CAPIRI and CAPOX Comparable as Second-Line Tx for Advanced CRC

March 2, 2005

This special “annual highlights” supplement to Oncology News International (ONI)is a compilation of selected news on important advances in the management ofgastrointestinal cancers over the past year, as reported in ONI. Guest Editor, Dr.James L. Abbruzzese, comments on the reports included herein and discussesdevelopments in the clinical management of GI cancers, with a look at the impactof targeted agents with cytotoxic chemotherapy, first-line and adjuvant therapies foradvanced disease, and the role of statins and COX-2 inhibitors in prevention.

ROCHESTER, Minnesota-Afterdisease progression on capecitabine(Xeloda)-based first-line therapy ofmetastatic colorectal cancer, secondlinetreatment with one of two capecitabine-based regimens is "effective andtolerable," according to results of a randomizedphase II trial (abstract 3534)presented at the 40th Annual Meetingof the American Society of ClinicalOncology.High response rates and effectivedisease control were seen with bothsecond-line treatments, capecitabine/irinotecan (Camptosar) (CAPIRI) andcapecitabine/oxaliplatin (Eloxatin)(CAPOX), according to lead investigatorAxel Grothey, MD, a medical oncologistand Mayo Clinic FoundationScholar at the Mayo Clinic, Rochester,Minnesota.Phase II Crossover TrialIn the phase II trial, patients wererandomized to first-line treatment withCAPIRI and CAPOX; after disease progression,they were crossed over to theother treatment. That design is similarto a previous, well-cited trial comparinga FOLFOX (fluorouracil [5-FU],leucovorin [LV], oxaliplatin)/FOLFIRI(5-FU, LV, irinotecan) sequence toFOLFIRI/FOLFOX."It's intriguing that capecitabinecould replace 5-FU in combinationprotocols with irinotecan and oxaliplatin,"Dr. Grothey said, "but we still donot 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 arms was1,000 mg/m2 twice daily for days 1-14,while IV irinotecan was given at 100mg/m2 on days 1 and 8 (CAPIRI) andIV oxaliplatin was given at 70 mg/m2 ondays 1 and 8 (CAPOX).Results of first-line treatment were described last year at ASCO: the overallresponse rates for CAPIRI and CAPOXwere 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 EfficacyA total of 34 patients receivingfirst-line CAPOX crossed over toCAPIRI following disease progression,while 31 CAPIRI patients crossedover to CAPOX; overall response tosecond-line therapy was 21% and13%, respectively, and median progression-free survival time was 5.1 vs4.3 months. Overall survival time wasalso similar, at 16.5 months for theCAPOX/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 grade3-4 adverse events were leukocytopeniaand hyperbilirubinemia, occurringin 13% and 10% of patients,respectively. For CAPIRI, the mostcommon grade 3-4 events includeddiarrhea and residual neuropathyfrom first-line CAPOX, both occurringin 11% of patients.These results "do not suggest superiorefficacy of either regimen"; accordingly,order of treatment mightdepend on pretreatment patient characteristicsand comorbidities, the researcherssaid.Ahead to Phase IIIWhile 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/LV and oxaliplatin as first-line therapyfor metastatic colorectal cancer.An interim safety analysis of that trial,also presented at ASCO (abstract3546), suggested the first-line therapieswere well tolerated and had comparabletoxicity profiles.