Adjuvant Capecitabine Bests Bolus 5-FU/LV in Patients With Dukes’ C Colon Cancer

August 1, 2005

ORLANDO-At a median follow-up of 51 months, data reported atASCO from the X-ACT phase III trial

ORLANDO-At a median follow-up of 51 months, data reported atASCO from the X-ACT phase III trialof capecitabine (Xeloda) vs bolus fluorouracil(5-FU)/leucovorin (LV) asadjuvant therapy for patients withDukes' C colon cancer confirm thatadjuvant capecitabine showed consistentbenefits over bolus 5-FU/LV, withat least equivalent disease-free survival(DFS) and a better safety profile,Christopher Twelves, MD, said (abstract3521)."The superior efficacy of capecitabineover 5-FU/LV in metastatic disease(response rate) has translated intosuperior efficacy in the adjuvant setting(relapse-free survival). These findingsprovide a very clear rationale forreplacing 5-FU/LV with capecitabinein the adjuvant treatment of colon cancer,"Dr. Twelves said.The X-ACT trial was undertaken toevaluate the efficacy of capecitabine vs5-FU/LV after studies showed superioractivity and improved safety fororal capecitabine compared with bolus5-FU/LV in first-line metastaticcolorectal cancer. The open-label, multinational,randomized, parallel-groupstudy enrolled 1,987 patients with resectedDukes' C colon carcinoma. Patientswere randomized to receive eitheroral capecitabine (1,250 mg/m2twice daily on days 1-14, every 3 weeks)or IV 5-FU/LV (Mayo Clinic regimen:LV-20 mg/m2 + 5-FU-425 mg/m2 ondays 1-5, every 4 weeks) for 24 weeks.Equivalent DFS, Better RFSThe primary study endpoint was atleast equivalence in DFS. Dr. Twelvessaid that the intent-to-treat analysisshowed at least equivalence in terms ofDFS between the treatment arms, witha strong trend toward superior DFSfor capecitabine (hazard ratio [HR] =0.87; 95% confidence interval [CI],0.75-1.00; P =.0525). At a median follow-up of 53 months, reported followingASCO, 3-year DFS was 66%with capecitabine vs 62.9% with 5-FU/LV (hazard ratio 0.87; P = .055).Relapse-free survival was significantlybetter for capecitabine. The HRof 0.89 translates into a significant14% reduction in risk of relapse withcapecitabine. Capecitabine causedsignificantly (P < .001) less all-gradediarrhea, nausea/vomiting, stomatitis,alopecia, and neutropenia and lessgrade 3/4 neutropenia, stomatitis,and neutropenic fever/sepsis than5-FU/LV. Capecitabine caused morenonlife-threatening hand-foot syndromeand hyperbilirubinemia than5-FU/LV (P < .001).Dr. Twelves concluded, "Multivariateanalysis showed that capecitabinetreatment has a significant impact onDFS (P = .015). The improved safetyprofile of capecitabine in the adjuvantsetting mirrors that observed in themetastatic setting. The high efficacy,improved safety, and convenience ofcapecitabine may increase the proportionof patients able and/or willingto benefit from adjuvant treatment."Adjuvant Xeloda ReceivesFDA ApprovalSince ASCO, the U.S. Food andDrug Administration (FDA) has approvedXeloda for use as single-agentadjuvant therapy following completeresection of the primary tumor forpatients with Dukes' C colon cancerwhen treatment with fluoropyrimidinetherapy alone is preferred. Approvalwas granted after review of datafrom the X-ACT trial (see page 6).