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https://www.readbyqxmd.com/read/29346040/bevacizumab-maintenance-versus-no-maintenance-during-chemotherapy-free-intervals-in-metastatic-colorectal-cancer-a-randomized-phase-iii-trial-prodige-9
#1
Thomas Aparicio, Francois Ghiringhelli, Valérie Boige, Karine Le Malicot, Julien Taieb, Olivier Bouché, Jean-Marc Phelip, Eric François, Christian Borel, Roger Faroux, Laetitia Dahan, Stéphane Jacquot, Dominique Genet, Faiza Khemissa, Etienne Suc, Françoise Desseigne, Patrick Texereau, Come Lepage, Jaafar Bennouna
Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI...
January 18, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29344244/identification-and-validation-of-psat1-as-a-potential-prognostic-factor-for-predicting-clinical-outcomes-in-patients-with-colorectal-carcinoma
#2
Cheng Qian, Yongsheng Xia, Yun Ren, Yan Yin, Anmei Deng
The aim of the present study was to explore the existence of known or candidate drug-target genes that are upregulated in colorectal cancer (CRC) and may serve as novel prognostic factors or therapeutic targets for this type of malignancy. An in silico analysis was conducted using the Oncomine tool to compare the expression levels of a list of drug-target genes between cancerous and normal tissues in 6 independent CRC cohorts retrieved from the Oncomine database. Phosphoserine aminotransferase 1 (PSAT1) was identified as the top-ranked upregulated gene in CRC tumors, and was highly expressed in patients with chemoresistant disease...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29340601/how-to-treat-borderline-resectable-pancreatic-cancer-current-challenges-and-future-directions
#3
Shinichiro Takahashi
Borderline resectable pancreatic cancer (BRPC) is an advanced tumor in contact with the surrounding major vessels, making R0 resection difficult to achieve. Neoadjuvant treatment is expected to provide substantial local control and prolong survival. However, there is no standard treatment. I therefore conducted a strategic literature search from January 2013 to September 2017 and identified 37 clinical studies of pancreatic cancer, including BRPC, to evaluate treatment interventions. Twenty (54%) studies were prospective...
January 11, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29340058/a-multicenter-prospective-phase-ii-study-of-first-line-modified-folfirinox-for-unresectable-advanced-pancreatic-cancer
#4
Kensaku Yoshida, Takuji Iwashita, Shinya Uemura, Akinori Maruta, Mitsuru Okuno, Nobuhiro Ando, Keisuke Iwata, Junji Kawaguchi, Tsuyoshi Mukai, Masahito Shimizu
Background: FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance. Aims: To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340025/the-novel-atm-inhibitor-az31-enhances-antitumor-activity-in-patient-derived-xenografts-that-are-resistant-to-irinotecan-monotherapy
#5
Justin Greene, Anna Nguyen, Stacey M Bagby, Gemma N Jones, W M Tai, Kevin S Quackenbush, Anna Schreiber, Wells A Messersmith, Kalpana M Devaraj, Patrick Blatchford, S Gail Eckhardt, Elaine B Cadogan, Gareth D Hughes, Aaron Smith, Todd M Pitts, John J Arcaroli
Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by generating double strand breaks resulting in DNA damage. The activation of the ATM pathway plays a fundamental role in regulating the cellular response and repair to DNA damage. The objective of this preclinical study was to determine whether ATM inhibition would enhance sensitivity to irinotecan treatment. Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in CRC cell lines and CRC patient derived xenografts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334603/multicenter-phase-ii-study-of-oxaliplatin-irinotecan-and-s-1-as-first-line-treatment-for-patients-with-recurrent-or-metastatic-biliary-tract-cancer
#6
Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-Pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang
Purpose: Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. Materials and Methods: Chemotherapy-naive patients with histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study...
January 8, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29332390/high-drug-loading-and-sub-quantitative-loading-efficiency-of-polymeric-micelles-driven-by-donor-receptor-coordination-interactions
#7
Shixian Lv, Yuchen Wu, Kaimin Cai, Hua He, Yongjuan Li, Min Lan, Xuesi Chen, Jianjun Cheng, Lichen Yin
Polymeric micelles are extensively used for the delivery of hydrophobic drugs, which however, suffer from unsatisfactory drug loading, colloidal uniformity, formulation stability, and drug release. Herein, we demonstrate a convenient strategy to prepare micelles with ultra-high drug loading via the incorporation of polymer-drug coordination interactions. An amphiphilic copolymer containing pendant phenylboronic acid as electron acceptor unit was synthesized, which afforded donor-acceptor coordination with doxorubicin to obtain micelles with ultra-high drug loading (~50%), nearly quantitative loading efficiency (>95%), uniform size, and colloidal stability...
January 13, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29330749/toxicity-and-efficacy-of-lomustine-and-bevacizumab-in-recurrent-glioblastoma-patients
#8
J N Jakobsen, T Urup, K Grunnet, A Toft, M D Johansen, S H Poulsen, I J Christensen, A Muhic, H S Poulsen
The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330005/a-phase-i-study-of-irinotecan-capecitabine-xeloda-and-oxaliplatin-in-patients-with-advanced-colorectal-cancer
#9
Jean Maroun, Horia Marginean, Derek Jonker, Christine Cripps, Rakesh Goel, Timothy Asmis, Rachel Goodwin, Gabriela Chiritescu
BACKGROUND: The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients received oxaliplatin followed by irinotecan as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID) on days 2 to 15 of a 3-week cycle...
December 15, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29328485/knockdown-of-hnrnp-a2-b1-inhibits-cell-proliferation-invasion-and-cell-cycle-triggering-apoptosis-in-cervical-cancer-via-pi3k-akt-signaling-pathway
#10
Xiang Shi, Li Ran, Yao Liu, Shu-Huai Zhong, Ping-Ping Zhou, Ming-Xin Liao, Wen Fang
Cervical cancer is currently one of the major threats to women's health. The overexpression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as the biomarker has been investigated in various cancers. In our previous study, we found that lobaplatin induced apoptosis and cell cycle arrest via downregulation of proteins including hnRNP A2/B1 in cervical cancer cells. However, the underlying relationship between hnRNP A2/B1 and cervical cancer remained largely unknown. hnRNP A2/B1 knock‑down in HeLa and CaSki cells was performed by shRNA transfection...
January 5, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29324814/comprehensive-molecular-profiling-of-advanced-metastatic-olfactory-neuroblastomas
#11
Jasmina Topcagic, Rebecca Feldman, Anatole Ghazalpour, Jeffrey Swensen, Zoran Gatalica, Semir Vranic
Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry...
2018: PloS One
https://www.readbyqxmd.com/read/29322928/constraint-based-perturbation-analysis-with-cluster-newton-method-a-case-study-of-personalized-parameter-estimations-with-irinotecan-whole-body-physiologically-based-pharmacokinetic-model
#12
Shun Asami, Daisuke Kiga, Akihiko Konagaya
BACKGROUND: Drug development considering individual varieties among patients becomes crucial to improve clinical development success rates and save healthcare costs. As a useful tool to predict individual phenomena and correlations among drug characteristics and individual varieties, recently, whole-body physiologically based pharmacokinetic (WB- PBPK) models are getting more attention. WB-PBPK models generally have a lot of drug-related parameters that need to be estimated, and the estimations are difficult because the observed data are limited...
December 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29316651/cpt-11-induced-delayed-diarrhea-develops-via-reduced-aquaporin-3-expression-in-the-colon
#13
Risako Kon, Yuika Tsubota, Moe Minami, Saki Kato, Yukari Matsunaga, Hiroshi Kimura, Yuta Murakami, Tetsuya Fujikawa, Ryoya Sakurai, Rei Tomimoto, Yoshiaki Machida, Nobutomo Ikarashi, Kiyoshi Sugiyama
While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29307857/role-of-regulatory-t-cells-in-irinotecan-induced-intestinal-mucositis
#14
Camila Fernandes, Carlos Wagner Souza Wanderley, Camila Meireles Souza Silva, Heitor Amorim Muniz, Maraiza Alves Teixeira, Nathália Ribeiro Pinho Souza, André George Ferreira Cândido, Renata Brito Falcão, Marcellus Henrique Loiola Ponte Souza, Paulo Roberto Carvalho Almeida, Lilia Maria Carneiro Câmara, Roberto César Pereira Lima-Júnior
Intestinal mucositis (IM) is a common side effect of irinotecan-based chemotherapy. The involvement of inflammatory mediators, such as TNF-α, IL1-β, IL-18 and IL-33, has been demonstrated. However, the role of adaptive immune system cells, whose activation is partially regulated by these cytokines, is yet unknown. Thus, we investigated the role of regulatory T cells (Tregs) in irinotecan-induced IM. C57BL/6 mice were injected with saline or irinotecan (75mgkg-1, i.p.), once a day for 4days, and euthanized at day 1, 3, 5 or 7 following the first dose of irinotecan...
January 4, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29305209/survival-benefit-of-palliative-local-treatments-and-efficacy-of-different-pharmacotherapies-in-colorectal-cancer-with-lung-metastasis-results-from-a-large-retrospective-study
#15
Zhenghang Wang, Xicheng Wang, Jiajia Yuan, Xiaotian Zhang, Jun Zhou, Ming Lu, Dan Liu, Jian Li, Lin Shen
BACKGROUND: For most colorectal cancer patients with initial lung metastasis (LM), the only suitable treatments are palliative, including palliative local therapy and pharmacotherapy. We investigated the role of palliative local treatments in prolonging survival and the efficacy of different pharmacotherapies. PATIENTS AND METHODS: After performing a medical record review of 2233 patients with metastatic colorectal cancer, 684 were identified as having LM. Their clinicopathologic characteristics, treatment patterns, and outcomes were analyzed retrospectively...
December 13, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29299355/pilot-trial-of-crlx101-in-patients-with-advanced-chemotherapy-refractory-gastroesophageal-cancer
#16
Joseph Chao, James Lin, Paul Frankel, Andrew J Clark, Devin T Wiley, Edward Garmey, Marwan Fakih, Dean Lim, Vincent Chung, Eloise Luevanos, Scott Eliasof, Mark E Davis, Yun Yen
Background: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer...
December 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29299351/a-phase-2-trial-of-personalized-cytotoxic-therapy-based-on-tumor-immunohistochemistry-in-previously-treated-metastatic-pancreatic-cancer-patients
#17
Ramesh K Ramanathan, Glen J Weiss, Richard G Posner, N V Rajeshkumar, Gayle Jameson, Meraj Aziz, Antje Hoering, Vanessa Bolejack, Anirban Maitra, Monica Fulk, Edward C Stites, William S Hlavacek, Zoran Gatalica, Joanne Xiu, Manuel Hidalgo, Daniel D Von Hoff, Michael T Barrett
Background: The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Methods: Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC...
December 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29297902/-la-combinazione-di-gemcitabina-e-oxaliplatino-gemox-nel-trattamento-del-carcinoma-pancreatico-in-fase-avanzata-di-malattia-le-notizie-sulla-mia-morte-sono-state-esagerate
#18
Jacopo Giuliani, Andrea Bonetti
Riassunto. L'analisi è stata condotta al fine di valutare l'effetto sia sulla sopravvivenza globale (OS) sia sulla sopravvivenza libera da progressione di malattia (PFS) della chemioterapia di combinazione in prima linea per il carcinoma pancreatico in fase avanzata di malattia. La presente analisi è limitata agli studi randomizzati controllati (RCT) di fase III. Successivamente è stata applicata la European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) agli RCT di fase III analizzati per ricavare uno score relativo all'entità del beneficio clinico ottenuto per ciascun RCT...
December 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29288613/the-effect-of-iloprost-in-the-healing-of-colonic-anastomosis-in-rats-under-chemotherapy-with-irinotecan
#19
Stergios Arapoglou, Apostolos Kambaroudis, Ioannis Grivas, Georgios A Delis, Christos Karkos, Konstantinos Ballas, Georgios Zacharioudakis, Panagiotis Petras, Michael Aftzoglou, Ioannis Gouziotis, Georgios Koliakos, Maria Karakwta, Georgios Hahalis
PURPOSE: We have investigated the possible positive effect of iloprost in the healing of colonic anastomosis, in rats under intraperitoneal chemotherapy with irinotecan. METHOD: Forty male Wistar rats have been divided into four groups. They underwent a partial colectomy and a termino-terminal anastomosis. They were administered, intraperitoneally, saline (group 1), irinotecan (group 2), iloprost (group 3), or irinotecan and iloprost (Group 4). After the sacrifice of the animals what followed was an autopsy, a macroscopic examination and the measurement of the anastomotic rupture pressure...
November 2017: Chirurgia
https://www.readbyqxmd.com/read/29285894/the-effect-of-a-single-injection-of-irinotecan-on-the-development-of-enamel-in-the-wistar-rats
#20
Sali Al-Ansari, Rozita Jalali, Ton Bronckers, Judith Raber-Durlacher, Richard Logan, Jan de Lange, Frederik Rozema
Cancer is the second most frequent cause of death in children. Because the prognosis for childhood malignancies has improved, attention has now focused on long-term consequences of cancer treatment. The immediate effects of chemotherapy on soft tissues have been well described; however, there is less information about long-term effects of chemotherapy on the development of dental tissues. To test the association between the effect of chemotherapy on enamel development, we examined two groups of rats: one that had received an intraperitoneal dose of 200 mg/kg of irinotecan, whereas the other (control) group had received vehicle only...
December 28, 2017: Journal of Cellular and Molecular Medicine
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