Journal ArticleDOI
Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
David Cunningham,Yves Humblet,Salvatore Siena,David Khayat,Harry Bleiberg,Armando Santoro,D. Bets,M. Mueser,Andreas Harstrick,Chris Verslype,Ian Chau,Eric Van Cutsem +11 more
TLDR
Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with ir inotecans-refractory colorectal cancer.Abstract:
background The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan. methods We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment. results The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combinationtherapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone. conclusions Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.read more
Citations
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Journal ArticleDOI
Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group
Malcolm J. Moore,David Goldstein,John T. Hamm,Arie Figer,J. R. Hecht,Steven Gallinger,Heather J. Au,Pawel Murawa,David Walde,Robert A. Wolff,D. M. B. Campos,Robert Lim,Keyue Ding,Gary M. Clark,Theodora Voskoglou-Nomikos,Mieke Ptasynski,Wendy R. Parulekar +16 more
TL;DR: To the authors' knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine.
Journal ArticleDOI
Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
Eric Van Cutsem,Claus Henning Köhne,Erika Hitre,J. Zaluski,Chung Rong Chang Chien,A. Makhson,Geert R. D'Haens,Tamás Pintér,Robert Lim,György Bodoky,Jae Kyung Roh,Gunnar Folprecht,Paul Ruff,Christopher Stroh,Sabine Tejpar,Michael Schlichting,Johannes Nippgen,Philippe Rougier +17 more
TL;DR: In this paper, the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer was investigated.
Journal ArticleDOI
K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
Christos S. Karapetis,Shirin Khambata-Ford,Derek J. Jonker,Christopher J. O'Callaghan,Dongsheng Tu,Niall C. Tebbutt,R. John Simes,Haji Chalchal,Jeremy Shapiro,Sonia Robitaille,Timothy J. Price,Lois E. Shepherd,Heather-Jane Au,Christiane Langer,Malcolm J. Moore,John Zalcberg +15 more
TL;DR: Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ra did benefit fromcetuxIMab.
Journal ArticleDOI
Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer
Rafael G. Amado,Michael S. Wolf,Marc Peeters,Eric Van Cutsem,Salvatore Siena,Daniel J. Freeman,Todd Juan,Robert Sikorski,Sid Suggs,Robert Radinsky,Scott D. Patterson,David D. Chang +11 more
TL;DR: Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors, and KRAS status should be considered in selecting patients withmCRC as candidates for panitumuab mon Therapy.
Journal ArticleDOI
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.
TL;DR: The current status of the different approaches and targets that are under evaluation and development for the therapeutic intervention of this key signaling pathway in human disease are summarized.
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