Standard first-line therapy for metastatic colorectal cancer in North America is weekly bolus irinotecan, 5-fluorouracil and leucovorin (IFL).

The North Central Cancer Treatment Group (NCCTG) reported in Intergroup trial N9741 that 4.5% of patients receiving IFL died within 60 days of starting therapy. Investigators were concerned that this represented an excess mortality for patients receiving IFL.

However, investigators found it difficult to quantify the significance of this mortality rate since previous trials did not measure 60-day all cause mortality. Instead, drug related deaths were measured within 30 days of the end of therapy.

Furthermore, it is not known how 60-day mortality rates in clinical trials would compare to mortality rates in real world clinical practice.

To gain more information, investigators assessed 60-day all cause mortality for patients receiving IFL in community practices in the United States. Community practices were studied to determine whether practicing oncologists gave lower starting doses than the current recommendation to avoid toxicity. Investigators conducted this evaluation as part of a safety summary for the FDA.

Investigators at each site evaluated up to 10 consecutive patients treated in the first 4 months of 2001. They compared the 60-day all cause mortality in this group of 240 community practice patients with the 225 patients enrolled in the phase III registration study for IFL (Saltz et al., N Engl J Med. 2000; 343: 905-14).

They found a 60-day all cause mortality rate of 1.3% in the community practice group. This was lower than the rate reported in N9741 (4.5%) and in the Saltz study (6.7%).

The low risk of early mortality in community practice may relate to irinotecan dose reductions according to patient characteristics. Approximately 30% of patients received less than complete starting doses; most of those patients had poor performance status.

(abstract #530)