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colorectal stage II oxaliplatin

Carling Ursem, Katherine Van Loon, Alan Venook
In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward?...
May 2016: Cancer Journal
Nan Song, Katherine L Pogue-Geile, Patrick G Gavin, Greg Yothers, S Rim Kim, Nicole L Johnson, Corey Lipchik, Carmen J Allegra, Nicholas J Petrelli, Michael J O'Connell, Norman Wolmark, Soonmyung Paik
IMPORTANCE: Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit. OBJECTIVE: To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy...
September 1, 2016: JAMA Oncology
Michiro Takahashi, Kiyoshi Hasegawa, Masaru Oba, Akio Saiura, Junichi Arita, Yoshihiro Sakamoto, Eiji Shinozaki, Nobuyuki Mizunuma, Yutaka Matsuyama, Norihiro Kokudo
of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively...
August 2016: Investigational New Drugs
Duo Chen, Xianyu Wen, Young Seok Song, Ye-Young Rhee, Tae Hun Lee, Nam Yun Cho, Sae-Won Han, Tae-You Kim, Gyeong Hoon Kang
BACKGROUND: Low methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. Eastern Cooperative Oncology Group performance status (ECOG-PS) is a method to assess the functional status of a patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX). RESULTS: LINE-1 methylation and microsatellite instability were analyzed in stage III or high-risk stage II CRCs (n = 336)...
2016: Clinical Epigenetics
Jenny Drott, Hans Starkhammar, Karin Kjellgren, Carina Berterö
PURPOSE: The purpose of this study was to explore the experiences of oxaliplatin-induced neurotoxic side effects among patients with colorectal cancer (CRC) and how these side effects influenced their daily lives over time. METHODS: To assess neurotoxic side effects, ten patients were repeatedly interviewed. The patients were recruited from two hospitals in south of Sweden, had stage II-III CRC, and had been treated with adjuvant oxaliplatin postoperatively, from November 2013 to October 2015...
August 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Line S Tarpgaard, Camilla Qvortrup, Sune B Nygård, Signe L Nielsen, Diana R Andersen, Niels Frank Jensen, Jan Stenvang, Sönke Detlefsen, Nils Brünner, Per Pfeiffer
UNLABELLED: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC...
2015: BMC Cancer
Elisabeth J Kap, Petra Seibold, Dominique Scherer, Nina Habermann, Yesilda Balavarca, Lina Jansen, Manuela Zucknick, Natalia Becker, Michael Hoffmeister, Alexis Ulrich, Axel Benner, Cornelia M Ulrich, Barbara Burwinkel, Hermann Brenner, Jenny Chang-Claude
Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5-fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two-step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy...
June 15, 2016: International Journal of Cancer. Journal International du Cancer
Alessandro Ottaiano, Anna Nappi, Salvatore Tafuto, Guglielmo Nasti, Chiara De Divitiis, Carmela Romano, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Antonio Avallone, Maurizio Capuozzo, Monica Capozzi, Piera Maiolino, Vincenzo Quagliariello, Stefania Scala, Vincenzo Rosario Iaffaioli
BACKGROUND: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy. METHODS: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the x03C7;2 test...
2016: Oncology
Stacey A Cohen, Chen Wu, Ming Yu, Georgia Gourgioti, Ralph Wirtz, Georgia Raptou, Chryssa Gkakou, Vassiliki Kotoula, George Pentheroudakis, George Papaxoinis, Vasilios Karavasilis, Dimitrios Pectasides, Konstantine T Kalogeras, George Fountzilas, William M Grady
BACKGROUND: The CpG island methylator phenotype (CIMP) is a promising biomarker for irinotecan/5-fluorouracil/leucovorin chemotherapy for stage III colon cancer. In the present study, we evaluated whether CIMP is a prognostic biomarker for standard-of-care oxaliplatin-based adjuvant therapy. MATERIALS AND METHODS: The HE6C/05 trial randomized 441 patients with stage II-III colorectal adenocarcinoma to adjuvant XELOX (capecitabine, oxaliplatin) or modified FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin)...
June 2016: Clinical Colorectal Cancer
Marie Laurent, Gaétan Des Guetz, Sylvie Bastuji-Garin, Stéphane Culine, Philippe Caillet, Thomas Aparicio, Etienne Audureau, Muriel Carvahlo-Verlinde, Nicoleta Reinald, Christophe Tournigand, Thierry Landre, Aurélie LeThuaut, Elena Paillaud, Florence Canouï-Poitrine
OBJECTIVES: To assess nonfeasibility of adjuvant-modified FOLFOX6 chemotherapy in patients with stage II or III colorectal cancer. METHODS: Consecutive patients managed between 2009 and 2013 in 2 teaching hospitals in the Paris urban area were included in the CORSAGE (COlorectal canceR, AGe, and chemotherapy fEasability study) cohort study. Nonfeasibility was defined by the frequencies of empirical first-cycle dose reduction (>15%), early discontinuation (<12 cycles), and low relative dose intensity (RDI) (<0...
December 14, 2015: American Journal of Clinical Oncology
Yanhong Deng, Yue Cai, Yan Huang, Zihuan Yang, Yang Bai, Yanlu Liu, Xiuping Deng, Jianping Wang
BACKGROUND: SLFN11 was reported to be a predictive marker for DNA damage drugs. The study was to investigate whether SLFN11 expression is related to sensitivity to adjuvant oxaliplatin-based treatment in colorectal cancer. METHODS: A tissue microarray, made with specimens from consecutive 261 patients who received oxaliplatin based adjuvant chemotherapy, was stained with anti-SLFN11 antibody. The staining was dichotomized as high or low expression. SLFN11 expression was correlated to clinicopathological factors, KRAS exon 2 mutation and survival...
2015: BMC Cancer
Jin Gu, Pengju Chen
The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain...
October 2015: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Dae-Won Lee, Sae-Won Han, Yongjun Cha, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Ji Won Park, Seung-Bum Ryoo, Seung-Yong Jeong, Gyeong Hoon Kang, Kyu Joo Park, Tae-You Kim
BACKGROUND: Asian population has different body mass index (BMI) profile compared to Caucasian population. However, the effect of obesity and body weight gain in Asian colorectal cancer patients treated with adjuvant chemotherapy has not been studied thus far. METHODS: We have analyzed the association between disease-free survival (DFS) and obesity/body weight change during treatment in Korean stage III or high-risk stage II colorectal cancer patients treated with adjuvant 5-fluorouracil/ leucovorin/oxaliplatin...
2015: BMC Cancer
R Obermannova, L Dusek, K Greplova, J Jarkovsky, J Sterba, R Vyzula, R Demlova, L Zdrazilova-Dubska, D Valik
Vitamin D deficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy...
2015: Neoplasma
J M Baas, L L Krens, A J ten Tije, F Erdkamp, T van Wezel, H Morreau, H Gelderblom, H J Guchelaar
INTRODUCTION: Cetuximab is registered for use in colorectal cancer (CRC) patients with RAS wild-type tumours only. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification (prenylation) of KRAS. We hypothesize that the activated KRAS pathway in KRAS mutant tumors can be inhibited by simvastatin rendering these tumors sensitive to the EGFR inhibitor cetuximab. METHODS: A Simon two-stage, single-arm, phase II study was performed to test the efficacy and safety of the addition of simvastatin to cetuximab in patients with a KRAS mutation in their CRC tumour who were previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens...
December 2015: Investigational New Drugs
Hiroaki Nozawa, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
AIM: The postoperative administration of oxaliplatin reduces the frequency of relapse in selected patients with colorectal cancer following surgical resection. However, factors associated with recurrence despite adjuvant therapy are largely unknown. PATIENTS AND METHODS: We investigated 68 patients who were pathologically diagnosed with stage II or III colorectal cancer and received oxaliplatin-including chemotherapy, FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) or CapeOX (capecitabine and oxaliplatin), after curative surgery...
September 2015: Anticancer Research
Jung Ho Kim, Jeong Mo Bae, Hyeon Jeong Oh, Hye Seung Lee, Gyeong Hoon Kang
BACKGROUND: Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. METHODS: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy...
March 2015: Journal of Pathology and Translational Medicine
Brandon J Anderson, Lindsay L Peterson
Colorectal cancer is the third most common cancer diagnosed in the USA each year. Oxaliplatin, a platinum-based chemotherapy agent, is part of the standard adjuvant chemotherapy regimen FOLFOX (oxaliplatin with 5-fluorouracil [5-FU] and leucovorin [LV]) for the treatment of stage III and some high-risk stage II colorectal cancers. Although oxaliplatin is generally well tolerated, certain side effects such as nausea, vomiting, and peripheral neuropathy are common. We report a case of oxaliplatin-induced capillary-leak syndrome in a 63-year-old man undergoing his 12th and final cycle of FOLFOX for stage III colorectal cancer...
October 2016: Journal of Oncology Pharmacy Practice
Jara M Baas, Lisanne L Krens, Monique M Bos, Johanneke E A Portielje, Erdogan Batman, Tom van Wezel, Hans Morreau, Henk-Jan Guchelaar, Hans Gelderblom
Panitumumab has proven efficacy in patients with metastatic or locally advanced colorectal cancer patients, provided that they have no activating KRAS mutation in their tumour. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification of KRAS. We hypothesize that the activity of the RAS-induced pathway in patients with a KRAS mutation might be inhibited by simvastatin. This would theoretically result in increased sensitivity to panitumumab, potentially comparable with tumours with wild-type KRAS...
September 2015: Anti-cancer Drugs
Samy M AlGizawy, Hoda H Essa, Badawy M Ahmed
PURPOSE: The purpose of this prospective pilot study was to determine the efficacy of preoperative chemotherapy with six cycles of FOLFOX 6 (without radiation therapy) followed by radical surgery followed by six additional cycles of FOLFOX 6 for patients with stage II/III rectal cancer. PATIENTS AND METHODS: From January 2010 to January 2014, patients with locally advanced rectal cancer who met the eligibility criteria were enrolled in this study. Patients received FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium i...
July 2015: Oncologist
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