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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/29159476/the-impact-of-skeletal-muscle-on-the-pharmacokinetics-and-toxicity-of-5-fluorouracil-in-colorectal-cancer
#1
Grant R Williams, Allison M Deal, Shlomit Strulov Shachar, Christine M Walko, Jai N Patel, Bert O'Neil, Howard L McLeod, Marc S Weinberg, Seul Ki Choi, Hyman B Muss, Hanna K Sanoff
PURPOSE: Great heterogeneity exists in the ability of adults with cancer to tolerate chemotherapy. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The objective of this exploratory study was to examine the association of low skeletal muscle, commonly known as sarcopenia, on the pharmacokinetics (PKs) of 5-fluorouracil (5FU) in patients receiving FOLFOX for colorectal cancer. METHODS: We performed a secondary analysis of a completed multicenter trial that investigated PK-guided 5FU dosing in patients receiving mFOLFOX6 +/- bevacizumab for colorectal cancer...
November 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29159475/correction-to-a-phase-i-randomized-single-dose-study-evaluating-the-pharmacokinetic-equivalence-of-biosimilar-abp-215-and-bevacizumab-in-healthy-adult-men
#2
Richard Markus, Vincent Chow, Zhiying Pan, Vladimir Hanes
The article [A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men].
November 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29149426/relationship-between-lat1-expression-and-resistance-to-chemotherapy-in-pancreatic-ductal-adenocarcinoma
#3
Bolag Altan, Kyoichi Kaira, Akira Watanabe, Norio Kubo, Pinjie Bao, Gantumur Dolgormaa, Erkhem-Ochir Bilguun, Kenichiro Araki, Yoshikatsu Kanai, Takehiko Yokobori, Tetsunari Oyama, Masahiko Nishiyama, Hiroyuki Kuwano, Ken Shirabe
PURPOSE: L-type amino acid transporter 1 (LAT1) is linked to tumor cell proliferation, angiogenesis, and survival in various human cancers. Although the expression of LAT1 was identified as a significant prognostic predictor after surgery in patients with pancreatic ductal adenocarcinoma (PDAC), little is known about the clinical significance of LAT1 as a chemotherapeutic resistance factor in PDAC. METHODS: A total of 110 patients with surgically resected PDAC were retrospectively reviewed as the training set...
November 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29143072/the-extent-of-ground-glass-attenuation-is-a-risk-factor-of-chemotherapy-related-exacerbation-of-interstitial-lung-disease-in-patients-with-non-small-cell-lung-cancer
#4
Takeshi Masuda, Chihiro Hirano, Yasushi Horimasu, Taku Nakashima, Shintarou Miyamoto, Hiroshi Iwamoto, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
OBJECTIVES: Chemotherapy-related acute exacerbation (AE) of interstitial lung disease (ILD) is observed in certain patients with non-small cell lung cancer (NSCLC) who have ILD. Although the prognosis of AE-ILD is extremely poor, there are no established risk factors for its occurrence. Therefore, we retrospectively investigated whether high-resolution computed tomography (HRCT) findings could identify risk factors for AE-ILD. MATERIALS AND METHODS: Between January 2005 and December 2016, 35 patients with NSCLC who received chemotherapy at Hiroshima University Hospital and were diagnosed with ILD on HRCT were enrolled...
November 15, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29134491/dpyd-2a-and-mthfr-c677t-predict-toxicity-and-efficacy-respectively-in-patients-on-chemotherapy-with-5-fluorouracil-for-colorectal-cancer
#5
Noor Ahmed Nahid, Mohd Nazmul Hasan Apu, Md Reazul Islam, Samia Shabnaz, Surid Mohammad Chowdhury, Maizbha Uddin Ahmed, Zabun Nahar, Md Siddiqul Islam, Mohammad Safiqul Islam, Abul Hasnat
BACKGROUND: Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients...
November 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29127457/the-promise-and-challenges-of-exploiting-the-proton-coupled-folate-transporter-for-selective-therapeutic-targeting-of-cancer
#6
REVIEW
Larry H Matherly, Zhanjun Hou, Aleem Gangjee
This review considers the "promise" of exploiting the proton-coupled folate transporter (PCFT) for selective therapeutic targeting of cancer. PCFT was discovered in 2006 and was identified as the principal folate transporter involved in the intestinal absorption of dietary folates. The recognition that PCFT was highly expressed in many tumors stimulated substantial interest in using PCFT for cytotoxic drug targeting, taking advantage of its high level transport activity under the acidic pH conditions that characterize many tumors...
November 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29124328/efficacy-of-combination-chemotherapy-using-irinotecan-and-nedaplatin-for-patients-with-recurrent-and-refractory-endometrial-carcinomas-preliminary-analysis-and-literature-review
#7
Morikazu Miyamoto, Masashi Takano, Mika Kuwahara, Hiroaki Soyama, Kento Kato, Hiroko Matuura, Takahiro Sakamoto, Kazuki Takasaki, Tadashi Aoyama, Tomoyuki Yoshikawa, Kenichi Furuya
PURPOSE: We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. METHODS: Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m(2) of CPT-11 on days 1, 8, and 15, and 50 mg/m(2) of nedaplatin on day 1, q4 weeks...
November 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29124327/a-phase-ii-study-of-biweekly-gemcitabine-and-carboplatin-in-completely-resected-stage-ib-iiia-non-small-cell-lung-cancer
#8
Reiko Sakurai, Yoshio Tomizawa, Akihiro Yoshii, Yosuke Miura, Hiroaki Tsurumaki, Kyoichi Kaira, Noriaki Sunaga, Osamu Kawashima, Takeshi Hisada, Masanobu Yamada, Ryusei Saito
PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of biweekly gemcitabine and carboplatin combination treatment in patients with resected non-small cell lung cancer (NSCLC). METHODS: Patients with completely resected stage IB to IIIA NSCLC were treated with four cycles of gemcitabine (1000 mg/m(2), days 1 and 15) plus carboplatin [area under the time-concentration curve (AUC) 5 mg/mL/min, day 1] every 4 weeks as adjuvant chemotherapy...
November 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#9
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29119292/population-pharmacokinetics-of-nintedanib-an-inhibitor-of-tyrosine-kinases-in-patients-with-non-small-cell-lung-cancer-or-idiopathic-pulmonary-fibrosis
#10
Ulrike Schmid, Karl-Heinz Liesenfeld, Angele Fleury, Claudia Dallinger, Matthias Freiwald
PURPOSE: A population pharmacokinetic model was developed for nintedanib in patients with non-small cell lung cancer (NSCLC) or idiopathic pulmonary fibrosis (IPF). The effects of intrinsic and extrinsic patient factors on exposure of nintedanib and its main metabolite BIBF 1202 were studied. METHODS: Data from 1191 patients with NSCLC (n = 849) or IPF (n = 342) treated with oral nintedanib (once- or twice-daily, dose range 50-250 mg) in 4 Phase II or III studies were combined...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29116379/phase-ii-study-of-nedaplatin-and-irinotecan-as-adjuvant-chemotherapy-for-completely-resected-non-small-cell-lung-cancer
#11
Shuji Murakami, Haruhiro Saito, Tetsuro Kondo, Hiroyuki Ito, Fumihiro Oshita, Kouzo Yamada
INTRODUCTION: Cisplatin-based chemotherapy is the standard adjuvant therapy for patients with completely resected stage II or III non-small cell lung cancer (NSCLC). However, the completion rate of four cycles of cisplatin-based chemotherapy is about 50%. This phase II study was conducted to evaluate the tolerability and efficacy of nedaplatin and irinotecan as adjuvant chemotherapy. METHODS: Patients with pathological stage II or III NSCLC who underwent complete resection were enrolled...
November 7, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29101463/a-drug-drug-interaction-study-to-assess-the-effect-of-the-cyp1a2-inhibitor-fluvoxamine-on-the-pharmacokinetics-of-dovitinib-tki258-in-patients-with-advanced-solid-tumors
#12
Vincent A de Weger, Sanjay Goel, Roger von Moos, Jan H M Schellens, Nicholas Mach, Eugene Tan, Suraj Anand, Jeffrey W Scott, Ulrik Lassen
PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: Non-smoking patients of ≥ 18 years with advanced solid tumors, excluding breast cancer, were included. Patients were treated with a dose of 300 mg in 5 days on/2 days off schedule...
November 3, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29098381/the-effects-of-lapatinib-on-cyp3a-metabolism-of-midazolam-in-patients-with-advanced-cancer
#13
Kevin M Koch, E Claire Dees, Shodeinde A Coker, Nandi J Reddy, Shelby D Gainer, Nikita Arya, Andrew P Beelen, Lionel D Lewis
PURPOSE: The potential inhibition of CYP3A4 by lapatinib was studied using midazolam as a probe substrate in patients with cancer. METHODS: This was a partially randomized, 4-period, 4-sequence, 4-treatment, cross-over study in 24 patients with advanced cancer. Single 1-mg IV and 3-mg oral doses of midazolam were given 2 days apart, in a partially random order, on study days 1, 3, 9, and 11. Lapatinib 1500-mg was administered orally once daily on study days 4 through 11...
November 2, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29094178/randomized-phase-iii-trial-comparing-surgery-alone-to-uft%C3%A2-%C3%A2-psk-for-stage-ii-rectal-cancer-jfmc38-trial
#14
Kiyotaka Okuno, Toru Aoyama, Koji Oba, Noboru Yokoyama, Nobuhisa Matsuhashi, Katsuyuki Kunieda, Yoji Nishimura, Hiroki Akamatsu, Takaya Kobatake, Satoshi Morita, Takaki Yoshikawa, Junichi Sakamoto, Shigetoyo Saji
BACKGROUND: We conducted a randomized phase III trial comparing tegafur/uracil (UFT) and Polysaccharide-K (PSK) to surgery alone in curatively resected stage II rectal cancer patients. METHODS: Patients were randomly assigned to receive either UFT and PSK or surgery alone in a 1:1 ratio with a minimization method to balance the treatment allocation. The primary end point of this study was the disease-free survival (DFS). The secondary end point was the overall survival (OS)...
November 1, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29086064/therapeutic-potential-of-the-metabolic-modulator-metformin-on-osteosarcoma-cancer-stem-like-cells
#15
Daniela I Paiva-Oliveira, Sara R Martins-Neves, Antero J Abrunhosa, Carlos Fontes-Ribeiro, Célia M F Gomes
PURPOSE: Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin. METHODS: Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay...
October 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29086063/evaluation-of-the-effect-of-new-formulation-food-or-a-proton-pump-inhibitor-on-the-relative-bioavailability-of-the-smoothened-inhibitor-glasdegib-pf-04449913-in-healthy-volunteers
#16
Nagdeep Giri, Lisa H Lam, Robert R LaBadie, Joseph F Krzyzaniak, Hong Jiang, Brian Hee, Yali Liang, M Naveed Shaik
PURPOSE: This phase I open-label study investigated the oral bioavailability of two novel maleate salt-based glasdegib (PF-04449913) tablet formulations (small- and large-particle size) relative to the current clinical formulation (diHCl salt-based). In addition, the effect of a gastric pH-altering agent (rabeprazole) and food on the pharmacokinetics of the large-particle size formulation of glasdegib were evaluated. The pharmacokinetics of glasdegib oral solution was also assessed. METHODS: Thirty-four healthy subjects received glasdegib 100 mg as three different formulations in the fasted state (diHCl salt or small- or large-particle size maleate formulation); 13 received the large-particle maleate formulation (fed), and 14 concurrently with rabeprazole (fasted); six subjects received glasdegib 50 mg oral solution (fasted)...
October 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29086062/correction-to-innovative-intraoral-cooling-device-better-tolerated-and-equally-effective-as-ice-cooling
#17
Java Walladbegi, Martin Gellerstedt, Anncarin Svanberg, Mats Jontell
Unfortunately, the online published article has error in Table 1. The correct Table 1 is given in the following page.
October 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29080971/combination-chemotherapy-with-irinotecan-and-gemcitabine-for-taxane-platinum-resistant-refractory-ovarian-and-primary-peritoneal-cancer-a-multicenter-phase-i-ii-trial-gogo-ov-6
#18
Kiyoshi Yoshino, Shoji Kamiura, Takeshi Yokoi, Ruriko Nakae, Masami Fujita, Masahiko Takemura, Kazushige Adachi, Akinori Wakimoto, Takamichi Nishizaki, Yasuhiko Shiki, Tateki Tsutsui, Yuki Kanda, Eiji Kobayashi, Kae Hashimoto, Seiji Mabuchi, Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu, Tadashi Kimura
PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m(2), respectively; level 2: 100 and 1000 mg/m(2)) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity...
October 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29080970/ibrutinib-does-not-prolong-the-corrected-qt-interval-in-healthy-subjects-results-from-a-thorough-qt-study
#19
Jan de Jong, Peter Hellemans, James Juhui Jiao, Yuhan Huang, Sofie Mesens, Juthamas Sukbuntherng, Daniele Ouellet
PURPOSE: Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. METHODS: Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval...
October 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29075856/the-potential-usefulness-of-the-response-index-in-positron-emission-tomography-assessing-the-therapeutic-effect-of-pre-operative-chemotherapy-for-advanced-colorectal-cancer
#20
Masatoshi Nomura, Hidekazu Takahashi, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Masakazu Ikenaga, Hirofumi Yamamoto, Kohei Murata, Yuichiro Doki, Masaki Mori, Tsunekazu Mizushima
BACKGROUND AND PURPOSE: Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer...
October 26, 2017: Cancer Chemotherapy and Pharmacology
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