3555 Background: Tumor-activated capecitabine (Xeloda) has superior response rates and equivalent progression-free and overall survival compared with bolus 5-FU/LV in first-line MCRC, with favorable safety and fewer hospitalizations. This safety advantage is confirmed in the adjuvant setting, where improved safety is also seen in older patients. XELOX is safe and active in first-line MCRC and could also be suitable for older patients. Methods: In this post-hoc analysis of mature safety data in older vs younger patients, 96 patients with MCRC received first-line XELOX: oxaliplatin 130mg/m2 i.v. day 1 followed by oral capecitabine 1,000mg/m2 twice daily, evening day 1–morning day 15, every 3 weeks. All patients are evaluable: 64% male; median age 64 years (34–79); 52 younger patients (<65 years), 44 older patients (≥65 years); median KPS 100 (80–100). Primary tumor: 64% colon; 33% rectal; 3% both. Metastases: 54% >1 metastatic site; 77% liver, 38% lymph nodes, 32% lung. Prior adjuvant fluoropyrimidines: 28%. Results: Patients received a median nine cycles of XELOX. Safety profiles are similar in younger and older patients (table). The incidence of dose reductions and withdrawals for adverse events was similar. The activity of XELOX was also similar in both groups, response rates: 58% (95% CI, 43–71; younger) vs 52% (95% CI, 37–68; older). Conclusions: XELOX has a favorable safety profile with no clinically relevant differences between younger and older patients. Antitumor activity is preserved in older vs younger patients. These results imply that up-front dose reductions are not required when XELOX is prescribed in older patients. Ongoing phase II/III trials are prospectively evaluating XELOX in this population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche; Sanofi Roche Roche