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Oral Irinotecan

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https://www.readbyqxmd.com/read/28510802/phase-i-ii-study-of-bi-weekly-xeliri-plus-bevacizumab-treatment-in-patients-with-metastatic-colorectal-cancer-resistant-to-oxaliplatin-based-first-line-chemotherapy
#1
Tsunekazu Mizushima, Mutsumi Fukunaga, Toshinori Sueda, Masataka Ikeda, Takeshi Kato, Ho Min Kim, Toshihiro Kudo, Kohei Murata, Junichi Nishimura, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
PURPOSE: We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. METHODS: Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm(2) and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2-8...
May 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28454122/olaparib-in-combination-with-irinotecan-cisplatin-and-mitomycin-c-in-patients-with-advanced-pancreatic-cancer
#2
Mark Yarchoan, Melinda C Myzak, Burles A Johnson Iii, Ana De Jesus-Acosta, Dung T Le, Elizabeth M Jaffee, Nilofer S Azad, Ross C Donehower, Lei Zheng, Paul E Oberstein, Robert L Fine, Daniel A Laheru, Michael Goggins
BACKGROUND: Olaparib is an oral inhibitor of polyadenosine 5'-diphosphoribose polymerization (PARP) that has previously shown signs of activity in patients with BRCA mutations and pancreatic ductal adenocarcinoma (PDAC). RESULTS: 18 patients with unresectable PDAC were enrolled. The MTD of olaparib plus IC was olaparib 100 mg twice-daily on days 1 and 8. The addition of mitomycin C to this dose level was not tolerated. Grade ≥3 drug-related adverse events (AEs) were encountered in 16 patients (89%)...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388581/temozolomide-combined-with-irinotecan-caused-regression-in-an-adult-pleomorphic-rhabdomyosarcoma-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#3
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Takashi Murakami, Shinji Miwa, Scott D Nelson, Sarah M Dry, Yunfeng Li, Arun S Singh, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and recalcitrant, highly-malignant mesenchymal tumor in need of improved therapeutic strategies. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). We previously described the development of a PDOX model of adult pleomorphic RMS where the tumor behaved similar to the patient donor. A high-grade pleomorphic rhabdomyosarcoma from a striated muscle was previously grown orthotopically in the right biceps-femoris muscle of nude mice to establish the PDOX model...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28327932/integrated-safety-analysis-of-rolapitant-with-coadministered-drugs-from-phase-ii-iii-trials-an-assessment-of-cyp2d6-or-bcrp-inhibition-by-rolapitant
#4
S Barbour, T Smit, X Wang, D Powers, S Arora, V Kansra, M Aapro, J Herrstedt
Background: Rolapitant, a long-acting neurokinin (NK) 1 receptor antagonist (RA), has demonstrated efficacy in prevention of chemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlike other NK 1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325092/effectiveness-of-low-dose-oral-etoposide-treatment-in-patients-with-recurrent-and-platinum-resistant-epithelial-ovarian-cancer
#5
Yakup Bozkaya, Mutlu Doğan, Gökmen Umut Erdem, Gökhan Tulunay, Hikmet Uncu, Zafer Arık, Umut Demirci, Ozan Yazıcı, Nurullah Zengin
The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment...
March 21, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28278081/correlative-analysis-of-plasma-sn-38-levels-and-dpd-activity-with-outcomes-of-folfiri-regimen-for-metastatic-colorectal-cancer-with-ugt1a1-28-and-6-wild-type-and-its-implication-for-individualized-chemotherapy
#6
Xun Cai, Chuan Tian, Liwei Wang, Rongyuan Zhuang, Xiaowei Zhang, Yuanbiao Guo, Hongmin Lu, Hui Wang, Xiaoyu Li, Junwei Gao, Qi Li, Chungang Wang
It remains uncertain whether there is an correlation between clinical pharmacokinetic parameters and outcomes for metastatic colorectal cancer especially with UGT1A1 *28 and *6 wild type (*1/*1-*1/*1) for serious events associated with Irinotecan are largely excluded. This study retrospectively analyzed the relationship between Irinotecan metabolite levels and outcomes of UGT1A1 *1/*1-*1/*1 genotype arrangement. Blood samples (n = 244) were collected for analysis of plasma DPD activity (before first chemotherapy) and SN-38 levels (1...
March 4, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28213365/fda-approval-summary-tas-102
#7
Leigh Marcus, Steven J Lemery, Sachia Khasar, Emily Wearne, Whitney S Helms, Weishi Yuan, Kun He, Xianhua Cao, Jingyu Yu, Hong Zhao, Yaning Wang, Olen Stephens, Erika Englund, Rajiv Agarwal, Patricia Keegan, Richard Pazdur
FDA approved TAS-102 (Lonsurf, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35mg/m2 orally twice daily after meals on Days 1-5 and 8-12 of each 28-day cycle (n=534) or matching placebo (n=266)...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28197787/dermatux-phase-iv-trial-of-cetuximab-plus-folfiri-in-first-line-metastatic-colorectal-cancer-receiving-a-pre-defined-skin-care
#8
Carl Christoph Schimanski, Frank Staib, Thomas Göhler, Holger Hebart, Michael Heike, Michael Neise, Jochen Rudi, Thomas Geer, Gerrit Dingeldein, Claudia Lang, Peter Ehscheidt, Thomas Flohr, Klaus Maria Josten, Meinolf Karthaus, Alexander Schmittel, Jan Wierecky, Emil Boller, Martin Indorf, Marcus-Alexander Wörns, Peter R Galle, Markus Moehler
PURPOSE: Cetuximab-induced skin rash Gd3+ occurs in ≥16% patients (pts) (Heinemann et al., Lancet Oncol 15(10):1065-1075, 2014; Van Cutsem et al. J Clin Oncol 27(19):3117-25; 2009b). Survival, response, and toxicity parameters were re-evaluated under a pre-defined skin prophylaxis consistent of vitamin K1 ointment and oral doxycycline. METHODS: This is a national, multicenter, phase 4, first-line mCRC (K-RAS wt) trial. Pts received irinotecan 180 mg/m² (d1), FA 400 mg/m² (d1), 5-FU 400 mg/m² (d1), 5-FU 2400 mg/m² (d1-2), and cetuximab [400 mg/m² (d1), and then 250 mg/m² qw], prophylactic 0...
February 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28174488/a-pilot-phase-ii-study-of-neoadjuvant-triplet-chemotherapy-regimen-in-patients-with-locally-advanced-resectable-colon-cancer
#9
Haitao Zhou, Yan Song, Jun Jiang, Haitao Niu, Hong Zhao, Jianwei Liang, Hao Su, Zheng Wang, Zhixiang Zhou, Jing Huang
OBJECTIVE: This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer. METHODS: Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2), combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m(2) by 44 h infusion or capecitabine 1 g/m(2) or S-1 40-60 mg b...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28156640/efficacy-of-rolapitant-for-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-with-gastrointestinal-and-colorectal-cancers
#10
Karin Jordan, Bernardo Leon Rapoport, Ian D Schnadig, Martin Chasen, Sujata Arora, Daniel Powers, Lee Steven Schwartzberg
222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28133357/-a-case-of-unresectable-advanced-rectal-cancer-with-a-pancreatic-tumor-that-was-successfully-treated-with-folfirinox
#11
Nobushige Yabe, Shinji Murai, Hiroki Ozawa, Takahiro Yokose, Ippei Oto, Takahisa Yoshikawa, Kenjiro Kitasato, Hirotomo Shimizu, Kenji Kojima, Hirotoshi Hasegawa, Yuko Kitagawa
A 72-year-old man was admitted to our hospital department in September 2014 because of a positive fecal occult blood test.Colonoscopy showed a type 2 tumor in half of the AV 15 cm rectosigmoid colon.Histology of the biopsy indicated a moderately differentiated adenocarcinoma, and the RAS gene test found wild type.On CT examination, there were multiple liver lung metastases and a 30mm diameter tumor with pancreatic duct extension to the pancreatic body.A PET-CT examination had a high SUVmax at the same site...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28128439/second-line-systemic-therapy-for-metastatic-colorectal-cancer
#12
REVIEW
Simone Mocellin, Zora Baretta, Marta Roqué I Figuls, Ivan Solà, Marta Martin-Richard, Sara Hallum, Xavier Bonfill Cosp
BACKGROUND: The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. OBJECTIVES: To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016)...
January 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28123730/pseudocirrhosis-caused-by-regorafenib-in-an-advanced-rectal-cancer-patient-with-multiple-liver-metastases
#13
Kensuke Kumamoto, Shungo Endo, Noriyuki Isohata, Azuma Nirei, Daiki Nemoto, Kenichi Utano, Takuro Saito, Kazutomo Togashi
A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28111925/combination-of-bevacizumab-irinotecan-and-temozolomide-for-refractory-or-relapsed-neuroblastoma-results-of-a-phase-ii-study
#14
Shakeel Modak, Brian H Kushner, Ellen Basu, Stephen S Roberts, Nai-Kong V Cheung
BACKGROUND: The rationale for studying the combination of bevacizumab, irinotecan, and temozolomide (BIT) in neuroblastoma (NB) is based on the following: (i) vascular endothelial growth factor (VEGF) expression is associated with an aggressive phenotype, (ii) anti-VEGF antibody bevacizumab enhances irinotecan-mediated suppression of NB xenografts, (iii) bevacizumab safety has been established in pediatric phase I studies, and (iv) irinotecan + temozolomide (IT) is a standard salvage chemotherapy...
January 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28081543/randomised-phase-ii-trial-of-irinotecan-plus-s-1-in-patients-with-gemcitabine-refractory-pancreatic-cancer
#15
RANDOMIZED CONTROLLED TRIAL
T Ioka, Y Komatsu, N Mizuno, A Tsuji, S Ohkawa, M Tanaka, H Iguchi, A Ishiguro, M Kitano, T Satoh, T Yamaguchi, K Takeda, M Kida, K Eguchi, T Ito, M Munakata, T Itoi, J Furuse, C Hamada, Y Sakata
BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m(-2) on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS)...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28011980/potential-safety-concerns-of-tlr4-antagonism-with-irinotecan-a-preclinical-observational-report
#16
Janet K Coller, Joanne M Bowen, Imogen A Ball, Hannah R Wardill, Ysabella Z A van Sebille, Romany L Stansborough, Zenab Lightwala, Anthony Wignall, Joseph Shirren, Kate Secombe, Rachel J Gibson
PURPOSE: Irinotecan-induced gut toxicity is mediated in part by Toll-Like receptor 4 (TLR4) signalling. The primary purpose of this preclinical study was to determine whether blocking TLR4 signalling by administering (-)-naloxone, a TLR4 antagonist, would improve irinotecan-induced gut toxicity. Our secondary aim was to determine the impact of (-)-naloxone on tumour growth. METHODS: Female Dark Agouti (DA) tumour-bearing rats were randomly assigned to four treatments (n = 6 in each); control, (-)-naloxone (100 mg/kg oral gavage at -2, 24, 48, and 72 h), irinotecan (175 mg/kg intraperitoneal at 0 h), and (-)-naloxone and irinotecan...
December 23, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27938508/regorafenib-plus-folfiri-with-irinotecan-dose-escalated-according-to-uridine-diphosphate-glucuronosyltransferase-1a1-genotyping-in-patients-with-metastatic-colorectal-cancer
#17
Cheng-Jen Ma, Ching-Wen Huang, Yung-Sung Yeh, Hsiang-Lin Tsai, Huang-Ming Hu, I-Chen Wu, Tian-Lu Cheng, Jaw-Yuan Wang
We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between Oct 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m(2) 48 of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m(2) 49 of irinotecan...
November 17, 2016: Oncology Research
https://www.readbyqxmd.com/read/27909037/safety-and-efficacy-of-stereotactic-body-radiation-therapy-combined-with-s-1-simultaneously-followed-by-sequential-s-1-as-an-initial-treatment-for-locally-advanced-pancreatic-cancer-silapanc-trial-study-design-and-rationale-of-a-phase-ii-clinical-trial
#18
Xiaofei Zhu, Xiaoping Ju, Fei Cao, Fang Fang, Shuiwang Qing, Yuxin Shen, Zhen Jia, Yangsen Cao, Huojun Zhang
INTRODUCTION: Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine...
December 1, 2016: BMJ Open
https://www.readbyqxmd.com/read/27906628/role-of-genomic-factors-beyond-thymidylate-synthase-in-the-prediction-of-response-to-5-fluorouracil
#19
Godefridus J Peters, K Smid, E Meijer, C J van Groeningen, L G Leon
5-Fluorouracil (5FU) is still a major drug in combinations regimens for the treatment of colorectal cancer (CRC) both in the adjuvant and palliative setting. 5FU or its oral prodrug capecitabine is usually combined with irinotecan/oxaliplatin and the novel agents bevacizumab/cetuximab. Although this improved the outcome, the overall prognosis in patients with metastasized disease is still relatively poor. Although the target for 5FU, thymidylate synthase was shown to have a predictive value, this could only predict response in a subset of patients...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27858180/irinotecan-monotherapy-as-third-line-treatment-for-advanced-gastric-cancer-refractory-to-fluoropyrimidines-platinum-and-taxanes
#20
Takashi Nishimura, Satoru Iwasa, Kengo Nagashima, Natsuko Okita, Atsuo Takashima, Yoshitaka Honma, Ken Kato, Tetsuya Hamaguchi, Yasuhide Yamada, Yasuhiro Shimada, Narikazu Boku
BACKGROUND: Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan. METHODS: A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes...
November 17, 2016: Gastric Cancer
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