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Pooled Analysis of Safety and Efficacy of Oxaliplatin Plus Fluorouracil/Leucovorin Administered Bimonthly in Elderly Patients With Colorectal Cancer

Richard M. Goldberg, Isabelle Tabah-Fisch, Harry Bleiberg, Aimery de Gramont, Christophe Tournigand, Thierry Andre, Mace L. Rothenberg, Erin Green, Daniel J. Sargent

From the University of North Carolina, Chapel Hill, NC; Sanofi-Aventis; Hôpital Saint Antoine; Hôpital Tenon, Paris, France; Institut J Bordet, Bruxelles, Belgium; Vanderbilt Hospital, Nashville, TN; and the Mayo Clinic, Rochester, MN.

Address reprint requests to Daniel J. Sargent, PhD, Mayo Clinic, 200 1st St SW, Rochester, MN 55905; e-mail: sargent.daniel{at}mayo.edu

Purpose Oxaliplatin, fluorouracil, and leucovorin are commonly used to treat advanced and resected colorectal cancer. This analysis compares the safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly (FOLFOX4) in patients age younger than and at least 70 years.

Patients and Methods This retrospective analysis included 3,742 colorectal cancer patients (614 age 70) from four clinical trials testing FOLFOX4 in the adjuvant, first-, and second-line settings. End points included grade 3 adverse events, response rate (in advanced disease), progression or relapse-free survival, dose-intensity, and overall survival in the studies with mature survival data.

Results Grade 3 hematologic toxicity (neutropenia [43% v 49%; P = .04] and thrombocytopenia [2% v 5%; P = .04]) were significantly higher in older patients. Older age was not associated with increased rates of severe neurologic adverse events, diarrhea, nausea/vomiting, infection, overall incidence of grade 3 toxicity (63% v 67%; P = .15), or 60-day mortality (1.1% v 2.3%; P = .20). The relative benefit of FOLFOX4 versus control did not differ by age for response rate, progression or recurrence free-survival (hazard ratio, 0.70 for FOLFOX4 v control for age < 70, 0.65 for age 70; P = .42), or overall survival (hazard ratio, 0.77 age < 70, 0.82 age 70; P = .79). Dose-intensity did not differ by age at cycles 1, 3, 6, or 12.

Conclusion FOLFOX4 maintains its efficacy and safety ratio in selected elderly patients with colorectal cancer. Its judicious use should be considered without regard to patient age, although scant data are available among patients older than 80 years.

Supported by a grant from Sanofi-Aventis.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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