Oral Capecitabine Is Attractive Alternative to Continuous- Infusion Regimens

BIRMINGHAM, ALABAMA-"Capecitabine can replace continuousinfusion in regimens to treat colorectalcancer," Scott Cole, MD, and colleaguesat the University of Alabamaat Birmingham concluded after reviewingdata on 3,224 patients in phaseI or II studies (abstract 3591). Thestudies were published or availablefrom 1997 to 2004 from the AmericanSociety of Clinical Oncology, the EuropeanSociety for Medical Oncology,and the European Cancer Conference.The safety and efficacy of capecitabine(Xeloda)-based regimens werecompared with those of continuousinfusionfluorouracil (5-FU)-basedregimens, such as FOLFOX (5-FU, leucovorin,oxaliplatin [Eloxatin]) andFOLFIRI (5-FU, leucovorin, irinotecan[Camptosar]). Treatment couldhave been first line or second line andadministered alone or with radiationtherapy, oxaliplatin, or irinotecan.The studies included 1,409 patientstaking capecitabine and 1,815 patientsreceiving 5-FU. The mean age was 62years (range, 18-88 years). An averageof 61% of patients per study had anEastern Cooperative Oncology Group(ECOG) performance status of 0."Our conclusions are limited bythe lack of randomized controlled trialsdirectly comparing capecitabinebasedtherapies with continuous-in-fusion 5-FU-based therapies for thetreatment of colorectal cancer," theinvestigators acknowledged. "Nonetheless,these comparisons have shownthat capecitabine therapies, as monotherapyor combination regimens,provide the following advantages":Advantages

• Capecitabine offers a superiortoxicity profile and at least equivalentresponse rates, time to progression,and survival compared with continuous-infusion treatment when usedalone or in combination with otheragents or radiation therapy in colorectalcancer (first-line, adjuvant,neoadjuvant);
• Capecitabine has demonstrateda better toxicity profile than regimensbased on continuous-infusion5-FU, except for a higher incidence ofhand-foot syndrome, which is manageableby treatment delay and dosereduction as appropriate.
• Using oral dosing may lead tosuperior medical resource utilization.

In background information, theinvestigators noted that although "thelow level of myelosuppression associatedwith continuous infusion makesit an attractive regimen for combiningwith other agents," continuousinfusiontherapies "require an indwellingcatheter, which can lead toinfections and the need for ancillarycare, potentially raising costs and reducingpatient quality of life."

Efficacy and Safety

Overall response rates were similarfor patients taking oral capecitabineand those receiving intravenous continuousinfusion 5-FU, 34% vs 39%(overall response rate odds ratio,0.7917; 95% confidence interval [CI],0.6784 to 0.9239;

P

= .999). Averagesurvival figures were similar: 14.2months for capecitabine and 14.9months for intravenous continuousinfusion5-FU (see Table 1).

Safety was assessed by determiningthe proportion of patients who experiencedgrade 3/4 adverse events (seeTable 2). The reviewers found thatgrade 3/4 hematologic toxicity wasmore frequent in patients on intravenouscontinuous-infusion 5-FU thanin patients on capecitabine (16.31%vs 3.40%,

P

< .0001). Hand-foot syndromewas more frequent in patientsreceiving capecitabine (9.30% vs6.34%,

P

< .999).Capecitabine was associated with asignificantly lower incidence of grade3/4 neutropenia (4.79% vs 27.7%),leading to significantly less grade 3/4neutropenic fevers (1.16% vs 7.72%).Although thromboses were observedin 8% of patients receiving intravenouscontinuous-infusion 5-FU, nonewas reported for patients takingcapecitabine.