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https://www.readbyqxmd.com/read/29792572/galnac-sirna-conjugates-leading-the-way-for-delivery-of-rnai-therapeutics
#1
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29792122/drug-cost-avoidance-in-clinical-trials-of-breast-cancer
#2
M Mañes-Sevilla, R Romero-Jiménez, A Herranz-Alonso, M Sánchez-Fresneda, E Gonzalez-Haba, R Collado-Borrel, J Benedi-González, M Sanjurjo-Sáez
Background The objectives of this study were to determine if clinical trials in breast cancer, with an investigational drug, created direct drug cost savings for the healthcare system related to cost avoidance of the best standard of care treatments used in these studies. The aim was to quantify this potential drug cost avoidance. Methods We conducted a retrospective observational study of the drug cost avoidance during the study period (2014-2016). We included clinical trials with investigational drug, managed by pharmacy department and provided by the sponsor...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29790694/advances-in-antibody-therapeutics-targeting-small-cell-lung-cancer
#3
REVIEW
Hongyang Lu, Zhiming Jiang
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials...
May 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29789969/identification-of-risk-factors-for-toxicity-in-patients-with-hormone-receptor-positive-advanced-breast-cancer-treated-with-bevacizumab-plus-letrozole-a-calgb-40503-alliance-correlative-study
#4
Daneng Li, Linda M McCall, Olwen M Hahn, Clifford A Hudis, Harvey J Cohen, Hyman B Muss, Aminah Jatoi, Jacqueline M Lafky, Karla V Ballman, Eric P Winer, Debu Tripathy, Bryan Schneider, William Barry, Maura N Dickler, Arti Hurria
BACKGROUND: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. METHODS: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab...
May 22, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29789220/adaura-phase-iii-double-blind-randomized-study-of-osimertinib-versus-placebo-in-egfr-mutation-positive-early-stage-nsclc-after-complete-surgical-resection
#5
Yi-Long Wu, Roy S Herbst, Helen Mann, Yuri Rukazenkov, Marcelo Marotti, Masahiro Tsuboi
INTRODUCTION: Currently, the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as adjuvant therapy for early-stage non-small-cell lung cancer after complete surgical tumor resection remains under investigation. We present the rationale and study design for the ADAURA (ClinicalTrials.gov identifier, NCT02511106) trial, a multicenter, double-blind, randomized, placebo-controlled study. PATIENTS AND METHODS: Study entry will be limited to adults aged ≥ 18 years (and in Japan and Taiwan, age ≥ 20 years) with primary nonsquamous stage IB-IIIA non-small-cell lung cancer with central confirmation of an EGFR exon 19 deletion or L858R mutation...
May 1, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29787357/prophylactic-cranial-irradiation-versus-observation-in-radically-treated-stage-iii-non-small-cell-lung-cancer-a-randomized-phase-iii-nvalt-11-dlcrg-02-study
#6
Dirk De Ruysscher, Anne-Marie C Dingemans, John Praag, Jose Belderbos, Caroline Tissing-Tan, Judith Herder, Tjeerd Haitjema, Fred Ubbels, Frank Lagerwaard, Sherif Y El Sharouni, Jos A Stigt, Egbert Smit, Harm van Tinteren, Vincent van der Noort, Harry J M Groen
Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging-were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery...
May 22, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29787356/selection-of-optimal-adjuvant-chemotherapy-and-targeted-therapy-for-early-breast-cancer-asco-clinical-practice-guideline-focused-update
#7
Neelima Denduluri, Mariana Chavez-MacGregor, Melinda L Telli, Andrea Eisen, Stephanie L Graff, Michael J Hassett, Jamie N Holloway, Arti Hurria, Tari A King, Gary H Lyman, Ann H Partridge, Mark R Somerfield, Maureen E Trudeau, Antonio C Wolff, Sharon H Giordano
Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer...
May 22, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29785577/atezolizumab-a-review-in-previously-treated-advanced-non-small-cell-lung-cancer
#8
REVIEW
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29784193/adjuvant-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-a-systematic-review-and-pooled-analysis
#9
REVIEW
Maxine Sun, Lorenzo Marconi, Tim Eisen, Bernard Escudier, Rachel H Giles, Naomi B Haas, Lauren C Harshman, David I Quinn, James Larkin, Sumanta K Pal, Thomas Powles, Christopher W Ryan, Cora N Sternberg, Robert Uzzo, Toni K Choueiri, Axel Bex
CONTEXT: Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). OBJECTIVE: To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. EVIDENCE ACQUISITION: A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed...
May 18, 2018: European Urology
https://www.readbyqxmd.com/read/29784042/neoadjuvant-oxaliplatin-and-capecitabine-combined-with-bevacizumab-plus-radiotherapy-for-locally-advanced-rectal-cancer-results-of-a-single-institute-phase-ii-study
#10
Xin Yu, Qiao-Xuan Wang, Wei-Wei Xiao, Hui Chang, Zhi-Fan Zeng, Zhen-Hai Lu, Xiao-Jun Wu, Gong Chen, Zhi-Zhong Pan, De-Sen Wan, Pei-Rong Ding, Yuan-Hong Gao
BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer, reducing local recurrence but not distant metastasis. Intensified systemic therapy is warranted to reduce the risk of distant metastasis. The present study aimed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine (XELOX) combined with bevacizumab plus radiotherapy for locally advanced rectal cancer. METHODS: Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus bevacizumab...
May 21, 2018: Cancer communications
https://www.readbyqxmd.com/read/29782648/patient-preferences-for-topical-treatment-of-actinic-keratoses-a-discrete-choice-experiment
#11
D Kopasker, A Kwiatkowski, R N Matin, C A Harwood, F Ismail, J T Lear, J Thomson, Z Hasan, G N Wali, A Milligan, L Crawford, I Ahmed, H Duffy, C M Proby, P F Allanson
BACKGROUND: Treatment of actinic keratoses (AK) is a potentially effective strategy for prevention of cutaneous squamous cell carcinoma (cSCC). However, the patient perspective on potential benefits of AK treatment in terms of skin cancer reduction has received little attention to date. OBJECTIVES: (1) To investigate patient preferences for AK topical treatments using a discrete choice experiment (DCE); (2) To evaluate patient willingness to trade between clinical benefit and medical burden...
May 21, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#12
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29777404/randomized-trial-comparing-resection-of-primary-tumor-with-no-surgery-in-stage-iv-breast-cancer-at-presentation-protocol-mf07-01
#13
Atilla Soran, Vahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Muslumanoglu, Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel, Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Betül Bozkurt, Ali Uzunkoy, Neset Koksal, Bahadir M Gulluoglu, Bulent Unal, Can Atalay, Emin Yıldırım, Ergun Erdem, Semra Salimoglu, Atakan Sezer, Ayhan Koyuncu, Gunay Gurleyik, Haluk Alagol, Nalan Ulufi, Uğur Berberoglu, Mustafa Dulger, Omer Cengiz, Efe Sezgin, Ronald Johnson
BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group...
May 17, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29776911/shorter-trastuzumab-course-still-effective
#14
(no author information available yet)
Reducing the duration of trastuzumab treatment may be beneficial for women with HER2-positive breast cancer: In the phase III PERSEPHONE trial, women who received the drug for 6 months had a similar rate of disease-free survival as women on a 12-month course, but were half as likely to stop treatment due to cardiac side effects.
May 18, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29776344/risk-factors-for-esophageal-fistula-in-thoracic-esophageal-squamous-cell-carcinoma-invading-adjacent-organs-treated-with-definitive-chemoradiotherapy-a-monocentric-case-control-study
#15
Takeshi Kawakami, Takahiro Tsushima, Katsuhiro Omae, Hirofumi Ogawa, Hiromichi Shirasu, Yosuke Kito, Yukio Yoshida, Satoshi Hamauchi, Akiko Todaka, Nozomu Machida, Tomoya Yokota, Kentaro Yamazaki, Akira Fukutomi, Yusuke Onozawa, Hirofumi Yasui
BACKGROUND: Standard treatment for unresectable esophageal squamous cell carcinoma (ESCC) without distant metastasis is definitive chemoradiotherapy (dCRT), in which the incidence of esophageal fistula (EF) is reported to be 10-12%. An ad hoc analysis of JCOG0303, a phase II/III trial of dCRT for patients with unresectable ESCC (including non-T4b), suggested that esophageal stenosis is a risk factor for EF. However, risk factors for EF in patients limited to T4b ESCC treated with dCRT have yet to be clarified...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#16
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#17
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29773991/first-biologic-drug-in-the-treatment-of-ras-wild-type-metastatic-colorectal-cancer-anti-egfr-or-bevacizumab-results-from-a-meta-analysis
#18
REVIEW
Alessandro Ottaiano, Alfonso De Stefano, Monica Capozzi, Anna Nappi, Chiara De Divitiis, Carmela Romano, Lucrezia Silvestro, Antonino Cassata, Rossana Casaretti, Salvatore Tafuto, Michele Caraglia, Massimiliano Berretta, Guglielmo Nasti, Antonio Avallone
Introduction: We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Patients and Methods: Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773080/adjuvant-ny-eso-1-vaccine-immunotherapy-in-high-risk-resected-melanoma-a-retrospective-cohort-analysis
#19
Michael Lattanzi, Joseph Han, Una Moran, Kierstin Utter, Jeremy Tchack, Rachel Lubong Sabado, Russell Berman, Richard Shapiro, Hsin-Hui Huang, Iman Osman, Nina Bhardwaj, Anna C Pavlick
BACKGROUND: Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls. METHODS: All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort...
May 18, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29768118/final-overall-survival-analysis-from-a-study-comparing-first-line-crizotinib-with-chemotherapy-results-from-profile-1014
#20
Benjamin J Solomon, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Yiyun Tang, Keith D Wilner, Fiona Blackhall, Tony S Mok
Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin (area under the concentration-time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171)...
May 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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