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https://www.readbyqxmd.com/read/28735067/treatment-sequence-with-either-irinotecan-cetuximab-followed-by-folfox-4-or-the-reverse-strategy-in-metastatic-colorectal-cancer-patients-progressing-after-first-line-folfiri-bevacizumab-an-italian-group-for-the-study-of-gastrointestinal-cancer-phase-iii-randomised
#1
Stefano Cascinu, Gerardo Rosati, Guglielmo Nasti, Sara Lonardi, Alberto Zaniboni, Paolo Marchetti, Francesco Leone, Domenico Bilancia, Rosario Vincenzo Iaffaioli, Vittorina Zagonel, Monica Giordano, Domenico C Corsi, Francesco Ferraú, Roberto Labianca, Monica Ronzoni, Mario Scartozzi, Francesca Galli
INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B)...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28732369/efficacy-and-safety-of-accelerated-partial-breast-irradiation-a-meta-analysis-of-published-randomized-studies
#2
Gengchun Liu, Zhongyi Dong, Baqun Huang, Yuelong Liu, Yan Tang, Qing Li, Yihui Zhu
BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) technology has theoretical advantages in comparison with traditional adjuvant radiation therapy (whole-breast irradiation; WBI) after breast-conserving surgery. However, published randomized controlled trials have shown inconsistent outcomes. Therefore, a comprehensive assessment of the effectiveness and safety of APBI technology is needed. RESULTS: A total of 7 studies of 7452 patients were included in this analysis...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28724419/real-life-clinical-practice-results-with-vinflunine-in-patients-with-relapsed-platinum-treated-metastatic-urothelial-carcinoma-an-italian-multicenter-study-movie-goirc-01-2014
#3
Rodolfo Passalacqua, Silvia Lazzarelli, Maddalena Donini, Rodolfo Montironi, Rosa Tambaro, Ugo De Giorgi, Sandro Pignata, Raffaella Palumbo, Giovanni Luca Ceresoli, Gianluca Del Conte, Giuseppe Tonini, Franco Morelli, Franco Nolè, Stefano Panni, Ermanno Rondini, Annalisa Guida, Paolo Andrea Zucali, Laura Doni, Elisa Iezzi, Caterina Caminiti
BACKGROUND: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice...
July 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28721753/nintedanib-in-ovarian-cancer
#4
Saira Khalique, Susana Banerjee
Advanced ovarian cancer remains an unmet clinical need. Angiogenesis is considered a therapeutic target in ovarian cancer, with bevacizumab, a monoclonal antibody against VEGF, being the first drug to show a progression-free survival benefit. Nintedanib is an oral tyrosine kinase inhibitor targeting VEGF receptor 1-3, FGFR 1-3 and PDGFR α and β, which has entered phase III trial development in ovarian cancer. Areas covered: This article reviews the preclinical and clinical efficacy of nintedanib in ovarian cancer, its pharmacokinetic and pharmacodynamics profile, safety issues, together with an overview of clinical trials carried out so far...
July 19, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28719890/effect-of-neoadjuvant-nab-paclitaxel-plus-gemcitabine-therapy-on-overall-survival-in-patients-with-borderline-resectable-pancreatic-cancer-a-prospective-multicenter-phase-ii-trial-nac-ga-trial
#5
Ken-Ichi Okada, Toshio Shimokawa, Seiko Hirono, Manabu Kawai, Masayuki Sho, Sohei Satoi, Ippei Matsumoto, Hidetoshi Eguchi, Yoshiaki Murakami, Suguru Yamada, Mariko Doi, Hiroki Yamaue
We conducted a prospective multicenter phase II trial of patients with borderline resectable pancreatic carcinoma to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (OS). The clinical trial primarily evaluated OS time from the first day of protocol therapy as a primary endpoint. The secondary endpoints were recurrence-free survival from the first day of protocol therapy, safety of the protocol therapy (adverse effect), morbidity based on the Clavien Dindo classification of more than III, response rate, preoperative/postoperative tumor marker (CA 19-9, CEA), rate of normalization, reduction rate of the maximum standardized uptake value on positron emission tomography-computed tomography (limited to institutions where positron emission tomography-computed tomography was available), chemotherapeutic effect grade based on Evans' classification, resection rate, R0 resection rate, surgical data (operative time, blood loss, transfusion, postoperative hospital day), overall morbidity rates (reoperation, rate of readmission, mortality), patient rate in postoperative adjuvant therapy (entry rate, completion rate), dose intensity, quality of life regarding fatigue and malaise assessed by the questionnaire of FACIT-F (Japanese version), and peripheral sensory neuropathy assessed by the questionnaire of the FACT/GOG-NTX subscale (version 4; Japanese version)...
July 19, 2017: Oncology
https://www.readbyqxmd.com/read/28716370/a-systematic-review-and-framework-for-the-use-of-hormone-therapy-with-salvage-radiation-therapy-for-recurrent-prostate-cancer
#6
REVIEW
Daniel E Spratt, Robert T Dess, Zachary S Zumsteg, Daniel W Lin, Phuoc T Tran, Todd M Morgan, Emmanuel S Antonarakis, Paul L Nguyen, Charles J Ryan, Howard M Sandler, Matthew R Cooperberg, Edwin Posadas, Felix Y Feng
CONTEXT: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. OBJECTIVE: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. EVIDENCE ACQUISITION: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials...
July 14, 2017: European Urology
https://www.readbyqxmd.com/read/28712615/predicting-real-world-effectiveness-of-cancer-therapies-using-overall-survival-and-progression-free-survival-from-clinical-trials-empirical-evidence-for-the-asco-value-framework
#7
Darius N Lakdawalla, Jason Shafrin, Ningqi Hou, Desi Peneva, Seanna Vine, Jinhee Park, Jie Zhang, Ron Brookmeyer, Robert A Figlin
OBJECTIVES: To measure the relationship between randomized controlled trial (RCT) efficacy and real-world effectiveness for oncology treatments as well as how this relationship varies depending on an RCT's use of surrogate versus overall survival (OS) endpoints. METHODS: We abstracted treatment efficacy measures from 21 phase III RCTs reporting OS and either progression-free survival or time to progression endpoints in breast, colorectal, lung, ovarian, and pancreatic cancers...
July 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#8
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
July 11, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28707844/castration-resistance-prostate-cancer-what-is-in-the-pipeline
#9
Cosimo DE Nunzio, Fabrizio Presicce, Silvana Giacinti, Maria Bassanelli, Andrea Tubaro
INTRODUCTION: To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments. EVIDENCE ACQUISITION: A systematic literature search from from January 2000 until March 2017 was performed by combining the following MESH terms: castrate resistant prostate cancer, abiraterone, enzalutamide, 223radium, sipuleucel-T, docetaxel, cabazitaxel, resistance mechanisms, resistance to androgen deprivation, Androgen Receptor (AR) mutations, amplifications, splice variants, and AR alterations...
July 12, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28707274/cancer-immunotherapies-are-they-as-effective-in-the-elderly
#10
Kate Poropatich, Joel Fontanarosa, Sandeep Samant, Jeffrey A Sosman, Bin Zhang
Almost two-thirds of all new cancer diagnoses are made in persons over the age of 65 years, yet it is unclear if age affects patient responsiveness to immunotherapy, which is increasingly becoming first-line therapy in advanced stages of different tumor types. Preclinical animal studies may be difficult to translate into humans since they frequently use young mice (2-3 months of age) equivalent to adolescent human subjects. Nevertheless, ex vivo studies from humans are concordant with mice tissue findings-older patients have an increased density of circulating regulatory immune cells and a decreased ratio of naïve-to-memory T cells...
July 13, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28705024/medi-4736-durvalumab-in-non-small-cell-lung-cancer
#11
Arnaud Jeanson, Fabrice Barlesi
Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences...
July 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28702772/a-phase-ii-trial-of-erlotinib-monotherapy-in-advanced-pancreatic-cancer-as-a-first-or-second-line-agent
#12
Christos Fountzilas, Ravi Chhatrala, Nikhil Khushalani, Wei Tan, Charles LeVea, Alan Hutson, Chris Tucker, Wen Wee Ma, Graham Warren, Patrick Boland, Renuka Iyer
INTRODUCTION: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. METHODS: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression...
July 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28702409/phase-iib-trial-comparing-two-concurrent-cisplatin-schedules-in-locally-advanced-head-and-neck-cancer
#13
Lekha Madhavan Nair, R Rejnish Kumar, Kainickal Cessal Thomachan, Malu Rafi, Preethi Sara George, K M Jagathnath Krishna, Kunnambath Ramadas
BACKGROUND: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m(2)) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. OBJECTIVES: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m(2)) with weekly cisplatin (40 mg/m(2)) concurrently with radiation in patients with locally advanced head and neck cancer...
April 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28701571/neoadjuvant-therapy-with-weekly-nanoparticle-albumin-bound-paclitaxel-for-luminal-early-breast-cancer-patients-results-from-the-nabrax-study-geicam-2011-02-a-multicenter-non-randomized-phase-ii-trial-with-a-companion-biomarker-analysis
#14
Miguel Martín, José I Chacón, Antonio Antón, Arrate Plazaola, Elena García-Martínez, Miguel A Seguí, Pedro Sánchez-Rovira, José Palacios, Lourdes Calvo, Carmen Esteban, Enrique Espinosa, Agusti Barnadas, Norberto Batista, Angel Guerrero, Montserrat Muñoz, Estefania Romio, César Rodríguez-Martín, Rosalía Caballero, María I Casas, Federico Rojo, Eva Carrasco, Silvia Antolín
BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab-Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) disease. MATERIALS AND METHODS: Women with ER+, HER2-, stage II-III BC were treated preoperatively with four cycles of weekly nab-Paclitaxel (150 mg/m(2)), 3 weeks on and 1 week off...
July 12, 2017: Oncologist
https://www.readbyqxmd.com/read/28700344/decoy-receptor-1-dcr1-promoter-hypermethylation-and-response-to-irinotecan-in-metastatic-colorectal-cancer
#15
Linda J W Bosch, Geert Trooskens, Petur Snaebjornsson, Veerle M H Coupé, Sandra Mongera, Josien C Haan, Susan D Richman, Miriam Koopman, Jolien Tol, Tim de Meyer, Joost Louwagie, Luc Dehaspe, Nicole C T van Grieken, Bauke Ylstra, Henk M W Verheul, Manon van Engeland, Iris D Nagtegaal, James G Herman, Philip Quirke, Matthew T Seymour, Cornelis J A Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A Meijer
Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients.Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI))...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699820/expanded-strain-coverage-for-a-highly-successful-public-health-tool-prophylactic-9-valent-human-papillomavirus-vaccine
#16
Zhigang Zhang, Jun Zhang, Ningshao Xia, Qinjian Zhao
Human papillomavirus is considered the causative factor for cervical cancer, which accounts for approximately 5% of the global cancer burden and more than 600,000 new cases annually that are attributable to HPV infection worldwide. The first-generation prophylactic HPV vaccines, Gardasil® and Cervarix®, were licensed approximately a decade ago. Both vaccines contain the most prevalent high-risk types, HPV16 and 18, which are associated with 70% of cervical cancer. To further increase the type coverage, five additional oncogenic HPV types (31, 33, 45, 52 and 58) were added to the existing Gardasil-4 to develop a 9-valent HPV vaccine (9vHPV), Gardasil 9®, increasing the potential level of protection from ∼70% to ∼90%...
July 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28679776/phase-i-trial-of-intravenous-oncolytic-vaccinia-virus-gl-onc1-with-cisplatin-and-radiotherapy-in-patients-with-locoregionally-advanced-head-and-neck-carcinoma
#17
Loren K Mell, Kevin T Brumund, Gregory A Daniels, Sunil J Advani, Kaveh Zakeri, Mary E Wright, Sara-Jane Onyeama, Robert A Weisman, Parag R Sanghvi, Peter J Martin, Aladar A Szalay
Pre-clinical models have shown that the effectiveness of GL-ONC1, a modified <p>oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study</p> <p>was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy</p> <p>to patients with primary, non-metastatic head and neck cancer.</p> <p>EXPERIMENTAL DESIGN: Patients with locoregionally advanced unresected, non-metastatic</p> <p>carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were</p> <p>treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and</p> <p>chemotherapy...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28676010/kca3-1-channel-modulators-as-potential-therapeutic-compounds-for-glioblastoma
#18
Brandon M Brown, Brandon Pressley, Heike Wulff
The intermediate-conductance Ca2+-activated K+ channel KCa3.1 is widely expressed in cells of the immune system such as T- and B-lymphocytes, mast cells, macrophages and microglia, but also found in dedifferentiated vascular smooth muscle cells, fibroblasts and many cancer cells including pancreatic, prostate, leukemia and glioblastoma. In all these cell types KCa3.1 plays an important role in cellular activation, migration and proliferation by regulating membrane potential and Ca2+ signaling. KCa3.1 therefore constitutes an attractive therapeutic target for diseases involving excessive proliferation or activation of one more of these cell types and researchers both in academia and in the pharmaceutical industry have developed several potent and selective small molecule inhibitors of KCa3...
June 30, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28675836/natural-alkaloids-as-p-gp-inhibitors-for-multidrug-resistance-reversal-in-cancer
#19
REVIEW
Prashant Joshi, Ram A Vishwakarma, Sandip B Bharate
The biggest challenge associated with cancer chemotherapy is the development of cross multi-drug resistance to almost all anti-cancer agents upon chronic treatment. The major contributing factor for this resistance is efflux of the drugs by the p-glycoprotein pump. Over the years, inhibitors of this pump have been discovered to administer them in combination with chemotherapeutic agents. The clinical failure of first and second generation P-gp inhibitors (such as verapamil and cyclosporine analogs) has led to the discovery of third generation potent P-gp inhibitors (tariquidar, zosuquidar, laniquidar)...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28675058/selumetinib-for-the-treatment-of-non-small-cell-lung-cancer
#20
Francesca Casaluce, Assunta Sgambato, Paolo Maione, Paola Claudia Sacco, Giuseppe Santabarbara, Cesare Gridelli
KRAS is the most frequently mutated oncogene in NSCLC, occurring in around a third of patients. However, this largest genomically defined subgroup of lung cancer patients seem to remain "undruggable", with any effective targeted therapy approved at the moment. The prognostic and predictive power and thus the clinical utility of KRAS oncogenic mutations in lung cancer are highly debated issues, not supportive of KRAS testing in clinical practice of NSCLC therapy. Areas covered: A phase II trial in KRAS-mutant NSCLC had shown significant improvements in PFS and ORR in patients treated with selumetinib plus docetaxel compared to docetaxel alone...
July 4, 2017: Expert Opinion on Investigational Drugs
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