ORLANDO-In first-line metastaticcolorectal cancer, capecitabine(Xeloda) is better tolerated than fluorouracil/leucovorin (5-FU/LV), and
ORLANDO-In first-line metastaticcolorectal cancer, capecitabine(Xeloda) is better tolerated than fluorouracil/leucovorin (5-FU/LV), andthe addition of capecitabine to oxaliplatin(Eloxatin)(XELOX) is both effectiveand tolerated, Hans-JoachimSchmoll, MD, PhD, said (abstract3523). Dr. Schmoll reported early safetyfindings from a phase III trial ofXELOX vs bolus 5-FU/LV as adjuvanttherapy for patients with stage III coloncancer."In the MOSAIC trial, oxaliplatin+ 5-FU/LV (FOLFOX4) resulted insuperior disease-free survival comparedwith 5-FU/LV and has recentlybeen approved for adjuvant therapy.As in metastatic colorectal cancer,capecitabine should be considered asan alternative to 5-FU/LV in combinationwith oxaliplatin in the adjuvantsetting. Therefore, we comparedthe safety and efficacy of XELOX withthose of bolus 5-FU/LV (the standardregimen at the start of the study) asadjuvant therapy for stage III coloncancer," Dr. Schmoll said.This ongoing study enrolled 1,886patients with resected stage III coloncancer. Patients were randomized toreceive XELOX (capecitabine: 1,000mg/m2 twice daily on days 1-14 +oxaliplatin: 130 mg/m2 on day 1, every3 weeks for eight cycles) or IV bolus 5-FU/LV (Mayo Clinic regimen: LV-20mg/m2 + 5-FU-425 mg/m2 on days 1-5, every 4 weeks for six cycles; orRoswell Park regimen: LV-500 mg/m2+ 5-FU-500 mg/m2 on day 1, for weeks1-6 in four 8-week cycles).Reduced Rate of FebrileNeutropeniaA total of 1,719 patients were evaluablefor safety. "There was a similarrate of related adverse events withXELOX and 5-FU/LV. There was lessgrade 3/4 stomatitis (1% vs 8%), neutropenia(8% vs 15%), and febrile neutropenia(< 1% vs 4%) with XELOXthan with 5-FU/LV. There was morefrequent grade 3 hand-foot syndrome(5% vs 1%) and grade 3/4 thrombocytopenia(5% vs 1%) with XELOX thanwith 5-FU/LV. Fifty-four percent ofXELOX patients and 45% of 5-FU/LVpatients experienced treatment-relatedgrade 3/4 adverse events. Sixty-dayall-cause mortality was 1% on botharms," Dr. Schmoll said."The lower rate of neutropenia withXELOX led to a reduced rate of grade3/4 febrile neutropenia," Dr. Schmollsaid.Dr. Schmoll and investigators concludedthat the safety data from thistrial indicate that XELOX is feasible inadjuvant treatment of colon cancerand compares favorably with FOLFOX4."XELOX appears to cause lessmyelosuppression and stomatitis butmore skin and neurosensory toxicitiesthan 5-FU/LV. XELOX has now beenincorporated in the three-arm AVANTadjuvant trial (FOLFOX4 vs FOLFOX4+ bevacizumab [Avastin] vs XELOX +bevacizumab)," Dr. Schmoll said. Efficacyresults are expected in 2007.