan Yang, Neeraj Gupta, Ai-Min Hui, Raymond L Comenzo, Giampaolo Merlini
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory AL amyloidosis (RRAL). Ixazomib was administered to adult patients with RRAL after ≥1 prior line of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naïve and PI-exposed patients) at the maximum tolerated dose (MTD)...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549771/calcineurin-and-mtor-inhibitor-free-post-transplantation-cyclophosphamide-and-bortezomib-combination-for-graft-versus-host-disease-prevention-after-peripheral-blood-allogeneic-hematopoietic-stem-cell-transplantation-a-phase-i-ii-study
#17
A Samer Al-Homsi, Kelli Cole, Marlee Muilenburg, Austin Goodyke, Muneer Abidi, Ulrich Duffner, Stephanie Williams, Jessica Parker, Aly Abdel-Mageed
Graft-versus-host disease (GVHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GVHD. Patients undergoing peripheral blood AHSCT for hematological malignancies after reduced-intensity conditioning with grafts from HLA-matched related or unrelated donors were enrolled in a phase I/II clinical trial...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28547525/neoadjuvant-chemotherapy-with-trastuzumab-docetaxel-and-carboplatin-administered-every-3%C3%A2-weeks-for-japanese-women-with-her2-positive-primary-breast-cancer-efficacy-and-safety
#18
Ikuko Sugitani, Shigeto Ueda, Takashi Sakurai, Takashi Shigekawa, Eiko Hirokawa, Hiroko Shimada, Hideki Takeuchi, Kazuo Matsuura, Misono Misumi, Nobuko Fujiuchi, Takao Takahashi, Takahiro Hasebe, Akihiko Osaki, Toshiaki Saeki
BACKGROUND: This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer. METHODS: Patients with HER2-positive, stage I-III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m(2), day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks...
May 25, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28536803/prospective-multicenter-phase-ii-study-of-gemcitabine-plus-cisplatin-in-patients-with-unresectable-gallbladder-cancer
#19
Yoshiki Hirooka, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Koji Nonogaki, Akira Kanamori, Takanori Hirai, Hiroki Uchida, Osamu Shirai, Hideki Ishikawa, Hidemi Goto
PURPOSE: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC). METHODS: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m(2)) and cisplatin (25 mg/m(2)) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]...
May 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28522573/lenalidomide-melphalan-dexamethasone-in-newly-diagnosed-patients-with-al-amyloidosis-results-of-a-prospective-phase-2-study-with-long-term-follow-up
#20
Ute Hegenbart, Tilmann Bochtler, Axel Benner, Natalia Becker, Christoph Kimmich, Arnt V Kristen, Jörg Beimler, Ernst Hund, Markus Zorn, Anja Freiberger, Marianne Gawlik, Hartmut Goldschmidt, Dirk Hose, Anna Jauch, Anthony D Ho, Stefan O Schönland
Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%)...
May 18, 2017: Haematologica
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