Capecitabine/Irinotecan Combination Regimens Active as First-Line Treatment of 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.

SAN FRANCISCO-Twophase II trials found capecitabine (Xeloda)active as first-line treatment withirinotecan and well tolerated in patientswith metastatic colorectal cancer,researchers reported in poster presentationsat the GastrointestinalCancers Symposium.Flat-Dose Regimen
Howard A. Burris, MD, Director ofDrug Development at the Sarah CannonCancer Center, Nashville, Tennessee,and his colleagues reportedtheir early results "show that continuousflat-dose capecitabine plus weeklyirinotecan [Camptosar] is a feasibleand active first-line treatment for metastaticcolorectal cancer, achieving diseasecontrol in two-thirds of patients."They said the antitumor activityobserved is similar to that achievedwith irinotecan plus bolus or infusedfluorouracil/leucovorin (5-FU/LV)(abstract 229).In their multicenter study, Dr. Burrisand associates evaluated continuous,flat-dose capecitabine (1,000 mgtwice daily) plus weekly irinotecan inpatients with previously untreatedmetastatic or locally advanced colorectalcancer. They enrolled 62 patients(35 male, 17 female, median age 65years), most of whom had only poorlyor moderately differentiated tumors.Among 49 evaluable patients, objectiveresponses have occurred in 15patients (31%), including unconfirmedresponses in five. Disease wasstabilized in a further 15 patients (31%,unconfirmed in three), yielding a diseasecontrol rate of 61%. Currently,median time to progression is 5.4months, and median overall survivalis 16.7 months, Dr. Burris told ONI.Adverse events were predominantly(90%) mild to moderate and noneoccurred at grade 4 intensity. The mostcommon adverse events were gastrointestinal:diarrhea (60%) and nausea/vomiting (46%), which occurredat grade 3 intensity in 17% and 12%,respectively. Grade 3/4 neutropeniadid not occur. Adverse events led todose modification in 31 patients(60%), but only nine discontinuedstudy treatment. Only 8% of the patientshad grade 1 hand-foot syndrome,which amounted to a littleredness that disappeared with a 2-daybreak from the drug, Dr. Burris said."By giving a virtually nontoxic regimen,"he added, "we're still endingup with a response greater than 30%,"and the pill form of capecitabine simplifiesadministration.XELIRI
Yehuda Z. Patt, MD, chief of gastrointestinaloncology at the Universityof Maryland Greenebaum CancerCenter, reported on results of a multicentertrial that combined 2 weeks ofcapecitabine and 3-weekly irinotecan(XELIRI) as a first-line therapy in thetreatment of metastatic colorectal cancer(abstract 228). For the trial, researchersenrolled 52 patients (29 male,23 female), with a median age of 58years. Most had liver metastases (77%),multiple metastatic sites (73%), andpoorly/moderately differentiated tumors(78%).Patients were treated with IV irinotecan250 mg/m2 on day 1 plus oralcapecitabine 1,000 mg/m2 twice dailyfrom day 1 (PM) until the morning ofday 15, every 21 days, with startingdosereduction to 75% in patients whowere 65 years or older or had renalimpairment. Objective responses wereachieved in 24 patients (46%) andXELIRI demonstrated considerableactivity in poor-risk subgroups, includingthose with Karnofsky performancestatus less than or equal to 80%(33%), with prior neoadjuvant therapy(30%), or age greater than 60 years(41%).Only five patients experiencedgrade 4 adverse events, and grade 3hand-foot syndrome occurred in only6%. Grade 3-4 neutropenia occurredin only 25% of patients and was thereforeless common than reported withthe IFL regimen (incorporating bolus5-FU/LV) or FOLFIRI (infused 5-FU/LV). Most patients (86%) requireddose modification to manage adverseevents, but only 12 patients withdrewbecause of adverse events. There havebeen no treatment-related deaths.The researchers concluded thatXELIRI is a highly active first-line treatmentfor metastatic colorectal cancer,achieving similar efficacy and favorablesafety compared with IFL andFOLFIRI. They noted that XELIRIis also more convenient comparedwith regimens containing infused5-FU/LV.