XELOX Safe, Effective as First-Line Therapy for Metastatic Colorectal Cancer

CHICAGO-In patients withmetastatic colorectal cancer, the combinationof oxaliplatin (Eloxatin) andcapecitabine (Xeloda) (XELOX) comparesfavorably with oxaliplatin/fluorouracil(5-FU)/leucovorin (LV) regimens(eg, FOLFOX) as first-linetherapy, according to a presentationat the 39th Annual Meeting of theAmerican Society of Clinical Oncology(ASCO abstract 1023). XELOX offersthe advantage of improved convenience.Oral capecitabine generates 5-FUpreferentially in tumors. Because ofits superior activity and improved safety,oral capecitabine has been replacingintravenous 5-FU/LV monotherapyin first-line metastatic colorectalcancer, noted Eric Van Cutsem, MD,PhD, University Hospital, Leuven, Belgium.Also, adding oxaliplatin to infused5-FU/LV improves efficacy.Oxaliplatin and capecitabine havedifferent mechanisms of action andhave safety profiles that do not overlap.Furthermore, capecitabine requiresonly one clinic visit every 3weeks. Therefore, substituting capecit-abine for 5-FU/LV should provide effective,safe, and convenient treatment,Prof. Van Cutsem said.To evaluate XELOX, the investigatorsenrolled 96 patients in an internationalphase II trial to receive intravenousoxaliplatin 130 mg/m² on day 1,followed by oral capecitabine 1,000mg/m² twice daily (evening of day 1through the morning of day 15) every3 weeks.The patients (64% men, medianage 64) had measurable metastatic colorectalcancer, Karnofsky performancestatus (KPS) greater than 70, life expectancyof 3 months or more, noprior chemotherapy with oxaliplatin,capecitabine, or irinotecan (Camptosar)in the metastatic setting, and noprior adjuvant therapy within 6months of enrollment.Primary tumors were in the colonin 63% and in the rectum in 33% (4%both). More than half of the patients(54%) had more than one metastaticsite (77% liver, 32% lung). Mediannumber of cycles of therapy was nine(range 1 to 46), with 30% of patientscontinuing capecitabine monotherapy(median, two cycles) after oxaliplatinwas stopped.Study Results
After a minimum follow-up of 24months, the overall response rate was55% (independent review assessment45%). Median progression-free survivalwas 7.7 months, and median overallsurvival was 19.5 months, with1-year survival of 71%.Subgroup evaluation (liver or lungmetastases, prior adjuvant chemotherapy,KPS of 80 vs more than 80, ageless than 60 vs 60 or more) revealedresponse rates (by investigator) consistentlygreater than 50%.Prof. Van Cutsem pointed out thatthe XELOX response rates comparedfavorably with those of other current5-FU/LV (bolus/infusion) plus oxaliplatinregimens (de Gramont 50%,Goldberg 38%), as did progressionfreesurvival (de Gramont 8.2 months,Goldberg 8.8 months) and overall survival(de Gramont 16.2 months,Goldberg 18.6 months).Prof. Van Cutsem noted that 70%of the patients have received poststudychemotherapy. The most commonregimen was irinotecan with or without5-FU.Sensory neuropathy (85%) and gastrointestinaldisturbances (diarrhea66%, nausea and vomiting 73%) werethe most common treatment-relatedadverse events. Grade 3/4 diarrhea wasseen in about 18% of patients, nausea/vomiting in about 14%, and handonifoot syndrome in 3%. In view of thelong duration of treatment, investigatorsconsidered it "impressive" that50% of patients received full-dosecapecitabine/oxaliplatin throughout.One death from respiratory failurewas attributed to study treatment. Thisknown, rare side effect of oxaliplatinoccurred in a patient with pre-existingpulmonary fibrosis.Side effects of XELOX, as comparedwith the de Gramont and Goldbergregimens, were similar, but withmuch reduced neutropenia (7%XELOX vs 42% de Gramont/47%Goldberg).Prof. Van Cutsem concluded thatas first-line therapy for metastatic colorectalcancer, XELOX offers highefficacy, good tolerability, andsubstantially improved convenience,compared with regimens combiningoxaliplatin with infusional 5-FU. PhaseIII trials of XELOX vs FOLFOX arefurther assessing the potential for replacing5-FU/LV as the backbone ofcolorectal cancer therapy.