ROCHESTER, Minnesota-After disease progression on capecitabine(Drug information on capecitabine) (Xeloda)-based first-line therapy of metastatic colorectal cancer, secondline treatment with one of two capecitabine- based regimens is "effective and tolerable," according to results of a randomized phase II trial (abstract 3534) presented at the 40th Annual Meeting of the American Society of Clinical Oncology. High response rates and effective disease control were seen with both second-line treatments, capecitabine/ irinotecan(Drug information on irinotecan) (Camptosar) (CAPIRI) and capecitabine/oxaliplatin (Eloxatin) (CAPOX), according to lead investigator Axel Grothey, MD, a medical oncologist and Mayo Clinic Foundation Scholar at the Mayo Clinic, Rochester, Minnesota. Phase II Crossover Trial In the phase II trial, patients were randomized to first-line treatment with CAPIRI and CAPOX; after disease progression, they were crossed over to the other treatment. That design is similar to a previous, well-cited trial comparing a FOLFOX (fluorouracil [5-FU], leucovorin [LV], oxaliplatin(Drug information on oxaliplatin))/FOLFIRI (5-FU, LV, irinotecan) sequence to FOLFIRI/FOLFOX. "It's intriguing that capecitabine could replace 5-FU in combination protocols with irinotecan and oxaliplatin," Dr. Grothey said, "but we still do not know this on a phase III level." A total of 161 patients were randomized to receive either CAPIRI or CAPOX on every-3-week cycles. The oral capecitabine dose in both arms was 1,000 mg/m2 twice daily for days 1-14, while IV irinotecan was given at 100 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 were described last year at ASCO: the overall response rates for CAPIRI and CAPOX were 51% and 41%, respectively, with median progression-free survival times of 6.2 and 7.1 months, respectively. Grade 3-4 diarrhea was seen in 13% and 14% of patients, respectively, while patients in the CAPOX arm had more grade 3 handfoot syndrome (4% vs 0) and grade 3- 4 neuropathy (8% vs 2%). Comparable Efficacy A total of 34 patients receiving first-line CAPOX crossed over to CAPIRI following disease progression, while 31 CAPIRI patients crossed over to CAPOX; overall response to second-line therapy was 21% and 13%, respectively, and median progression- free survival time was 5.1 vs 4.3 months. Overall survival time was also similar, at 16.5 months for the CAPOX/CAPIRI sequence, and 18.8 months for CAPIRI/CAPOX. Safety was "predictable and manageable" for both second-line strategies, according to investigators. For CAPOX, the most common grade 3-4 adverse events were leukocytopenia and hyperbilirubinemia, occurring in 13% and 10% of patients, respectively. For CAPIRI, the most common grade 3-4 events included diarrhea and residual neuropathy from first-line CAPOX, both occurring in 11% of patients. These results "do not suggest superior efficacy of either regimen"; accordingly, order of treatment might depend on pretreatment patient characteristics and comorbidities, the researchers said. Ahead to Phase III While the findings are encouraging, Dr. Grothey maintained that "we need definitive results of phase III trials comparing FOLFIRI vs CAPIRI, and FOLFOX vs CAPOX, to make sure that we do not lose efficacy with the capecitabine protocol-that we don't sacrifice efficacy for convenience," Dr. Grothey said. This study served as the basis of an ongoing phase III German AIO (The Association of Medical Oncology of the German Cancer Society) trial comparing CAPOX to infusional 5-FU/ LV and oxaliplatin as first-line therapy for metastatic colorectal cancer. An interim safety analysis of that trial, also presented at ASCO (abstract 3546), suggested the first-line therapies were well tolerated and had comparable toxicity profiles.