The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.
ROCHESTER, Minnesota-Afterdisease progression on capecitabine(Xeloda)-based first-line therapyof metastatic colorectal cancer, second-line treatment with one of twocapecitabine-based regimens is "effectiveand tolerable," according to resultsof a randomized phase II trial(abstract 3534).High response rates and effectivedisease control were seen with bothsecond-line treatments, capecitabine/irinotecan (CPT-11, Camptosar)(CAPIRI) and capecitabine/oxaliplatin(Eloxatin) (CAPOX), accordingto lead investigator Axel Grothey, MD,a medical oncologist and Mayo ClinicFoundation Scholar at the Mayo Clinic,Rochester, Minnesota.Phase II Crossover Trial
In the phase II trial, patients wererandomized to first-line treatmentwith CAPIRI and CAPOX; after diseaseprogression, they were crossedover to the other treatment. That de-sign is similar to a previous, well-citedtrial comparing a FOLFOX (fluorouracil[5-FU], leucovorin [LV], oxaliplatin)/FOLFIRI (5-FU, LV, irinotecan)sequence to FOLFIRI/FOLFOX."It's intriguing that capecitabinecould replace 5-FU in combinationprotocols with irinotecan and oxaliplatin,"Dr. Grothey said, "but we stilldo not know this on a phase III level."A total of 161 patients were randomizedto receive either CAPIRI orCAPOX on every-3-week cycles. Theoral capecitabine dose in both armswas 1,000 mg/m2 twice daily for days1-14, while IV irinotecan was given at100 mg/m2 on days 1 and 8 (CAPIRI)and IV oxaliplatin was given at 70 mg/m2 on days 1 and 8 (CAPOX).Results of first-line treatment weredescribed last year at ASCO: the overallresponse rates for CAPIRI andCAPOX were 51% and 41%, respectively,with median progression-freesurvival times of 6.2 and 7.1 months,respectively. Grade 3/4 diarrhea wasseen in 13% and 14% of patients, respectively,while patients in theCAPOX arm had more grade 3 handfootsyndrome (4% vs 0) and grade 3/4 neuropathy (8% vs 2%).Comparable Efficacy
A total of 34 patients receiving firstlineCAPOX crossed over to CAPIRIfollowing disease progression, while31 CAPIRI patients crossed over toCAPOX; overall response to secondlinetherapy was 21% and 13%, respectively,and median progressionfreesurvival time was 5.1 vs 4.3months. Overall survival time was alsosimilar, at 16.5 months for the CAPOX/CAPIRI sequence, and 18.8months for CAPIRI/CAPOX.Safety was "predictable and manageable"for both second-line strategies,according to investigators. ForCAPOX, the most common grade 3/4adverse events were leukocytopeniaand hyperbilirubinemia, occurring in13% and 10% of patients, respectively.For CAPIRI, the most commongrade 3/4 events included diarrheaand residual neuropathy from firstlineCAPOX, both occurring in 11%of patients.These results "do not suggest superiorefficacy of either regimen"; ac-cordingly, order of treatment mightdepend on pretreatment patient characteristicsand comorbidities, the researcherssaid.Ahead to Phase III
While the findings are encouraging,Dr. Grothey maintained that "weneed definitive results of phase III trialscomparing FOLFIRI vs CAPIRI,and FOLFOX vs CAPOX, to makesure that we do not lose efficacy withthe capecitabine protocol-that wedon't sacrifice efficacy for convenience,"Dr. Grothey said.This study served as the basis of anongoing phase III German AIO (TheAssociation of Medical Oncology ofthe German Cancer Society) trial comparingCAPOX to infusional 5-FU/LVand oxaliplatin as first-line therapyfor metastatic colorectal cancer. Aninterim safety analysis of that trial,also presented at ASCO (abstract3546), suggested the first-line therapieswere well tolerated and had comparabletoxicity profiles. Efficacy resultswill be presented at the EuropeanSociety of Medical Oncology Meeting,to be held in Vienna, Austria,from October 29 through November2, 2004.