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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/29155512/efficacy-and-safety-of-cetuximab-plus-folfox-in-second-line-and-third-line-therapy-in-metastatic-colorectal-cancer
#2
Ersin Ozaslan, Ulas Serkan Topaloglu, Mevlude Inanc, Umut Gokmen Erdem, Hacer Demir, Erkan Arpaci, Mehmet Metin Seker, Mustafa Karaagac, Melih Kiziltepe, Baki Eker, Metin Ozkan
PURPOSE: To evaluate the efficacy and adverse events with cetuximab plus FOLFOX administered as second- and third-line therapy in metastatic colorectal cancer (mCRC) patients. METHODS: IPatients were administered cetuximab plus FOLFOX as second- and third-line therapy from January 2010 through October 2015. mCRC patients with wild type KRAS were alsï given irinïtecan and/ïr ïxaliplatin cïmbined with fluorïpyrimidine±bevacizumab. Tumor respïnse and survival were evaluated using RECIST and Kaplan-Meier methïd respectively...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29153096/correlations-between-microsatellite-instability-ercc1-xrcc1-polymorphism-and-clinical-characteristics-and-folfox-adjuvant-chemotherapy-effect-of-colorectal-cancer-patients
#3
Liping Zhang, Jiangman Zhao, Bin Yu, Xinjiang Song, Guogang Sun, Lijiang Han, Lu Wang, Shu Dong
Patients with MSI colorectal tumor have good prognosis and cannot benefit from 5-fluorouracil (5-Fu)-based chemotherapy reported by previous studies. While, single nucleotide polymorphisms (SNP) of ERCC1 and XRCC1 have be proved to influence clinical outcome of colorectal cancer patients treated with oxaliplatin-based chemotherapy. We aim to study the correlation between molecular status and clinical- pathological features, and their effect on CRC patients' clinical outcome treated with mFOLFOX6 adjuvant chemotherapy...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29140155/persistent-prevention-of-oxaliplatin-induced-peripheral-neuropathy-using-calmangafodipir-pledox-%C3%A2-a-placebo-controlled-randomised-phase-ii-study-pliant
#4
Bengt Glimelius, Nebojsa Manojlovic, Per Pfeiffer, Baadur Mosidze, Galina Kurteva, Mia Karlberg, Devalingam Mahalingam, Peter Buhl Jensen, Jan Kowalski, Marie Bengtson, Malin Nittve, Jacques Näsström
PURPOSE: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC). PATIENT AND METHODS: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2), oxaliplatin 85 mg/m(2) and 5-fluorouracil 2400 mg/m(2) continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible...
November 15, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29130943/effect-of-a-shortened-duration-of-folfox-chemotherapy-on-the-survival-rate-of-patients-with-stage-ii-and-iii-colon-cancer
#5
Woong Bae Ji, Kwang Dae Hong, Jung-Sik Kim, Sung-Yup Joung, Jun Won Um, Byung-Wook Min
BACKGROUND: FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. METHODS: Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer...
November 2, 2017: Chemotherapy
https://www.readbyqxmd.com/read/29113244/impact-of-the-individualization-of-the-first-line-chemotherapy-for-advanced-colorectal-cancer-based-on-collagen-gel-droplet-embedded-drug-sensitivity-test
#6
Takumi Ochiai, Kazuhiko Nishimura, Tomoo Watanabe, Masayuki Kitajima, Akinori Nakatani, Kiichi Nagayasu, Shigetoshi Naito, Tsuyoshi Sato, Kenji Kishine, Yu Abe, Chihiro Hara, Susumu Yamada, Satomi Mashiko, Isao Nagaoka
Leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) are widely used as first-line chemotherapy regimens in the treatment of advanced colorectal cancer (CRC). However, second-line chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost. Therefore, the most effective regimen should be selected as first-line chemotherapy. We reported that individualization of first-line treatment (FOLFOX/FOLFIRI/Dual/Poor responder) was possible using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) and that individualized first-line chemotherapy with CD-DST may improve the prognosis of patients with unresectable CRC...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29108355/a-phase-i-clinical-trial-of-binimetinib-in-combination-with-folfox-in-patients-with-advanced-metastatic-colorectal-cancer-who-failed-prior-standard-therapy
#7
May Cho, Jun Gong, Paul Frankel, Timothy W Synold, Dean Lim, Vincent Chung, Joseph Chao, Daneng Li, Yuan Chen, Stephen Sentovich, Kurt Melstrom, Gagandeep Singh, Eloise Luevanos, Marwan Fakih
Background: This was a first in-human, open-label, dose-escalation phase I study conducted to evaluate the maximum tolerated dose (MTD), safety, and efficacy of the combination of oral binimetinib and FOLFOX. Materials and Methods: Patients with metastatic colorectal cancer (mCRC) who progressed on prior standard therapies received twice daily binimetinib continuously or intermittently with FOLFOX. Dose-limiting toxicities (DLTs) were assessed in the first 2 cycles of study treatment...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104590/impact-of-body-mass-index-on-surgical-and-oncological-outcomes-in-laparoscopic-total-mesorectal-excision-for-locally-advanced-rectal-cancer-after-neoadjuvant-5-fluorouracil-based-chemoradiotherapy
#8
Yanwu Sun, Pan Chi
Aims: To evaluate the impact of body mass index (BMI) on the surgical outcome of laparoscopic total mesorectal excision (laTME) for locally advanced rectal cancer (LARC, clinically staged as UICC stage II/III) after neoadjuvant chemoradiotherapy (nCRT). Methods: 312 LARC patients undergoing laTME after nCRT were divided into nonobese (BMI < 25.0 kg/m(2), n = 249) and obese (BMI ≥ 25.0 kg/m(2), n = 63) groups. Preoperative radiotherapy was delivered in 45-50...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29090385/phase-ii-open-label-pilot-trial-of-aprepitant-and-palonosetron-for-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-receiving-moderately-emetogenic-folfox-chemotherapy-for-the-treatment-of-colorectal-cancer
#9
Joseph S Bubalo, Jon D Herrington, Marc Takemoto, Patricia Willman, Michael S Edwards, Casey Williams, Alan Fisher, Alison Palumbo, Eric Chen, Charles Blanke, Charles D Lopez
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients. METHODS: Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3...
October 31, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29065426/dihydropyrimidine-dehydrogenase-pharmacogenetics-for-predicting-fluoropyrimidine-related-toxicity-in-the-randomised-phase-iii-adjuvant-tosca-trial-in-high-risk-colon-cancer-patients
#10
RANDOMIZED CONTROLLED TRIAL
A Ruzzo, F Graziano, Fabio Galli, Francesca Galli, E Rulli, S Lonardi, M Ronzoni, B Massidda, V Zagonel, N Pella, C Mucciarini, R Labianca, M T Ionta, I Bagaloni, E Veltri, P Sozzi, S Barni, V Ricci, L Foltran, M Nicolini, E Biondi, A Bramati, D Turci, S Lazzarelli, C Verusio, F Bergamo, A Sobrero, L Frontini, M Menghi, M Magnani
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. METHODS: The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs)...
October 24, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29064002/cea-response-and-depth-of-response-dpr-to-predict-clinical-outcomes-of-first-line-cetuximab-treatment-for-metastatic-colorectal-cancer
#11
Yu Sunakawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Wataru Ichikawa
BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment...
October 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29061833/anti-epidermal-growth-factor-receptor-antibody-readministration-in-chemorefractory-metastatic-colorectal-cancer
#12
Tatsuhiro Kajitani, Akitaka Makiyama, Shuji Arita, Hozumi Shimokawa, Hisanobu Oda, Tsuyoshi Shirakawa, Eishi Baba, Taito Esaki
BACKGROUND/AIM: Readministration of anti-epidermal growth factor receptor (EGFR) antibody for metastatic colorectal cancer (mCRC) after disease progression remains to be determined. PATIENTS AND METHODS: Readministration of anti-EGFR antibody in mCRC patients previously refractory to anti-EGFR antibody was prospectively observed. RESULTS: A total of thirteen patients with a median age of 60-years old and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29061175/hepatic-artery-infusion-chemotherapy-using-mfolfox-versus-transarterial-chemoembolization-for-massive-unresectable-hepatocellular-carcinoma-a-prospective-non-randomized-study
#13
Min-Ke He, Yong Le, Qi-Jiong Li, Zi-Shan Yu, Shao-Hua Li, Wei Wei, Rong-Ping Guo, Ming Shi
BACKGROUND: Transarterial chemoembolization (TACE) is recommended as the standard care for unresectable hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage A-B. However, the efficacy of TACE on large (≥ 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy (HAIC) might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC...
October 23, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29045659/bevacizumab-chemotherapy-versus-chemotherapy-alone-in-elderly-patients-with-untreated-metastatic-colorectal-cancer-a-randomized-phase-ii-trial-prodige-20-study-results
#14
T Aparicio, O Bouché, J Taieb, E Maillard, S Kirscher, P-L Etienne, R Faroux, F Akouz Khemissa, F El Hajbi, C Locher, Y Rinaldi, T Lecomte, S Lavau-Denes, M Baconnier, A Oden-Gangloff, D Genet, E Paillaud, F Retornaz, E François, L Bedenne
BACKGROUND: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific endpoints in this population. PATIENTS AND METHODS: Patients aged 75 and over were randomly assigned to bevacizumab + chemotherapy (BEV) versus chemotherapy (CT)...
September 28, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29043514/efficacy-of-a-triplet-and-doublet-based-chemotherapy-as-first-line-therapy-in-patients-with-her2-negative-metastatic-gastric-cancer-a-retrospective-analysis-from-the-clinical-practice
#15
Maria Maddalena Laterza, Luca Pompella, Angelica Petrillo, Giuseppe Tirino, Annalisa Pappalardo, Michele Orditura, Teresa Troiani, Fortunato Ciardiello, Natale Di Martino, Ferdinando De Vita
The best choice of chemotherapy regimen for patients with metastatic gastric cancer is still debated. Although several studies support a superior efficacy of a triplet chemotherapy regimen over a doublet-based regimen, the magnitude of this benefit appears small and accompanied by an increased toxicity. Based on this background, we evaluated the outcome of patients with HER2-negative metastatic gastric cancer (mGC) who received in the clinical practice a triplet or doublet regimen as first-line therapy. A total of 165 patients (pts) with HER2-negative mGC treated outside of clinical trials at our department with FOLFOX-4 or ECX from 2012 and 2015 were included in our retrospective analysis: FOLFOX-4: 86 pts; ECX: 79 pts...
October 17, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29029527/targeted-first-line-therapies-for-advanced-colorectal-cancer-a-bayesian-meta-analysis
#16
Yassine Ridouane, Gilberto Lopes, Geoffrey Ku, Hasan Masud, Benjamin Haaland
BACKGROUND: Colorectal cancer is common and deadly. First-line treatments for patients with metastatic disease include FOLFIRI and FOLFOX, which have been combined with anti-EGFR or anti-VEGF antibodies to achieve benefit in selected populations. However, optimal therapy remains unclear. RESULTS: Fifteen publications on 10 trials were identified. There was a lack of decisive evidence that FOLFIRI or FOLFOX impact efficacy of either anti-EGFR or anti-VEGF, across mutational status groups...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026967/a-rat-model-of-folfox-induced-neuropathy-effects-of-oral-dimiracetam-in-comparison-with-duloxetine-and-pregabalin
#17
Lorenzo Di Cesare Mannelli, Mario Maresca, Laura Micheli, Carlo Farina, Michael W Scherz, Carla Ghelardini
BACKGROUND AND AIM: The FOLFOX family of chemotherapy regimens are hampered by the development of a painful neuropathy. Current clinical treatments are inadequate, and furthermore, the research of innovative drugs is strongly disadvantaged by the absence of a preclinical model based on the complete mixture of FOLFOX components. The aim of this study was to set up a rat model of FOLFOX-induced neuropathy in rats, validate its predictability by reference drugs, and evaluate the effectiveness of the new anti-neuropathic compound dimiracetam...
October 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29018169/randomized-phase-ii-trial-of-parsatuzumab-anti-egfl7-or-placebo-in-combination-with-folfox-and-bevacizumab-for-first-line-metastatic-colorectal-cancer
#18
Rocío García-Carbonero, Eric van Cutsem, Fernando Rivera, Jacek Jassem, Ira Gore, Niall Tebbutt, Fadi Braiteh, Guillem Argiles, Zev A Wainberg, Roel Funke, Maria Anderson, Bruce McCall, Mark Stroh, Eric Wakshull, Priti Hegde, Weilan Ye, Daniel Chen, Ilsung Chang, Ina Rhee, Herbert Hurwitz
No abstract text is available yet for this article.
October 2017: Oncologist
https://www.readbyqxmd.com/read/28983557/role-of-deficient-dna-mismatch-repair-status-in-patients-with-stage-iii-colon-cancer-treated-with-folfox-adjuvant-chemotherapy-a-pooled-analysis-from-2-randomized-clinical-trials
#19
Aziz Zaanan, Qian Shi, Julien Taieb, Steven R Alberts, Jeffrey P Meyers, Thomas C Smyrk, Catherine Julie, Ayman Zawadi, Josep Tabernero, Enrico Mini, Richard M Goldberg, Gunnar Folprecht, Jean Luc Van Laethem, Karine Le Malicot, Daniel J Sargent, Pierre Laurent-Puig, Frank A Sinicrope
Importance: The prognostic impact of DNA mismatch repair (MMR) status in stage III colon cancer patients receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) adjuvant chemotherapy remains controversial. Objective: To determine the association of MMR status with disease-free survival (DFS) in patients with stage III colon cancer treated with FOLFOX. Design, Setting, and Participants: The evaluated biomarkers for MMR status were determined from prospectively collected tumor blocks from patients treated with FOLFOX in 2 open-label, phase 3 randomized clinical trials: NCCTG N0147 and PETACC8...
October 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28982857/effect-of-hyperglycemia-on-antitumor-activity-and-survival-in-tumor-bearing-mice-receiving-oxaliplatin-and-fluorouracil
#20
Mai Ikemura, Tohru Hashida
BACKGROUND/AIM: Diabetic patients are at a higher risk of carcinogenesis and death from cancer, including colorectal cancer, than healthy individuals. The efficacy of cancer chemotherapy in the diabetic condition remains unclear. In this study, we investigated the efficacy of anticancer agents oxaliplatin and fluorouracil in streptozotocin (STZ)-treated hyperglycemic mice. MATERIALS AND METHODS: Starting 7 days after transplantation of colonic adenocarcinoma colon-26 cells, STZ-treated and control mice were intraperitoneally administered oxaliplatin, fluorouracil, and levofolinate (FOLFOX) every 2 weeks...
October 2017: Anticancer Research
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