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Muhammad W Saif, Melissa Smith, Antonio Maloney
5-Fluorouracil (5-FU) is the backbone of the chemotherapy regimens approved for treatment of many malignancies, especially colorectal cancer (CRC). The incidence of cardiotoxicity associated with 5-FU ranges between 1.5% to 18% and is most commonly manifested as anginal symptoms. Cardiomyopathy is very rarely reported with 5-FU and capecitabine. A 35-year-old Caucasian male with T3, N1, M0 rectal cancer after the initial neoadjuvant chemoradiation with 5FU/LV followed by surgical abdominoperineal resection (APR), began mFOLFOX6 in the adjuvant setting...
September 14, 2016: Curēus
Tetsuhito Muranaka, Satoshi Yuki, Yoshito Komatsu, Kentaro Sawada, Kazuaki Harada, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Naoya Sakamoto
PURPOSE: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. MATERIALS AND METHODS: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital...
September 2016: Journal of Gastric Cancer
Taehwan Park, Chang-Ju Choi, Yeera Choi, Dong-Churl Suh
Cetuximab is a novel biological agent with superior therapeutic efficacy for colorectal cancer treatment. This study aimed to systematically review the existing evidence related to the cost-effectiveness of cetuximab. Areas covered: Using Medline and Cochrane Database of Systematic Reviews, a total of 12 articles were identified. Previous studies have shown mixed results on the cost-effectiveness of first-line cetuximab combined with FOLFIRI (5-Fluorouracil, leucovorin, irinotecan). However, cetuximab-irinotecan therapy as third-line treatment has consistently been found to be cost-ineffective compared to best supportive care or no third-line therapy...
October 18, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
Min-Jeong Kim, Eun Seok Kim, Seung-Gu Yeo
BACKGROUND: Standard management for locally advanced rectal cancer (LARC) involves preoperative chemoradiotherapy (CRT) and radical surgery. However, this level of treatment may be unnecessary for a subgroup of LARC patients. Previous reports have shown that approximately 20% of LARC patients experience a complete tumor response to preoperative CRT. Post-CRT nonoperative management of these patients may prevent morbidities associated with radical surgery. To our knowledge, this case report firstly presents the favorable long-term outcomes of a LARC patient who underwent definitive aim CRT...
October 2016: Medicine (Baltimore)
Fausto Petrelli, Gianluca Tomasello, Michele Ghidini, Rodolfo Passalacqua, Sandro Barni
Combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) is an active but not well-tolerated regimen for advanced gastric cancer (GC) with standard 3-weekly doses. Several modified schedules (mDCFs) have been designed to reduce acute toxicities and improve feasibility as first-line therapy in patients with metastatic GC. The objective of this systematic review was to evaluate overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade (G) greater than or equal to 3 adverse event of mDCF chemotherapy in this setting...
September 30, 2016: Anti-cancer Drugs
Shuitu Feng, Zhigao Zheng, Lihua Feng, Lihong Yang, Zuhong Chen, Yubiao Lin, Yingqin Gao, Yide Chen
The cancer stem cell (CSC) model suggests that a small subset of cancer cells possess stem cell properties and plays a crucial role in tumor initiation, metastasis and resistance to anticancer therapy. Exploration of the specific therapies targeting at CSCs has been a crucial issue in antitumor research. Gastric cancer (GC) cells often exist in an ischemic microenvironment with acidic conditions in vivo, thus maintenance of cellular pH homeostasis is important for the survival and function of GC cells. Proton pump inhibitors (PPIs) may prevent intracellular proton extrusions which consequently reduce cancer cell survival under acidic conditions...
October 7, 2016: Oncology Reports
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
October 6, 2016: Molecular Medicine Reports
James J Farrell, Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine...
November 2016: Pancreas
Markovic Srdjan, Antic Jadranka, Dimitrijevic Ivan, Zogovic Branimir, Bojic Daniela, Svorcan Petar, Markovic Velimir, Krivokapic Zoran
BACKGROUND & OBJECTIVES: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. METHODS: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009)...
May 2016: Indian Journal of Medical Research
Rohan C Parikh, Xianglin L Du, Robert O Morgan, David R Lairson
BACKGROUND: Over the last decade, multiple chemotherapies/targeted biologics have been approved for metastatic colorectal cancer (mCRC). However, evidence is limited with regards to the array of treatments received by mCRC patients. OBJECTIVE: This study examines treatment sequences (first- to third-line chemotherapy/targeted biologics) and the factors associated with first-line targeted biologics and common treatment sequences for elderly mCRC patients treated in a community setting...
March 2016: Drugs—Real World Outcomes
Sadamoto Zenda, Takashi Kojima, Ken Kato, Sachiko Izumi, Taijiro Ozawa, Naomi Kiyota, Chikatoshi Katada, Takahiro Tsushima, Yoshinori Ito, Tetsuo Akimoto, Yasuhisa Hasegawa, Miyuki Kanamaru, Hiroyuki Daiko
PURPOSE: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer. PATIENTS AND METHODS: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP)...
September 3, 2016: International Journal of Radiation Oncology, Biology, Physics
Rebecca B Goody, Helen MacKay, Bethany Pitcher, Amit Oza, Lillian L Siu, John Kim, Rebecca K S Wong, Eric Chen, Carol Swallow, Jennifer Knox, Zahra Kassam, Bernard Cummings, Ron Feld, David Hedley, Geoffrey Liu, Monika K Krzyzanowska, Robert Dinniwell, Anthony M Brade, Laura A Dawson, Melania Pintilie, Jolie Ringash
PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma...
August 31, 2016: International Journal of Radiation Oncology, Biology, Physics
Feng-Hua Wang, Yun Wang, Zhen-Dong Chen, Jian-Hua Chen, Feng-Zhan Qin, Wen-Qi Jiang, Yu-Hong Li
Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m(2)/d and 20 µg/m(2)/d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m(2)/d rhLTα-Da followed by DDP (15 mg/m(2)/d) and 5-Fu (750 mg/m(2)/d) on days 1-5...
November 2016: Medical Oncology
Georgia Sioupouli, George Lambrinidis, Emmanuel Mikros, Sotiris Amillis, George Diallinas
NCS1 proteins are H(+) or Na(+) symporters responsible for the uptake of purines, pyrimidines or related metabolites in bacteria, fungi and some plants. Fungal NCS1 are classified into two evolutionary and structurally distinct subfamilies, known as Fur- and Fcy-like transporters. These subfamilies have expanded and functionally diversified by gene duplications. The Fur subfamily of the model fungus Aspergillus nidulans includes both major and cryptic transporters specific for uracil, 5-fluorouracil, allantoin or/and uric acid...
October 14, 2016: Molecular Microbiology
Magdalene A Dohil
BACKGROUND: Actinic keratosis (AK) is a neoplastic keratosis and a precursor of squamous cell carcinoma (SCC). OBJECTIVE: We are presenting data on a novel formulation of 4% 5-Fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil (Tolak) with once daily application versus treatment with 5% 5-FU twice daily for 4 weeks. METHODS: 1) A dose ranging study of 4% 5-FU cream once or twice daily for 2 or 4 weeks and its vehicle, compared to 5% 5-FU cream twice daily for 4 weeks in 121 subjects...
October 1, 2016: Journal of Drugs in Dermatology: JDD
Elfriede Bollschweiler, Arnulf H Hölscher, Till Herbold, Ralf Metzger, Hakan Alakus, Henner Schmidt, Uta Drebber, Ute Warnecke-Eberz
OBJECTIVE: The aim of this study was to evaluate the predictive value of a single or combination of biomarker(s) for histopathologic non-response to neoadjuvant chemoradiation in esophageal cancer. SUMMARY OF BACKGROUND DATA: Patients without response to neoadjuvant chemoradiation for esophageal cancer have no prognostic benefits, but experience time delays and risk side effects. METHODS: Inclusion criteria for this prospective diagnostic study were patients with cT3,Nx,M0, esophageal squamous cell or adenocarcinoma and planned neoadjuvant chemoradiation (5- fluorouracil, cisplatin, 40Gy) followed by 2-field transthoracic esophagectomy...
November 2016: Annals of Surgery
Chintan A Dalwadi, Gayatri C Patel
BACKGROUND: The objective of the study was to investigate the cytotoxicity and cellular uptake of prepared 5-Fluorouracil (5-FU) nanohydrogel formulation using KB oral cancer cell line and VERO fibroblast cell line. METHOD: The biodegradable thermoresponsive modified methylcellulose (MMC) polymer was used for the preparation of nanohydrogel whereas it shows sol-gel phase transition at 36˚C to 40˚C. The physical crosslinking method was used followed by probe sonication for the preparation of 5-FU loaded MMC nanohydrogel...
October 13, 2016: Current Drug Delivery
Marina Borro, Andrea Botticelli, Federica Mazzuca, Elisa Concetta Onesti, Giovanna Gentile, Adriana Romiti, Bruna Cerbelli, Eva Mazzotti, Luca Marchetti, Luana Lionetto, Maurizio Simmaco, Paolo Marchetti
BACKGROUND: 5-fluorouracil (5-FU) based chemotherapy is the most common first line regimen used in gastric and gastroesophageal junction cancer, but development of severe toxicity is a main concern in the treatment. The present study is aimed to evaluate a novel pre-treatment assay, known as the 5-FU degradation rate (5-FUDR), as a predictive factor for 5-FU toxicity. METHODS: Pre-treatment 5-FUDR and gene polymorphisms related to 5-FU metabolism (DPYDIVS14+1G>A, MTHFRA1298T or C677T, TMYS TSER) were characterized in gastro-esophageal cancer patients...
October 11, 2016: Oncotarget
Hyun Ju Kim, Yang-Gun Suh, Yong Chan Lee, Sang Kil Lee, Sung Kwan Shin, Byung Chul Cho, Chang Geol Lee
Purpose: The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Materials and Methods: Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of <60 Gy (standard-dose group), while 116 received ≥60 Gy (high-dose group)...
October 6, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Cheng Wen Yao, Kyoung Ah Kang, Mei Jing Piao, Yea Seong Ryu, Pattage Madushan Dilhara Jayatissa Fernando, Min Chang Oh, Jeong Eon Park, Kristina Shilnikova, Soo-Young Na, Seung Uk Jeong, Sun-Jin Boo, Jin Won Hyun
We investigated the role of autophagy in SNUC5/5-FUR, 5-fluorouracil (5-FU) resistant SNUC5 colon cancer cells. SNUC5/5-FUR cells exhibited low level of autophagy, as determined by light microscopy, confocal microscopy, and flow cytometry following acridine orange staining, and the decreased level of GFP-LC3 puncta. In addition, expression of critical autophagic proteins such as Atg5, Beclin-1 and LC3-II and autophagic flux was diminished in SNUC5/5-FUR cells. Whereas production of reactive oxygen species (ROS) was significantly elevated in SNUC5/5-FUR cells, treatment with the ROS inhibitor N-acetyl cysteine further reduced the level of autophagy...
October 17, 2016: Biomolecules & Therapeutics
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