549P - Gender and chemotherapy-related toxicity in colon cancer: an analysis of the PETACC-3 trial conducted by the EORTC GI-group

Abstract

Drug metabolism is genetically determined. Gender is one of the factors responsible for the large interpatient variability in the dose-effect relationship of cytotoxics. Comparative data on the effect of gender on chemotherapy (CT)-related toxicity are lacking in colon cancer. This is a retrospective analysis of data from the PETACC-3 trial: 2974 pts (55.7% men (m) and 44.3% women (f)) with stage II and III colon cancer were treated with adjuvant 5-fluorouracil/leucovorin alone (5FU/LV) or with irinotecan (FOLFIRI). Primary aim was to compare CT-related toxicity (according to NCIC-CTCG) in m and f. Clinical and hematologic adverse events (AEs) rates and frequency of dose reductions in m and f were compared by Fisher's exact test; survival outcomes by log-rank test. Subgroup analyses were performed according to age (<50, 50-65, ≥65) and treatment. P-values are 2-sided. No multiple testing adjustments were done. Higher rates of all grade nausea (61.8 vs 53.7%, p < .0001), vomiting (32.5 vs 24.5%, p < .0001), alopecia (41.7 vs 26.0%, p < .0001) and more all grade leucopenia, anemia and neutropenia (p < .0001) were observed in f compared with m. Differences in these AEs between f and m were found significant (p < 0.05) in both arms and in all age groups except for nausea and neutropenia in age <50. Additionally, in the FOLFIRI arm, f had greater risks of stomatitis (40.6 vs 30%, p < .0001), cramping (24.2 vs 16.4%, p = 0.0002), cholinergic syndrome (18.3 vs 12.9%, p = 0.0045) and lethargy (48.9 vs 38.2%, p < 0.0001) as well as more grade 3-4 neutropenia (37.3 vs 21.1%, p < .0001) than m. There was no significant difference in febrile neutropenia between m and f. Dose reductions were more frequent in f (25.9% vs 16.8%, p < .0001) but the mean cumulative doses of CT (mg/m2) were not significantly different between m and f. There were no significant differences in PFS or OS. In this trial, women demonstrated significantly greater rates of various hematological and non-hematological AEs, especially under treatment with FOLFIRI. Thus, AEs need to be reported according to gender in future clinical trials. Further data investigating the relationship between gender and CT efficacy and toxicity is required.