Confirmed responses were significantly higher for the FUFOX arm (see Table), with combined complete and partial response rates more than double that of the Mayo arm.
Dr. Grothey noted that grade 3-4 hematologic toxicities were less frequent and less severe with FUFOX (neutropenia, 23.4% vs 6.7%, P = .006). Among nonhematologic toxicities, nausea was more common with FUFOX (11.0% vs 3.2%, P = .023), as was diarrhea (27.15 vs 16.9%, P = .063).
After 8 cycles (oxaliplatin cumulative dose 1,200 mg/m2), grade 3-4 sensory neuropathies, a known effect with accumulating oxali-platin doses, had occurred in 17% of patients receiving FUFOX (1.7% grade 4). Only 5.1% discontinued FUFOX due to sensory neuropathies.
For 60-day all-cause mortality, Dr. Grothey reported that there were no deaths due to early progression in the FUFOX arm, compared with 6 deaths (4.8%) for the Mayo regimen. There were four toxic deaths (3.2%) in the Mayo arm and one (0.9%) in the FUFOX arm. Overall, there was one death in the FUFOX arm and 11 in the Mayo arm (8.9% vs 0.9%, P = .0057).
Treatment discontinuations due to adverse events were more common in the FUFOX arm (25.4% vs 4.0%, P < .0001). However, death (8.9% vs 1.7%, P = .02) and progressive disease (71.0% vs 51.7%, P = .0024) were significantly more common reasons for discontinuation in the Mayo arm. Complete response with secondary surgery accounted for more discontinuations in the FUFOX arm (5.9% vs 1.6%, not significant).
Dr. Grothey pointed out that many patients received salvage therapies in the further course of disease, such that 54.2% of Mayo patients and 74.8% of FUFOX patients had received both oxaliplatin(Drug information on oxaliplatin) and irinotecan(Drug information on irinotecan). "Efficient salvage therapies likely contributed to the long median survival in both treatment arms, supporting the strategy of making all active drugs available to all patients," Dr. Grothey said.
He also showed that in recent trials from 2000 to 2002, as the percentage of patients receiving three drugs has increased from 5% to 75% in the current study, median overall survival has increased from 14.8 months (Saltz) to 21.4 months (Grothey).