Eloxatin Receives FDA Indication for Use in Adjuvant Treatment of Stage III Colon Cancer

ROCKVILLE, Maryland-The FDA approved a new indicationfor Eloxatin (oxaliplatin for injection,Sanofi-Synthelabo) in 2004-as atreatment combined with conventionalchemotherapy for the postsurgicaltreatment of patients with stage IIIcolon cancer after complete tumor resection.The drug, as with its previoustwo US approvals, is to be used incombination with infusional fluorouracil/leucovorin (5-FU/LV)."Early postsurgical treatment withthis Eloxatin-based regimen offers patientsthe greatest opportunity of livinglonger without recurrence of theirdisease," said John L. Marshall, MD,of Georgetown University.The FDA initially approved Eloxatinin August 2002 for the second-linetreatment of advanced colorectal cancer,and granted it first-line approvalin January 2004. The new approvalwas based on the MOSAIC study, aninternational phase III trial that involved2,246 patients treated at 146medical facilities. Participants wererandomized to receive either Eloxatinplus infusional 5-FU/LV or infusional5-FU/LV alone.MOSAIC Phase III StudyAt a median follow-up of 4 years,patients receiving Eloxatin showed asignificant improvement in diseasefreesurvival, the study's primary endpoint,compared with patients receivingplacebo. Overall, the treatmentarm had a 4-year disease-free survivalrate of 75.9%, compared with 69.1%for the control group (P = .0008).Among patients with stage III disease,those receiving Eloxatin had a 69.7%disease-free survival rate vs 61.0% forthe control arm (P = .002). The Eloxatin/5-FU/LV group had a 24% lowerrisk of cancer recurrence than the over-all patient population that had undergonesurgery to remove their primarytumor.The researchers noted that maturesurvival data were not available at 4years follow-up, and there was no statisticaldifference in overall survival ineither the full study population or inpatients with stage III disease. Moreover,stage II patients showed no statisticaldifference in disease-free survival,although a trend favored thetreatment arm, 85.1% vs 81.3%.Grade 3-4 ToxicityThe incidence of grade 3-4 adverseevents in the MOSAIC study was morethan double in the Eloxatin group,compared with the control patients:70% vs 31%. The most common grade3-4 events were granulocytopenia, paresthesia,diarrhea, vomiting, and nausea."Paresthesia was seen in 92% ofpatients on the Eloxatin combination;21% had residual paresthesia at 18-month follow-up," Sanofi-Synthelabosaid. "Three percent and 0.5% hadgrade 2-3 paresthesias, respectively, at18-month follow-up.Grade 3 and 4 hypersensitivity wasnoted in 3% and may require discontinuationof therapy, the companysaid. Hepatotoxicity evidenced by increasein transaminases (57% vs 34%)and alkaline phosphatases (42% vs20%) was observed more commonlyin the Eloxatin arm. Anaphylacticlikereactions to Eloxatin may occurwithin minutes after administrationof the drug, and its labeling states thatthe drug should be infused only underthe supervision of a qualified physician.In its letter to Sanofi-Synthelabo,the FDA also added immunoallergichemolytic anemia and colitis(including Clostridium difficile diarrhea)to the list of adverse reactionsassociated with Eloxatin.