OBJECTIVES: This study evaluated rates of treatment modifications and reasons for these changes among patients treated with angiogenesis inhibitors in Irish clinical practice. METHODS: Data from medical records were retrospectively reviewed at 3 large oncology centers in Ireland for mRCC patients who were ≥18 years and received sunitinib (N=54), sorafenib (N=9), bevacizumab (N=6), or temsirolimus (N=7) as first-line treatment from January 1, 2005 to August 31, 2010.  Proportions of patients with treatment discontinuation, interruption, or dose change, and reasons for modifications and time to modifications were determined.  RESULTS: Due to small sample sizes in other groups, only results for sunitinib are summarized.  Patients totaling 1.9% had prior cytokine therapy.  Median first-line angiogenesis inhibitor treatment duration for sunitinib was 8.7 months.  A total of 87% of patients treated with first-line sunitinib experienced ≥1 adverse event (AE); 18.5% experienced ≥1 grade 3/4 AE.  70.4% of patients discontinued first-line sunitinib mainly due to progressive disease (38.9%).  AEs were the main reason for treatment interruption among 20 (37%) patients that had an interruption.  A total of 94.4% of patients started treatment on 50 mg QD 4/2 dosing; 33.3% of them were dose reduced to 37.5 mg QD 4/2 with median time to reduction 2.7 months.  Overall, 77.8% of the patients had ≥1 treatment modification.  Adverse events led to treatment modifications in 42.6% of patients.  Among patients who discontinued treatment, 31.6% discontinued within 18 weeks (15.8% within 0-6 weeks, 7.9% in 7-12 weeks, and 7.9% in 13-18 weeks).  Among patients who discontinued treatment within 18 weeks, 66.7% discontinued due to AEs. CONCLUSIONS: Over three-quarters of sunitinib patients experienced treatment modifications, more than half due to AEs.  About 24% of treatment discontinuations occurred within the first 2 cycles.  This real-world practice study suggests that treatment tolerability is a challenge for physicians in the clinical care of mRCC patients.