Multinational Trial Supports Use of Capecitabine Plus Oxaliplatin for Metastatic Colorectal Cancer

CHICAGO-As first-line treatmentfor metastatic colorectal cancer,XELOX, the combination of oral capecitabine(Xeloda) plus oxaliplatin (Eloxatin),is safe and effective. These matureresults of a multinational trial (ASCO abstract1023) were reported by ProfessorEric Van Cutsem, MD, PhD, senior academicstaff member at University Hospital-Gasthuisberg, Leuven, Belgium.Dr. Van Cutsem noted that a significantfeature of capecitabine is the substantiallyimproved convenience that itoffers compared with infusional 5-FU.XELOX requires only one clinic visit every3 weeks, simplifying therapy and allowingthe patient to lead a more normallifestyle.According to Dr. Van Cutsem, "tumor-activated capecitabine was designedto mimic infused 5-FU, and with advantagesin convenience and patient preference,capecitabine should also replace5-FU/leucovorin in combination."High Response RatesPatients in the phase II trial received a2-hour infusion of oxaliplatin 130 mg/m²on day 1, and oral capecitabine 1,000mg/m² bid on days 1 to 15, followed by 7days off. The treatment continued for 11cycles in patients with tumor response orstable disease, and the median number ofcycles was 9.After a minimum follow-up of 24months, XELOX achieved an overall responserate of 55%. "The high responserate was maintained, with all subgroupsachieving a rate of 50% or higher," accordingto one of the co-investigators,Christopher Twelves, MD, University ofLeeds and Bradford, United Kingdom. Incomparison, earlier studies by de Gramontand Goldberg combining 5-FU andoxaliplatin showed an overall responserate of 50% and 38%, respectively.In the XELOX study, the median progression-free survival was 7.7 months andthe median overall survival was 19.5months. The 1-year survival rate was 71%.Patient ProfilesThe study included 96 patients withmetastatic colorectal cancer. Patientsranged in age from 34 years to 79 years,with a median age of 64 years. Eligiblepatients had measurable metastatic colorectalcancer, a Karnofsky performancestatus greater than 70, a life expectancy ofat least 3 months, no prior therapy withoxaliplatin, capecitabine, or irinotecan(CPT-11, Camptosar), and no prior adjuvanttherapy within 6 months of enrollment.Disease characteristics of the patientswere typical of a first-line metastatic colorectalcancer trial: 64% colon tumors,33% rectal tumors, and 3% rectosigmoidtumors. More than half of the patients(54%) had more than one metastatic site.Lung metastases were present in 32% ofpatients and liver metastases in 77%.Twenty-seven percent of patients had receivedprior adjuvant treatment.Capecitabine and oxaliplatin do notoverlap in key toxicities. The safety datawere consistent with prior studies withXELOX, and compare favorably with thesafety profile of FOLFOX4 (fluorouracil,leucovorin, oxaliplatin).Overall, there was a low incidence ofgrade 3/4 treatment-related adverseevents, and only three patients experiencedgrade 3 hand-foot syndrome. Themost common grade 3/4 treatment-relatedadverse events were sensory neuropathy(17%), diarrhea (16%), and nausea/vomiting (13%).Impressive PercentageReceive Full DoseOf particular importance was the factthat 50% of patients received full dosecapecitabine/oxaliplatin throughout theirtreatment-an impressive percentage giventhe long duration of the treatment."XELOX has comparable efficacy andsafety to the FOLFOX regimens in firstlinetreatment of metastatic colorectalcancer, being highly active and safe, whilerequiring far less time of the patient." Dr.Van Cutsem concluded,Ongoing phase III trials are evaluatingXELOX and comparing it to FOLFOX.The objective of these studies is to verifythe ability of capecitabine to replace5-FU/leucovorin as the backbone of advancedcolorectal cancer therapy.