Journal ArticleDOI
Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
Pascal Piedbois,Ph. Rougier,Marc Buyse,J.P. Pignon,Louise Ryan,R Hansen,Benny Zee,B Weinerman,J Pater,Cynthia G. Leichman,John S. Macdonald,Jacqueline Benedetti,J Lokich,J Fryer,G Brufman,R Isacson,Agnès Laplanche,E Levy +17 more
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TLDR
5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival, and the hematologic toxicity is much less important in patients who receive 5-fu CI, but hand-foot syndrome is frequent in this group of patients.Abstract:
PURPOSE The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.read more
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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.
Journal ArticleDOI
Clinical translation of angiogenesis inhibitors.
Robert S. Kerbel,Judah Folkman +1 more
TL;DR: Angiogenesis inhibitors are a new class of drugs, for which the general rules involving conventional chemotherapy might not apply, and clinical application depends partly on the transfer of expertise from scientists who are familiar with the biology of angiogenesis to clinicians.
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Antiangiogenic Scheduling of Chemotherapy Improves Efficacy against Experimental Drug-resistant Cancer
Timothy Browder,Catherine Butterfield,Birgit M. Kräling,Bin Shi,Blair Marshall,Michael S. O'Reilly,Judah Folkman +6 more
TL;DR: Using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, it is shown that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant.
Journal ArticleDOI
Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy
Scott Kopetz,George J. Chang,Michael J. Overman,Cathy Eng,Daniel J. Sargent,David W. Larson,Axel Grothey,Jean Nicolas Vauthey,David M. Nagorney,Robert R. McWilliams +9 more
TL;DR: Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients and advancements in medical therapy between 1998 and 2006.
References
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TL;DR: The drum mallets disclosed in this article are adjustable, by the percussion player, as to balance, overall weight, head characteristics and tone production of the mallet, whereby the adjustment can be readily obtained.
Journal ArticleDOI
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TL;DR: Efficient methods of analysis of randomized clinical trials in which the authors wish to compare the duration of survival among different groups of patients are described.
Journal ArticleDOI
Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate by the advanced colorectal cancer meta-analysis project
Pascal Piedbois,Marc Buyse,Y. Rustum,D. Machover,C. Erlichman,Robert W. Carlson,F. Valone,R. Labianca,James H. Doroshow,N. Petrelli +9 more
TL;DR: Tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer in future trials, according to a meta-analysis performed on nine randomized clinical trials.