Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer.

Background: The relevance of oncology trial results in clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients with advanced age and poor performance status, patients typically excluded from clinical trials. Methods: A retrospective chart review was performed including all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy (FOLFIRI, IFL, XELIRI, irinotecan monotherapy) from January 2004 to September 2006 at our institution. The toxicity rates of these irinotecan regimens in clinical practice were quantified and subsequently compared to those published in corresponding phase III clinical trials. The primary endpoint was incidence of grade 3/4 diarrhea. Results: A total of 203 patients were included in the study. The rates of grade 3/4 diarrhea for FOLFIRI, IFL, XELIRI and irinotecan monotherapy were 10%, 15%, 17% and 21%, respectively. These compared to 10%, 23%, 20% and 31% in clinical trials for each respective regimen. When only patients meeting the trial performance status and age criteria were included, the rates of grade 3/4 diarrhea in our study were 11%, 20%, 19% and 26%, respectively. Conclusion: Overall, the toxicity rates of FOLFIRI and irinotecan monotherapy, when used in non-trial patients, are not statistically different from those quoted in published clinical trials.