Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials
E. Van Cutsem,Paulo M. Hoff,Peter Harper,R M Bukowski,David Cunningham,P Dufour,Ullrich Graeven,J Lokich,S Madajewicz,Jean A. Maroun,John L. Marshall,Edith P. Mitchell,G. Perez-Manga,Ph. Rougier,Wolff Schmiegel,J. Schoelmerich,Alberto Sobrero,Richard L. Schilsky +17 more
TLDR
Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC, and is a suitable replacement for i.V.5-FU as the backbone of colorectal cancer therapy.Abstract:
This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.read more
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ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
E. Van Cutsem,Andrés Cervantes,René Adam,Alberto Sobrero,J.H.J.M. van Krieken,Dan Aderka,E. Aranda Aguilar,Alberto Bardelli,Al B. Benson,György Bodoky,Fortunato Ciardiello,André D'Hoore,Eduardo Díaz-Rubio,J.-Y. Douillard,Michel Ducreux,Alfredo Falcone,Axel Grothey,Thomas Gruenberger,Karin Haustermans,Volker Heinemann,Paulo M. Hoff,C.-H. Köhne,R. Labianca,Pierre Laurent-Puig,Brigette B.Y. Ma,Tim Maughan,Kei Muro,Nicola Normanno,Pia Österlund,Pia Österlund,Wim J.G. Oyen,Demetris Papamichael,George Pentheroudakis,Per Pfeiffer,Timothy J. Price,C.J.A. Punt,Jens Ricke,Arnaud Roth,R. Salazar,Werner Scheithauer,H.-J. Schmoll,Josep Tabernero,Julien Taieb,Sabine Tejpar,Harpreet Wasan,Takayuki Yoshino,Aziz Zaanan,Dirk Arnold +47 more
TL;DR: These ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
Journal ArticleDOI
Clinical practice guidelines in oncology
William J. Gradishar,Benjamin O. Anderson,Ron Balassanian,Sarah L. Blair,Harold J. Burstein,Amy E. Cyr,Anthony D. Elias,William B. Farrar,Andres Forero,Sharon H. Giordano,Matthew P. Goetz,Lori J. Goldstein,Steven J. Isakoff,Janice A. Lyons,P. Kelly Marcom,Ingrid A. Mayer,Beryl McCormick,Meena S. Moran,Ruth O'Regan,Sameer A. Patel,Lori J. Pierce,Elizabeth C. Reed,Kilian E. Salerno,Lee S. Schwartzberg,Amy Sitapati,Karen L. Smith,Mary Lou Smith,Hatem Soliman,George Somlo,Melinda L. Telli,John H. Ward,Rashmi Kumar,Dorothy A. Shead +32 more
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Journal ArticleDOI
Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology
Al B. Benson,Alan P. Venook,Lynette Cederquist,Emily Chan,Yi-Jen Chen,Harry S. Cooper,Dustin A. Deming,Paul F. Engstrom,Peter C. Enzinger,Alessandro Fichera,Jean L. Grem,Axel Grothey,Howard S. Hochster,Sarah E. Hoffe,Steven C. Hunt,Ahmed Kamel,Natalie Kirilcuk,Smitha S. Krishnamurthi,Wells A. Messersmith,Mary F. Mulcahy,James D. Murphy,Steven J. Nurkin,Leonard B. Saltz,Sunil Sharma,David Shibata,John M. Skibber,Constantinos T. Sofocleous,Elena M. Stoffel,Eden Stotsky-Himelfarb,Christopher G. Willett,Christina Wu,Kristina M. Gregory,Deborah A. Freedman-Cass +32 more
TL;DR: This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease and considers treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences.
Journal ArticleDOI
Capecitabine as Adjuvant Treatment for Stage III Colon Cancer
Chris Twelves,A. Wong,M. Nowacki,Markus Abt,Howard A. Burris,Alfredo Carrato,Jim Cassidy,Andrés Cervantes,Jan Fagerberg,Vassilis Georgoulias,Fares Husseini,Duncan I. Jodrell,P. Koralewski,Hendrik Kröning,Jean A. Maroun,Norbert Marschner,Joseph McKendrick,M. Pawlicki,Riccardo Rosso,Johannes Schüller,Jean-François Seitz,Borut Stabuc,Jerzy Tujakowski,Guy van Hazel,Jerzy Zaluski,Werner Scheithauer +25 more
TL;DR: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.
Journal ArticleDOI
Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
TL;DR: This work presents the results of a randomised, double-blind, placebo-controlled trial conducted at the University Hospitals Leuven and at the urging of the ESMO Guidelines Working Group to evaluate the safety and effectiveness of chemotherapy for Digestive Oncology patients with Hashimoto's disease.
References
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Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
A. de Gramont,A. Figer,M. Seymour,M. Homerin,A. Hmissi,J. Cassidy,Corrado Boni,H. Cortes-Funes,Andrés Cervantes,Gilles Freyer,Demetris Papamichael,N. Le Bail,C. Louvet,D. Hendler,F. de Braud,C. Wilson,Francois Morvan,Andrea Bonetti +17 more
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Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial
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Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer
Leonard B. Saltz,John Cox,Charles D. Blanke,Lee S. Rosen,Louis Fehrenbacher,Malcolm J. Moore,Jean A. Maroun,Stephen P. Ackland,Paula K. Locker,Nicoletta Pirotta,Gary Elfring,Langdon L. Miller +11 more
TL;DR: In this paper, the authors compared a combination of irinotecan, fluorouracil, and leucovorin with bolus doses of leucocil as first-line therapy for metastatic colorectal cancer.
Journal ArticleDOI
A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal Cancer
Richard M. Goldberg,Daniel J. Sargent,Roscoe F. Morton,Charles S. Fuchs,Ramesh K. Ramanathan,Stephen K. Williamson,B. Findlay,Henry C. Pitot,Steven R. Alberts +8 more
TL;DR: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe and should be considered as a standard therapy for patients with advanced colorectal cancer.
Journal ArticleDOI
A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal Cancer
Richard M. Goldberg,Daniel J. Sargent,Roscoe F. Morton,Charles S. Fuchs,Ramesh K. Ramanathan,Stephen K. Williamson,B. Findlay,Henry C. Pitot,Steven R. Alberts +8 more
TL;DR: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe and should be considered as a standard therapy for patients with advanced colorectal cancer.