VILLEJUIF, FRANCE-In the first randomized comparison of a schedule of FOLFOX6 (fluorouracil [5-FU], leucovorin, oxaliplatin(Drug information on oxaliplatin) [Eloxatin]) vs standard XELOX (capecitabine [Xeloda]/oxaliplatin) in metatstatic colorectal cancer, XELOX was shown to have a favorable safety profile (abstract 3596). Preliminary Analysis of XELOX Favorable Lead investigator Michel Ducreux, MD, PhD, of Institut Gustave Roussy in Villejuif, France, revealed that the FOLFOX6 regimen is relatively common in France. "If final results of this study confirm the preliminary analyses," the investigators concluded, "XELOX offers benefits to the patient in terms of clinical safety:

• similar rates of diarrhea, nausea, vomiting, fever, and asthenia, but more hand-foot syndrome;
• less paresthesia, neuropathy, and neutropenia."

In this phase III multicenter French trial, the most common clinical adverse events for both regimens were paresthesia, diarrhea, nausea, vomiting, and asthenia (see Table 1). Grade 3/4 clinical adverse events occurred in less than 15% of patients. XELOX led to fewer cases of grade 3/4 paresthesia and neuropathy but more cases of diarrhea, asthenia, and vomiting. One patient in each arm experienced grade 3/4 chest pain, and one toxic death occurred in each arm. Overall, patients in the arm receiving XELOX experienced fewer hematologic adverse events, including neutropenia, thrombocytopenia, anemia, and febrile neutropenia (see Table 2). Among grade 3/4 hematologic adverse events, XELOX was associated with less neutropenia but more thrombocytopenia. Treatment Cycles Vary Of the 177 patients in the study, 91 were randomized to receive XELOX and 86, FOLFOX6. The XELOX regi- men consisted of oral capecitabine(Drug information on capecitabine) (1,000 mg/m² twice daily on days 1 to 14) and oxaliplatin (130 mg/m² via 2- hour infusion on day 1). The FOLFOX6 regimen consisted of 5-FU (400 mg/m² IV bolus on day 1), followed by 2,400 to 3,000 mg/m² as a 46-hour infusion, in addition to leucovorin (400 mg/m²) and oxaliplatin (100 mg/ m² via 2-hour infusion on day 1). The XELOX cycle was 3 weeks long and the FOLFOX6 cycle was 2 weeks long. The median number of cycles completed was 6 (range 1-8) for XELOX and 11 (range 1-12) for FOLFOX6. More than 90% of patients in the study had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Patient characteristics were generally well matched. Eligible patients could have undergone no prior treatment for metastatic disease, although 20% of FOLFOX6 patients and 28% of XELOX patients had undergone previous adjuvant chemotherapy, mostly 5-FU-based therapy. Trial enrollment was expected to be completed in summer 2005.