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

March 1, 2004

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

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.