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https://www.readbyqxmd.com/read/27914241/engot-ov-6-trinova-2-randomised-double-blind-phase-3-study-of-pegylated-liposomal-doxorubicin-plus-trebananib-or-placebo-in-women-with-recurrent-partially-platinum-sensitive-or-resistant-ovarian-cancer
#1
Christian Marth, Ignace Vergote, Giovanni Scambia, Willi Oberaigner, Andrew Clamp, Regina Berger, Christian Kurzeder, Nicoletta Colombo, Peter Vuylsteke, Domenica Lorusso, Marcia Hall, Vincent Renard, Sandro Pignata, Rebecca Kristeleit, Sevilay Altintas, Gordon Rustin, Robert M Wenham, Mansoor Raza Mirza, Peter C Fong, Amit Oza, Bradley J Monk, Haijun Ma, Florian D Vogl, Bruce A Bach
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m(2) once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo...
November 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#2
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27906967/platinum-ii-iodido-complexes-of-7-azaindoles-with-significant-antiproliferative-effects-an-old-story-revisited-with-unexpected-outcomes
#3
Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Jan Hošek, Jarmila Klusáková, Zdeněk Dvořák
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin...
2016: PloS One
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#4
Jean-Pascal Henry Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
November 30, 2016: Oncologist
https://www.readbyqxmd.com/read/27903751/microdose-induced-drug-dna-adducts-as-biomarkers-of-chemotherapy-resistance-in-humans-and-mice
#5
Maike Zimmermann, Si-Si Wang, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W Turteltaub, George D Cimino, Clifford G Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#6
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27897281/platinum-ii-o-s-complexes-as-potential-metallodrugs-against-cisplatin-resistance
#7
Jana Hildebrandt, Norman Häfner, Helmar Görls, Daniel Kritsch, Giarita Ferraro, Matthias Dürst, Ingo B Runnebaum, Antonello Merlino, Wolfgang Weigand
We report on platinum(ii) complexes with different cinnamic acid derivatives as ligands with cytotoxic activity against Cisplatin resistant ovarian cancer cell line subcultures of SKOV3 and A2780. A typical mechanism of action for platinum(ii) complexes as Cisplatin itself is binding to the DNA and inducing double-strand breaks. We examined the biological behavior of these potential drugs with 9-methylguanine using NMR spectroscopic methods and their DNA damage potential including γH2AX-foci analyses. X-ray diffraction methods have been used to elucidate the molecular structures of the platinum(ii) complexes...
November 29, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27895753/drug-resistance-analysis-of-gefitinib-targeted-therapy-in-non-small-cell-lung-cancer
#8
Shuliang Liu, Hongji Yang, Xingping Ge, Lingfei Su, Aifeng Zhang, Liang Liang
The aim of the study was to examine the drug resistance analysis of gefitinib-targeted therapy in non-small cell lung cancer (NSCLC). In total, 156 NSCLC patients without surgical treatment were selected, including 117 cases of adenocarcinoma (75%), to receive single gefitinib 0.25 g/day or combined with platinum chemotherapy. Computed tomography was used to evaluate tumor growth for the response and non-response groups. The chemotherapy regimen was changed or combined with radiotherapy in the non-response group...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894751/polymerase-%C3%AE%C2%B5-pole-ultra-mutation-in-uterine-tumors-correlates-with-t-lymphocyte-infiltration-and-increased-resistance-to-platinum-based-chemotherapy-in-vitro
#9
Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger, Pei Hui, Salvatore Lopez, Christopher de Haydu, Elena Bonazzoli, Federica Predolini, Luca Zammataro, Emiliano Cocco, Federico Ferrari, Antonella Ravaggi, Chiara Romani, Fabio Facchetti, Enrico Sartori, Franco E Odicino, Dan-Arin Silasi, Babak Litkouhi, Elena Ratner, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC...
November 25, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27893326/randomized-prospective-biomarker-trial-of-ercc1-for-comparing-platinum-and-nonplatinum-therapy-in-advanced-non-small-cell-lung-cancer-ercc1-trial-et
#10
Siow Ming Lee, Mary Falzon, Fiona Blackhall, James Spicer, Marianne Nicolson, Abhro Chaudhuri, Gary Middleton, Samreen Ahmed, Jonathan Hicks, Barbara Crosse, Mark Napier, Julian M Singer, David Ferry, Conrad Lewanski, Martin Forster, Sally-Ann Rolls, Arrigo Capitanio, Robin Rudd, Natasha Iles, Yenting Ngai, Michael Gandy, Rachel Lillywhite, Allan Hackshaw
Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27889646/mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-potentiates-the-activity-of-standard-of-care-therapeutics-in-ovarian-cancer-models
#11
Jose F Ponte, Olga Ab, Leanne Lanieri, Jenny Lee, Jennifer Coccia, Laura M Bartle, Marian Themeles, Yinghui Zhou, Jan Pinkas, Rodrigo Ruiz-Soto
Elevated folate receptor alpha (FRα) expression is characteristic of epithelial ovarian cancer (EOC), thus establishing this receptor as a candidate target for the development of novel therapeutics to treat this disease. Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FRα for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics. Here, combinations of IMGN853 with approved therapeutics were evaluated in preclinical models of EOC...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27888804/niclosamide-and-its-analogs-are-potent-inhibitors-of-wnt-%C3%AE-catenin-mtor-and-stat3-signaling-in-ovarian-cancer
#12
Rebecca C Arend, Angelina I Londoño-Joshi, Abhishek Gangrade, Ashwini A Katre, Chandrika Kurpad, Yonghe Li, Rajeev S Samant, Pui-Kai Li, Charles N Landen, Eddy S Yang, Bertha Hidalgo, Ronald D Alvarez, J Michael Straughn, Andres Forero, Donald J Buchsbaum
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. Platinum-based therapy is the standard first line treatment and while most patients initially respond, resistance to chemotherapy usually arises. Major signaling pathways frequently upregulated in chemoresistant cells and important in the maintenance of cancer stem cells (CSCs) include Wnt/β-catenin, mTOR, and STAT3. The major objective of our study was to investigate the treatment of ovarian cancer with targeted agents that inhibit these three pathways...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#13
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887849/inhibition-of-heat-shock-protein-hsp-90-potentiates-the-antiproliferative-and-pro-apoptotic-effects-of-2-4-fluoro-phenylamino-4h-1-3-thiazine-6-5-b-indole-in-a2780cis-cells
#14
Zuzana Solárová, Martin Kello, Lenka Varinská, Mariana Budovská, Peter Solár
Ovarian carcinoma is initially sensitive to platinum-based therapy, but become resistant over time. The study of cancer sensitizing substance is therefore the major challenge for a number of scientific groups. Our experiments were carried out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation assay, cell cycle analysis and monitoring of apoptosis were examined...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27884789/surgery-for-advanced-epithelial-ovarian-cancer
#15
REVIEW
Neville F Hacker, Archana Rao
Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational...
October 20, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/27882231/organic-cation-transporter-6-directly-confers-resistance-to-anticancer-platinum-drugs
#16
Tetsuya Oguri, Eiji Kunii, Satoshi Fukuda, Kazuki Sone, Takehiro Uemura, Osamu Takakuwa, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Ken Maeno, Yutaka Ito, Akio Niimi
Organic cation transporters (OCTs) of the solute carrier family 22 have a critical role in the cellular uptake of anticancer platinum drugs. Recently, we found that a decreased OCT6 expression is associated with a reduced intracellular uptake of cisplatin (CDDP), and concomitant resistance to CDDP. In the present study, we examined whether OCTs directly confer resistance to another platinum drug, oxaliplatin (L-OHP). To address this, we used parental lung cancer cell lines, PC-14 and SBC3; L-OHP-resistant sublines, PC-14/L-OHP and SBC3/L-OHP; and one CDDP-resistant subline PC-14/CDDP, to examine the relationships between the expression of OCTs and intracellular platinum drug concentration or platinum drug resistance...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27878277/synthetic-paclitaxel-octreotide-conjugate-reverses-the-resistance-of-paclitaxel-in-a2780-taxol-ovarian-cancer-cell-line
#17
Yang Shen, Xiao-Yu Zhang, Xi Chen, Li-Li Fan, Mu-Lan Ren, Yong-Ping Wu, Kenneth Chanda, Shi-Wen Jiang
The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27877224/the-role-of-copper-transporter-atp7a-in-platinum-resistance-of-esophageal-squamous-cell-cancer-escc
#18
Zhuang-Hua Li, Rongjie Zheng, Jing-Tang Chen, Jun Jia, Miaozhen Qiu
Purpose: Platinum derivatives, such as cisplatin (DDP), carboplatin and oxaliplatin, are widely used components of modern cancer chemotherapy including esophageal squamous cell cancer (ESCC). However, their roles are limited by the impact of intrinsic/acquired resistance mechanisms on tumor responses. Recent studies have shown that the mammalian copper transporters CTR1, ATP7A and ATP7B are involved in cisplatin-resistance to some cancers. Methods: The cytotoxicities of DDP in different cell lines were determined using the MTT assay...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27872093/a-novel-platinum-ii-based-bifunctional-adc-linker-benchmarked-using-89zr-desferal-and-auristatin-f-conjugated-trastuzumab
#19
Niels J Sijbrandi, Eugen Merkul, Joey A Muns, Dennis Cj Waalboer, Kevin Adamzek, Marije Bolijn, Veronica Montserrat, Govert W Somsen, Rob Haselberg, Paul Jgm Steverink, Hendrik-Jan Houthoff, Guus A M S van Dongen
Greater control is desirable in the stochastic conjugation technology used to synthesize antibody-drug conjugates (ADCs). We have shown recently that a fluorescent dye can be stably conjugated to a monoclonal antibody (mAb) using a bifunctional platinum(II) linker. Here we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamineplatinum(II) moiety, herein called Lx®, was coordinated to Desferal® (DFO) or auristatin F (AF) to provide storable "semi-final" products, which were directly conjugated to unmodified mAbs...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27871723/safety-and-efficacy-of-single-agent-bevacizumab-containing-therapy-in-elderly-patients-with-platinum-resistant-recurrent-ovarian-cancer-subgroup-analysis-of-the-randomised-phase-iii-aurelia-trial
#20
Roberto Sorio, Célia Roemer-Becuwe, Felix Hilpert, Emma Gibbs, Yolanda García, Janne Kaern, Manon Huizing, Petronella Witteveen, Flora Zagouri, David Coeffic, Hans-Joachim Lück, Antonio González-Martín, Gunnar Kristensen, Charles-Briac Levaché, Chee Khoon Lee, Val Gebski, Eric Pujade-Lauraine
BACKGROUND: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). METHODS: Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years. RESULTS: In the 133 patients (37%) aged ≥65years, baseline hypertension was more frequent and ascites was less common than in patients <65years...
November 18, 2016: Gynecologic Oncology
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