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Jianjun Peng, Chao Dong, Chang Wang, Weihua Li, Hao Yu, Min Zhang, Qun Zhao, Bo Zhu, Jun Zhang, Wenliang Li, Fenghua Wang, Qiong Wu, Wenhao Zhou, Ying Yuan, Meng Qiu, Gong Chen
BACKGROUND: 5-Fluorouracil (5-FU) and capecitabine-associated cardiotoxicity ranging from asymptomatic electrocardiography (ECG) abnormalities to severe myocardial infarction has been reported in a number of studies, but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date. In the present study, we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU- and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China...
May 11, 2018: Cancer communications
Wakako Yano, Tatsushi Yokogawa, Takeshi Wakasa, Keisuke Yamamura, Akio Fujioka, Kunihiro Yoshisue, Eiji Matsushima, Seiji Miyahara, Hitoshi Miyakoshi, Junko Taguchi, Khoon Tee Chong, Yayoi Takao, Masayoshi Fukuoka, Kenichi Matsuo
5-Fluorouracil (5-FU) is an antimetabolite and exerts antitumor activity via intracellularly and physiologically complicated metabolic pathways. In this study, we designed a novel small molecule inhibitor, TAS-114, which targets the intercellular metabolism of 5-FU to enhance antitumor activity and modulates catabolic pathway to improve the systemic availability of 5-FU. TAS-114 strongly and competitively inhibited deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase), a gatekeeper protein preventing aberrant base incorporation into DNA, and enhanced the cytotoxicity of fluoropyrimidines in cancer cells; however, it had little intrinsic activity...
May 10, 2018: Molecular Cancer Therapeutics
Wen-Yi Zhang, Xing-Xing Chen, Wen-Hao Chen, Hui Zhang, Chang-Lin Zou
Background: The aim of this study was to identify if blood routine parameters and serum tumor marker are potential predictive factors for tumor response to preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer. Materials and Methods: 55 locally advanced rectal cancer patients were treated with preoperative CRT in this study. The total dose of preoperative radiotherapy was 45 Gy in 25 fractions of 1.8 in 5 weeks. All patients concurrently received 825 mg/m2 capecitabine orally twice daily on days 1 to 14 and 22 to 35...
2018: Gastroenterology Research and Practice
Shunsuke Kato, Hiroo Imai, Makio Gamoh, Takenori Takahata, Hisatsugu Ohori, Katsuhiro Yasuda, Tomohito Niitani, Yasuko Murakawa, Kenji Amagai, Hideki Isobe, Yoshiaki Shindo, Michio Kuroki, Yasuhiro Sakamoto, Hideki Shimodaira, Takashi Yoshioka, Chikashi Ishioka
Oxaliplatin-based chemotherapy is a well-established regimen for patients with inoperable and metastatic colorectal cancer. However, one of the major limitations of oxaliplatin-based chemotherapy is sensory neuropathy. It was previously reported that introduction of intermittent oxaliplatin treatment to an oxaliplatin-based regimen has a significant benefit on efficacy or safety. Here, we prospectively assessed whether efficacy and safety of first-line chemotherapy for advanced colorectal cancer are achieved by introduction of withdrawal of oxaliplatin treatment for a certain period (intermittent oxaliplatin treatment)...
2018: Tohoku Journal of Experimental Medicine
Rebecca Wellmann, Brittany A Borden, Keith Danahey, Rita Nanda, Blase N Polite, Walter M Stadler, Mark J Ratain, Peter H O'Donnell
BACKGROUND: Germline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities. METHODS: In total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5. Studies were assessed for design and genotyping quality, clinically relevant outcomes, statistical rigor, and evidence of drug-gene effects...
May 9, 2018: Cancer
Daniel Breadner, Mark David Vincent, Derek Jonker, Christine Cripps, Paul Klimo, James Biagi, Wendy Lam, Anne O'Connell, Frances Whiston, Larry Stitt, Stephen Welch
OBJECTIVES: Palliative chemotherapy's role is to prolong survival while minimizing treatment toxicities to preserve or improve quality of life. We have recently published a phase II trial of dose reduced capecitabine in older or frail patients with advanced colorectal cancer (aCRC). We herein provide a robust analysis of the health related quality of life (HRQoL) data from our trial. METHODS: A single arm multi-centered phase II trial of dose reduced capecitabine (1500 or 2000 mg/m2  days one-fourteen q21 days) in older or frail patients...
May 1, 2018: Journal of Geriatric Oncology
Yoon Young Choi, Hyunki Kim, Su-Jin Shin, Ha Yan Kim, Jinae Lee, Han-Kwang Yang, Woo Ho Kim, Young-Woo Kim, Myeong-Cherl Kook, Young Kyu Park, Hyung-Ho Kim, Hye Seung Lee, Kyung Hee Lee, Mi Jin Gu, Seung Ho Choi, SoonWon Hong, Jong Won Kim, Woo Jin Hyung, Sung Hoon Noh, Jae-Ho Cheong
OBJECTIVE: We investigated microsatellite instability (MSI) status and programed cell death ligand 1 (PD-L1) expression as predictors of prognosis and responsiveness to chemotherapy for stage II/III gastric cancer. BACKGROUND: The clinical implications of MSI status and PD-L1 expression in gastric cancer have not been well-elucidated. METHODS: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial-a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy...
May 1, 2018: Annals of Surgery
(no author information available yet)
No abstract text is available yet for this article.
June 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Finn Ole Larsen, Anne Birgitte Christiansen, Anette Rishøj, Knud Mejer Nelausen, Dorte L Nielsen
INTRODUCTION: The purpose of this study was to evaluate the safety and feasibility of home-based chemotherapy and to compare chemotherapy given at home with chemotherapy given as an outpatient treatment in relation to toxicity, quality of life and patient's preference. METHODS: Patients who had undergone radical surgery for colon cancer and who were eligible to receive adjuvant treatment with capecitabine and oxaliplatin could be included. To ensure patient safety, the first infusion was given at an outpatient clinic...
May 2018: Danish Medical Journal
Arthur Lui, Karen Mulder, Christine Brezden-Masley, Michael Vickers, Jose Monzon, Hagen Kennecke, Rakesh Goel, Larissa Vos, Sunita Ghosh, Horia Marginean, Anthony Fields, Jean Maroun, Jennifer Spratlin
Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m2 & I-160 mg/m2 IV, Day 2-15 X-1900 mg/m2 /day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m2 & I-120 mg/m2 IV, Day 2-15 X-1425 mg/m2 /day PO divided doses)...
May 4, 2018: Investigational New Drugs
Vincenzo Formica, Michaela Benassi, Giovanna Del Vecchio Blanco, Elena Doldo, Laura Martano, Ilaria Portarena, Antonella Nardecchia, Jessica Lucchetti, Cristina Morelli, Emilia Giudice, Piero Rossi, Alessandro Anselmo, Pierpaolo Sileri, Giuseppe Sica, Augusto Orlandi, Riccardo Santoni, Mario Roselli
A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR)...
May 2, 2018: Medical Oncology
Jinghua Tang, Xiaojun Wu, Yanfang Bai, Yuanhong Gao, Wu Jiang, Lingheng Kong, Junzhong Lin, Desen Wan, Zhizhong Pan, Peirong Ding
Purpose: This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC). Methods: From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery...
2018: Journal of Cancer
Matthew Traylor, Jemma L Walker, Adele A Corrigan, Monica A Hernandez, Stephen J Newhouse, Amos A Folarin, Hamel Patel, Paul J Ross, Jeremy D Sanderson, James Spicer, Natalie J Prescott, Christopher G Mathew, Anthony M Marinaki, Cathryn M Lewis
Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers-either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions. Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer...
2018: PloS One
Gemma Bruera, Mario Di Staso, Pierluigi Bonfili, Antonio Galvano, Rosa Manetta, Gino Coletti, Roberto Vicentini, Stefano Guadagni, Corrado Ficorella, Ernesto Di Cesare, Antonio Russo, Enrico Ricevuto
Introduction: Proper administration timing, dose-intensity, efficacy/toxicity ratio of oxaliplatin added to fluoropyrimidin should be improved to safely perform two-drugs intensive preoperative chemoradiotherapy in locally advanced rectal cancer (LARC). This dose-finding study investigated recommended oxaliplatin dose, safety of oxaliplatin/capecitabine regimen and preliminary activity. Methods: Schedule: oxaliplatin dose-levels, 35-40 mg/m2 /week; capecitabine 825 mg/m2 / twice daily, radiotherapy on rectum/nodes, 50/45 Gy, 45 and 9 boost/45 Gy, in first 5 and subsequent patients, 5 days/week, respectively; for 5 weeks...
April 3, 2018: Oncotarget
Toshiki Iwai, Yui Harada, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Yoshikazu Yonemitsu
The anti-VEGF humanized antibody bevacizumab suppresses various malignancies, but tumors can acquire drug resistance. Preclinical studies suggest myeloid-derived suppressor cells (MDSCs) may be associated with tumor refractoriness to anti-VEGF treatment. Here we report a novel mechanism of tumor escape from anti-VEGF therapy. Anti-VEGF treatment enhanced intratumoral recruitment of CD11bhigh /Gr-1high polymorphonuclear (PMN)-MDSCs in anti-VEGF-resistant Lewis lung carcinoma tumors. This effect was diminished by the anticancer agent capecitabine, a pro-drug converted to 5-fluorouracil, but not by 5-fluorouracil itself...
April 3, 2018: Oncotarget
Mansi Upadhyay, Sandeep Kumar Reddy Adena, Harsh Vardhan, Sarita K Yadav, Brahmeshwar Mishra
The research aims the development and optimization of capecitabine loaded interpenetrating polymeric network by ionotropic gelation method using polymers locust bean gum and sodium alginate by QbD approach. FMEA was performed to recognize the risks influencing CQAs. BBD was applied to study the effect of factors (polymer ratio, amount of cross-linker and curing time) on responses (particle size, % drug entrapment and % drug release). Polynomial equations and 3-D graphs were plotted to relate between factors and responses...
April 27, 2018: International Journal of Biological Macromolecules
Toshimi Takano, Junji Tsurutani, Masato Takahashi, Takeharu Yamanaka, Kazuko Sakai, Yoshinori Ito, Junya Fukuoka, Hideharu Kimura, Hidetaka Kawabata, Kenji Tamura, Koji Matsumoto, Kenjiro Aogi, Kazuhiko Sato, Kazuto Nishio, Kazuhiko Nakagawa, Toshiaki Saeki
BACKGROUND: For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. PATIENTS AND METHODS: Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX)...
April 23, 2018: Breast: Official Journal of the European Society of Mastology
Keun-Wook Lee, Dae Young Zang, Min-Hee Ryu, Ki Hyang Kim, Mi-Jung Kim, Hye Sook Han, Sung Ae Koh, Jin Hyun Park, Jin Won Kim, Byung-Ho Nam, In Sil Choi
Introduction: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy...
December 2017: Contemporary Clinical Trials Communications
E C Radu, A I Saizu, R R Grigorescu, A E Croitoru, C Gheorghe
Rationale. Pancreatic neuroendocrine tumors (NETs) are rare neoplasms that develop from the endocrine tissues of the pancreas. They have a better overall prognosis than pancreatic adenocarcinoma. However, all commonly used classification systems reflect a separation between more indolent, well-differentiated tumors and far more aggressive poorly differentiated types that behave clinically more like small-cell carcinoma of the lung. Objective. To present the case of a 62-year-old man with an aggressive pancreatic NET, with liver, splenic and bone metastases who underwent multidisciplinary treatment including several lines of chemotherapy, somatostatin analogs and radiotherapy...
January 2018: Journal of Medicine and Life
Heling Zhang, Guoshuang Shen, Shuisheng Zhang, Feng Du, Yang Cao, Jun Jiang, Fangchao Zheng, Xinfu Ma, Ziyi Wang, Dengfen Ren, Raees Ahmad, Fuxin Zhao, Jiuda Zhao
Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment. Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects...
April 25, 2018: Expert Opinion on Pharmacotherapy
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