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Investigational New Drugs

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https://www.readbyqxmd.com/read/28819760/effect-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-on-the-qtc-interval-in-patients-with-advanced-malignancies
#1
Xiaofei Zhou, John Nemunaitis, Shubham Pant, Todd M Bauer, Manish Patel, John Sarantopoulos, A Craig Lockhart, Daniel Goodman, Dirk Huebner, Diane R Mould, Karthik Venkatakrishnan
Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 mg twice daily [BID] for 7 days in 21-day cycles). Methods Patients received a single dose of alisertib (50 mg) on Day 1, and multiple doses of alisertib (50 mg BID) on Days 4 through to the morning of Day 10 of the first cycle of treatment...
August 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#2
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#3
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28782087/germline-brca-mutations-in-asian-patients-with-pancreatic-adenocarcinoma-a-prospective-study-evaluating-risk-category-for-genetic-testing
#4
Kyoungmin Lee, Changhoon Yoo, Kyu-Pyo Kim, Kyoung-Jin Park, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee, Woochang Lee, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Song Cheol Kim, Baek-Yeol Ryoo
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy...
August 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28776290/synthesis-characterization-and-evaluation-of-cd-l-proline-2-a-novel-histone-deacetylase-inhibitor-that-induces-epigenetic-modification-of-histone-deacetylase-isoforms-in-a549-cells
#5
Anusha Chidambaram, Arunachalam Sekar, Kavya S H, Ramesh Kumar Chidambaram, Kalaiarasi Arunachalam, Senthilkumar G P, Ravikumar Vilwanathan
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium-proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis...
August 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28762171/addition-of-an-antiangiogenic-therapy-bevacizumab-to-gemcitabine-plus-oxaliplatin-improves-survival-in-advanced-biliary-tract-cancers
#6
Marie Bréchon, Marie Dior, Johann Dréanic, Bertrand Brieau, Marie-Anne Guillaumot, Catherine Brezault, Olivier Mir, François Goldwasser, Romain Coriat
Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared...
August 1, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28752433/a-phase-i-study-to-determine-safety-pharmacokinetics-and-pharmacodynamics-of-anf-rho%C3%A2-a-novel-pegylated-granulocyte-colony-stimulating-factor-in-healthy-volunteers
#7
Hemant Misra, John Berryman, Ronald Jubin, Abraham Abuchowski
Patients receiving pegfilgrastim (Neulasta®) for the treatment of neutropenia can experience bone pain following the injections required to achieve effective neutrophil levels. The safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of ANF-RHO™, a novel pegylated granulocyte colony stimulating factor, were assessed in a randomized, controlled, double-blind Phase 1 clinical study in healthy volunteers. Subjects received a single subcutaneous dose of ANF-RHO over a range of 6 doses (5-50 μg/kg), placebo (saline), or the recommended clinical dose of pegfilgrastim administered at the labeled fixed 6 mg dosage (equivalent to 80-100 μg/kg)...
July 28, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733703/induction-of-accelerated-senescence-by-the-microtubule-stabilizing-agent-peloruside-a
#8
Ariane Chan, Connie Gilfillan, Nikki Templeton, Ian Paterson, Peter T Northcote, John H Miller
Chemotherapeutic agents can induce accelerated senescence in tumor cells, an irreversible state of cell cycle arrest. Paclitaxel, a microtubule-stabilizing agent used to treat solid tumors of the breast, ovary, and lung and discodermolide, another stabilizing agent from a marine sponge, induce senescence in cultured cancer cells. The aim of this study was to determine if the microtubule-stabilizing agent peloruside A, a polyketide natural product from a marine sponge, can induce accelerated senescence in a breast cancer cell line MCF7...
July 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733702/anti-invasive-effects-of-cxcr4-and-fak-inhibitors-in-non-small-cell-lung-carcinomas-with-mutually-inactivated-p53-and-pten-tumor-suppressors
#9
Miodrag Dragoj, Jasna Bankovic, Evangelia Sereti, Sofija Jovanovic Stojanov, Konstantinos Dimas, Milica Pesic, Tijana Stankovic
Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs...
July 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733701/copper-ii-complexes-of-bidentate-ligands-exhibit-potent-anti-cancer-activity-regardless-of-platinum-sensitivity-status
#10
Mohamed Wehbe, Cody Lo, Ada W Y Leung, Wieslawa H Dragowska, Gemma M Ryan, Marcel B Bally
Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50 ~ 1 μM platinum) and insensitive (IC50 > 5 μM platinum) cell lines...
July 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733700/feasibility-of-olanzapine-multi-acting-receptor-targeted-antipsychotic-agent-for-the-prevention-of-emesis-caused-by-continuous-cisplatin-or-ifosfamide-based-chemotherapy
#11
Seiko Bun, Kan Yonemori, Toru Akagi, Emi Noguchi, Tatsunori Shimoi, Akihiko Shimomura, Mayu Yunokawa, Chikako Shimizu, Yasuhiro Fujiwara, Yoshinori Makino, Yoshikazu Hayashi, Kenji Tamura
Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP)...
July 21, 2017: Investigational New Drugs
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
#12
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/28676972/erratum-to-a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#13
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
No abstract text is available yet for this article.
July 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28660549/safety-and-effectiveness-of-eribulin-in-japanese-patients-with-locally-advanced-or-metastatic-breast-cancer-a-post-marketing-observational-study
#14
Junichiro Watanabe, Yoshinori Ito, Shozo Ohsumi, Mitsuhiro Mizutani, Hideya Tashiro, Kenichi Sakurai, Masato Takahashi, Tsuyoshi Saito, Junji Tsurutani, Hirofumi Mukai, Tetsuhiro Yoshinami, Shintaro Takao, Yasuhisa Yamamoto, Toshiyuki Matsuoka, Hirotaka Iwase, Hiroji Iwata, Seigo Nakamura, Toshiaki Saeki
Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m(2)) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs)...
June 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28660548/chemotherapy-induced-cardiomyopathy-caused-by-pemetrexed
#15
Takuya Oyakawa, Kei Iida, Masatoshi Kusuhara, Hirotsugu Kenmotsu, Takashi Sugino
Chemotherapy-related cardiac toxicity is a rare but serious adverse event in patients with cancer. Thus far, no case of serious cardiac toxicity of pemetrexed has been reported. We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3 weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks...
June 28, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28631098/urolithins-impair-cell-proliferation-arrest-the-cell-cycle-and-induce-apoptosis-in-umuc3-bladder-cancer-cells
#16
Joana Liberal, Anália Carmo, Célia Gomes, Maria Teresa Cruz, Maria Teresa Batista
Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28631097/phase-ii-study-of-amrubicin-monotherapy-in-elderly-or-poor-risk-patients-with-extensive-disease-of-small-cell-lung-cancer
#17
Satoshi Igawa, Sakiko Otani, Shinichiro Ryuge, Tomoya Fukui, Yoshiro Nakahara, Yasuhiro Hiyoshi, Mikiko Ishihara, Seiichiro Kusuhara, Shinya Harada, Hisashi Mitsufuji, Masaru Kubota, Jiichiro Sasaki, Noriyuki Masuda
Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m(2) amrubicin for 3 consecutive days every 21 days...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28631096/a-case-of-nivolumab-related-cholangitis-and-literature-review-how-to-look-for-the-right-tools-for-a-correct-diagnosis-of-this-rare-immune-related-adverse-event
#18
Francesco Gelsomino, Giovanni Vitale, Andrea Ardizzoni
Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28631095/decorin-gene-upregulation-mediated-by-an-adeno-associated-virus-vector-increases-intratumoral-uptake-of-nab-paclitaxel-in-neuroblastoma-via-inhibition-of-stabilin-1
#19
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu
The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28616837/a-phase-ib-study-of-everolimus-combined-with-metformin-for-patients-with-advanced-cancer
#20
Remco J Molenaar, Tim van de Venne, Mariëtte J Weterman, Ron A Mathot, Heinz-Josef Klümpen, Dick J Richel, Johanna W Wilmink
Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78)...
June 15, 2017: Investigational New Drugs
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