Intra-arterial Infusion of Irinotecan-loaded Drug-eluting Beads (DEBIRI) versus Intravenous Therapy (FOLFIRI) for Hepatic Metastases from Colorectal Cancer: Final Results of a Phase III Study
Anticancer Research, 04/11/2012
Exclusive author commentary
Fiorentini G et al. – This study showed a statistically significant difference between drug–eluting beads preloaded with irinotecan (DEBIRI) and irinotecan, fluorouracil and leucovorin (FOLFIRI) for overall survival (7months), progression–free survival (3months) and quality of life (5 months). In addition, a clinically significant improvement in time to extrahepatic progression (4 months) was observed for DEBIRI, a reversal of the expectation for a regional treatment. This suggests a benefit of DEBIRI treatment over standard chemotherapy and serves to establish the expected difference between these two treatment options for planning future large randomized studies.Methods
- In a multi-institutional study, 74 patients were randomly assigned to receive DEBIRI (36) versus systemic irinotecan, fluorouracil and leucovorin (FOLFIRI, 38).
- The primary end-point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost and influence of molecular markers.
- At 50months, overall survival was significantly longer for patients treated with DEBIRI than for those treated with FOLFIRI (p=0.031, log-rank).
- Median survival was 22 (95% Confidence Interval CI=21-23)months, for DEBIRI and 15 (95% CI=12-18)months for FOLFIRI.
- Progression-free survival was 7 (95% CI=3-11) months in the DEBIRI group compared to 4 (95% CI=3-5)months in the FOLFIRI group and the difference between groups was statistically significant (p=0.006, log-rank).
- Extrahepatic progression had occurred in all patients by the end of the study, at a median time of 13 (95% CI=10-16)months in the DEBIRI group compared to 9 (95% CI 5-13)months in the FOLFIRI group.
- A statistically significant difference between groups was not observed (p=0.064, log-rank).
- The median time for duration of improvement to quality of life was 8 (95% CI=3-13)months in the DEBIRI group and 3 (95% CI=2-4)months in the FOLFIRI group.
- The difference in duration of improvement was statistically significant (p=0.00002, log-rank).
Giammaria Fiorentini (04/13/2012) comments:
The question of survival benefit for chemoembolization has not clearly reported in a randomized trial like ours. Such a trial was unsuccessful attempted from 1997 to 2003 by the National Cancer Institute through the American College of Radiology Imaging Network (ACRIN protocol 6655) and ECOG, in which patients initiated systemic therapy and were then randomized to also receive chemoembolization in the experimental arm or systemic therapy only in the control arm. The rapid evolution of systemic chemotherapy for colon cancer during that period as new drugs were approved resulted in repeated redesign of the trial to avoid obsolescence in the control arm, and the trial was abandoned when a consensus was reached that systemic therapy regimens for this disease were too unstable to serve as a control for a 4- to 5-year survival study. This is the importance of our study: to show a clear advantage of survival in patients treated with chemoembolization compared to systemic chmotherapy