Eloxatin Approved as First-Line Treatment of Metastatic Colorectal Cancer

ROCKVILLE, Maryland--Eloxatin (oxaliplatin, Sanofi-Synthelabo)has won marketing approval [Jan.2004] from the Food and Drug Administration(FDA) for the first-linetreatment of metastatic colorectal cancerin combination with fluorouraciland leucovorin (5-FU/LV), commonlycalled FOLFOX.The agency approved the company'sSupplemental New Drug Applicationbased on the results of a studysponsored by the National Cancer Institute.That study found that advancedcolorectal cancer patients treated withthe drug regimen had statistically significantimprovements in median survival-4.8 months-tumor response,and time to progression, comparedwith those treated with irinotecan(Camptosar) plus bolus 5-FU/LV."The finding that the oxaliplatinbasedregimen demonstrated a longersurvival time for patients is a majorstep forward," said Richard M. Goldberg,MD, University of North Carolina."This is the greatest increase insurvival time we have seen in a chemotherapyregimen used in advanced colorectalcancer." Dr. Goldberg servedas the study chair for the trial thatSanofi-Synthelabo submitted in supportof its FDA application.N9741
The study on which the FDA basedits approval was designated N9741 andsupervised by the North Central CancerTreatment Group. It randomizedpatients to the FOLFOX regimen or toreceive irinotecan plus 5-FU/LV (IFL).Patients in the FOLFOX arm had amedian survival of 19.4 months aftertreatment initiation vs 14.6 monthsfor those in the IFL group-a 38%survival advantage.The FOLFOX group also had a significantlyhigher overall tumor responserate in patients with measurabledisease, 45% vs 33%, as well as asignificantly longer time to diseaseprogression, 8.7 months vs 6.9 months.The commonly reported side ef-fects with FOLFOX included neutropeniaand paresthesia. However, studiesand clinical experience have shownan association of Eloxatin with potentiallyfatal pulmonary toxicity, andanaphylactic-like reactions that mayoccur minutes after drug administration.These reactions have been treatedwith epinephrine, corticosteroids,and antihistamines. Two kinds of primarilyperipheral sensory neuropathyhave been seen with Eloxatin-anacute, reversible type and a persistentform.The drug's labeling section carriesa black box warning that states: "Eloxatinshould be administered under thesupervision of a qualified physicianexperienced in the use of cancer chemotherapeuticagents. Appropriatemanagement of therapy and complicationsis possible only when adequatediagnostic and treatment facilities arereadily available."Eloxatin is approved in more than60 countries for the first- and/or second-line treatment of metastatic colorectalcancer, according to Paris-basedSanofi-Synthelabo, which said worldwidesales of the drug in 2003 wouldexceed $1 billion.