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Maintenance therapy metastatic colon cancer

Alexander Hann, Wolfram Bohle, Jan Egger, Wolfram Zoller
Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using induction chemotherapy followed by maintenance therapy from 2011 until November 2016 was collected and analyzed retrospectively...
January 31, 2017: Scientific Reports
Yuval Shaked, Elizabeth Pham, Santosh Hariharan, Ksenia Magidey, Ofrat Beyar-Katz, Ping Xu, Shan Man, Florence T H Wu, Valeria Miller, David Andrews, Robert S Kerbel
Conventional chemotherapy drugs administered at a maximum tolerated dose (MTD) remains the backbone for treating most cancers. Low-dose metronomic (LDM) chemotherapy, which utilizes lower, less toxic, doses given on a close regular basis over prolonged periods, is an alternative and better tolerated potential strategy to improve chemotherapy. LDM chemotherapy has been evaluated preclinically and clinically and has shown therapeutic benefit, in both early and advanced stage metastatic disease, especially when used as a maintenance therapy...
October 15, 2016: Cancer Research
Peter R Gibson, Brian G Feagan, William J Sandborn, Colleen Marano, Richard Strauss, Jewel Johanns, Lakshmi Padgett, Judith Collins, Dino Tarabar, Zbigniew Hebzda, Paul Rutgeerts, Walter Reinisch
OBJECTIVES: The safety and efficacy of subcutaneous golimumab through 2 years of maintenance therapy was evaluated in patients with moderate-to-severe ulcerative colitis (UC). METHODS: Patients completing treatment through week 52 (placebo, golimumab 50, 100, every-4-weeks (q4w)) and evaluations at week 54 were eligible for this long-term extension (LTE) trial. Patients receiving placebo or golimumab 50 mg with worsening disease during the LTE could receive golimumab 100 mg...
April 28, 2016: Clinical and Translational Gastroenterology
Michela Murdocca, Ruggiero Mango, Sabina Pucci, Silvia Biocca, Barbara Testa, Rosamaria Capuano, Roberto Paolesse, Massimo Sanchez, Augusto Orlandi, Corrado di Natale, Giuseppe Novelli, Federica Sangiuolo
The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge. CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis. Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (P<0...
March 22, 2016: Oncotarget
Baris Bayraktar, Ibrahim Ali Ozemir, Umut Kefeli, Gokhan Demiral, Julide Sagiroğlu, Onur Bayraktar, Gupse Adali, Alp Ozcelik, Osman Baran Tortum
AIM: To evaluate the long-term effectiveness of colonic stents in colorectal tumors causing large bowel obstruction. METHODS: We retrospectively analyzed data from 49 patients with colorectal cancer who had undergone colorectal stent placement between January 2008 and January 2013. Patients' symptoms, characteristics and clinicopathological data were obtained by reviewing medical records. The obstruction was diagnosed clinically and radiologically. Histopathological diagnosis was achieved endoscopically...
August 21, 2015: World Journal of Gastroenterology: WJG
Catherine Louise Penman, Claire Faulkner, Stephen P Lowis, Kathreena M Kurian
The mitogen-activated protein kinase (MAPK) pathway is known to play a key role in the initiation and maintenance of many tumors as well as normal development. This often occurs through mutation of the genes encoding RAS and RAF proteins which are involved in signal transduction in this pathway. BRAF is one of three RAF kinases which act as downstream effectors of growth factor signaling leading to cell cycle progression, proliferation, and survival. Initially reported as a point mutation (V600E) in the majority of metastatic melanomas, other alterations in the BRAF gene have now been reported in a variety of human cancers including papillary thyroid cancer, colon carcinomas, hairy cell leukemia, and more recently in gliomas...
2015: Frontiers in Oncology
Anne Marie C Flaherty
A 65-year-old Polish immigrant named T. J. was diagnosed with metastatic colon cancer in January 2012 when he presented with obstructing sigmoid colon cancer and liver metastases. A diverting colostomy as well as biopsy of his liver metastases was performed and chemotherapy with FOLFOX (5-fluorouracil [5-FU], leucovorin, oxaliplatin) and bevacizumab was initiated. After three months, he transitioned to maintenance therapy with infusional 5-FU and bevacizumab until he progressed in August 2012. Oxaliplatin was reintroduced and he responded until he developed progressive neuropathy in November and his therapy was changed to FOLFIRI (5-FU, leucovorin, irinotecan) and bevacizumab...
January 2015: Oncology Nursing Forum
Nivin Haroon, Syed M Raza, Zeenat Y Bhat
Magnesium is the second most common intracellular cation after potassium and plays pivotal role in the majority of metabolic process. Several studies have shown the prevalence of hypomagnesemia ranging from 2.5% to 12% in general population and even up to 60% in intensive care unit patients. Hypomagnesemia might be more prevalent in patients with cancer owing to a combination of several factors such as gastrointestinal loss, renal loss, poor intake, and use of certain chemotherapeutic drugs. It is imperative that we identify the exact cause of hypomagnesemia to aid and guide treatment...
July 2016: American Journal of Therapeutics
N K Chan, K G Abdullah, D Lubelski, M P Steinmetz, E C Benzel, J H Shin, T E Mroz
Spinal metastases invariably affect the majority of patients with cancer. Many will develop symptoms related to pain and disability from epidural spinal cord compression as well as pathologic fracture of the vertebrae. With the emergence of targeted systemic therapies and a better understanding of cancer biology, patients are living longer with bony metastases. This poses particular challenges, as palliation of pain and maintenance of local tumor control are paramount to quality of life and overall functional independence for these patients...
March 2014: Journal of Neurosurgical Sciences
Sanchita Roy, Adhip Pn Majumdar
: Colorectal cancer is the fourth most common form of cancer worldwide and ranks third among the cancer-related deaths in the US and other Western countries. It occurs with equal frequency in men and women, constituting 10% of new cancer cases in men and 11% in women. Despite recent advancement in therapeutics, the survival rates from metastatic are less than 5%. Growing evidence supports the contention that epithelial cancers including colorectal cancer, the incidence of which increases with aging, are diseases driven by the pluripotent, self-renewing cancer stem cells (CSCs)...
2012: Journal of Molecular Signaling
Christina Hackl, Shan Man, Giulio Francia, Chloe Milsom, Ping Xu, Robert S Kerbel
OBJECTIVE: Advanced and recurrent diseases are the major causes of death in colon cancer. No standard preclinical model addresses advanced disease and spontaneous metastasis after orthotopic tumour growth. In this study, the authors report the establishment of such standardised orthotopic mouse models of colon cancer and their use in evaluating metronomic topotecan alone or in combination with standard chemotherapy. DESIGN: Human colon cancer cell lines, transfected with human chorionic gonadotropin and luciferase, were injected orthotopically into the caecal wall of severe combined immunodeficient mice, intrasplenically or subcutaneously...
February 2013: Gut
Benoist Chibaudel, Christophe Tournigand, Thierry André, Aimery de Gramont
While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals...
March 2012: Therapeutic Advances in Medical Oncology
Sebastian M Dieter, Claudia R Ball, Christopher M Hoffmann, Ali Nowrouzi, Friederike Herbst, Oksana Zavidij, Ulrich Abel, Anne Arens, Wilko Weichert, Karsten Brand, Moritz Koch, Jürgen Weitz, Manfred Schmidt, Christof von Kalle, Hanno Glimm
Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term TICs (LT-TICs) maintained tumor formation in serial xenotransplants. Tumor transient amplifying cells (T-TACs) with limited or no self-renewal capacity contributed to tumor formation only in primary mice...
October 4, 2011: Cell Stem Cell
Sanjib Chowdhury, Gillian M Howell, Ashwani Rajput, Carol A Teggart, Lisa E Brattain, Hannah R Weber, Aparajita Chowdhury, Michael G Brattain
BACKGROUND: Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site...
2011: PloS One
F Giuliani, F De Vita, G Colucci, S Pisconti
In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy...
November 2010: Cancer Treatment Reviews
Manuela Gonzalez-Aparicio, Pilar Alzuguren, Itsaso Mauleon, Jose Medina-Echeverz, Sandra Hervas-Stubbs, Uxua Mancheno, Pedro Berraondo, Julien Crettaz, Gloria Gonzalez-Aseguinolaza, Jesus Prieto, Ruben Hernandez-Alcoceba
BACKGROUND AND AIMS: New options are needed for the management and prevention of colorectal cancer liver metastases. Interleukin 12 (IL-12) is an immunostimulatory cytokine with proven antitumour effect in animal models. Despite evidence indicating its biological effect in humans, neither the recombinant protein nor gene therapy vectors expressing IL-12 have shown a relevant benefit in patients with cancer. OBJECTIVE: To develop a new approach to overcome the difficulties in obtaining a suitable expression pattern and the immunosuppressive milieu in the tumours which contribute to this poor performance...
March 2011: Gut
Anne-Frédérique Dessein, Laurence Stechly, Nicolas Jonckheere, Patrick Dumont, Didier Monté, Emmanuelle Leteurtre, Stéphanie Truant, François-René Pruvot, Martin Figeac, Mohamed Hebbar, Charles-Henri Lecellier, Thécla Lesuffleur, Rodrigue Dessein, Georges Grard, Marie-José Dejonghe, Yvan de Launoit, Yasuhiro Furuichi, Grégoire Prévost, Nicole Porchet, Christian Gespach, Guillemette Huet
Metastasis and drug resistance are major problems in cancer chemotherapy. The purpose of this work was to analyze the molecular mechanisms underlying the invasive potential of drug-resistant colon carcinoma cells. Cellular models included the parental HT-29 cell line and its drug-resistant derivatives selected after chronic treatment with either 5-fluorouracil, methotrexate, doxorubicin, or oxaliplatin. Drug-resistant invasive cells were compared with noninvasive cells using cDNA microarray, quantitative reverse transcription-PCR, flow cytometry, immunoblots, and ELISA...
June 1, 2010: Cancer Research
Bert H O'Neil, Richard M Goldberg
It has been estimated that cancer of the colon and rectum (CRC) would be diagnosed in 153,760 men and women in the U.S. alone in 2007. Approximately one in five patients has metastatic CRC (mCRC) at diagnosis, which, at best, is associated with a 5-year survival rate of just 10.3%. Oxaliplatin- and irinotecan-based combination regimens are standard first-line therapies for mCRC. Recent studies suggest that survival outcomes can possibly be further improved by adding biologic agents to chemotherapy. Novel treatment strategies are being investigated to optimize the opportunity for patients to receive and benefit from the increasing number of available active agents and to further improve the efficacy, safety, and tolerability of multiagent therapy...
October 2008: Oncologist
Takayuki Suto, Naoko Ito, Toru Obuchi, Noriyuki Uesugi, Tamotsu Sugai, Shin-Ich Nakamura, Go Wakabayashi
We reported a case of sigmoid colon cancer with left supraclavicular lymph node involvement that completely responded to FOLFOX4 therapy following laparoscopy-assisted colectomy (LAC). A 69-year-old female presented with left supraclavicular tumor and was diagnosed as sigmoid colon cancer. Abnormally high CEA (128 ng/mL) and CA19-9 (59.3 U/mL) levels were detected in serum. She was operated palliatively by LAC, and FOLFOX4 therapy was initiated. The serum CEA and CA19-9 values regained their normal level after 5 and 4 courses of FOLFOX4, respectively...
April 2008: Gan to Kagaku Ryoho. Cancer & Chemotherapy
John Marshall
The current standard of care for the treatment of metastatic colorectal cancer involves at least six different regimens, and with the advent of new therapies, including biologic therapies, patients are projected to live beyond an average of 2 years. Data suggest a synergy between the biologics, which are in their infancy in terms of utilization, and they are being tested in the adjuvant setting in stage II and stage III disease. Ongoing and future trials will determine how best to incorporate these medicines into combination chemotherapy and determine if these medicines (or others) will have a role in maintenance chemotherapy for patients with metastatic colon cancer...
December 2006: Seminars in Oncology
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