Randomized Trial of Two Induction Chemotherapy Regimens in Metastatic Colorectal Cancer: An Updated Analysis

In a randomized trial with a median follow-up of 18.4 months, 6 months of induction chemotherapy with a three-drug regimen comprising 5-fluorouracil (by continuous infusion)-leucovorin, irinotecan, and oxaliplatin (FOLFOXIRI) demonstrated statistically significant improvements in response rate, radi...

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Published in:JNCI : Journal of the National Cancer Institute 2011-01, Vol.103 (1), p.21-30
Main Authors: MASI, Gianluca, VASILE, Enrico, FABBRI, Maria Agnese, PUGLISI, Martina, TRENTA, Patrizia, GRANETTO, Cristina, CHIARA, Silvana, FIORETTO, Luisa, ALLEGRINI, Giacomo, CRINO, Lucio, ANDREUCCETTI, Michele, FALCONE, Alfredo, LOUPAKIS, Fotios, CUPINI, Samanta, FORNARO, Lorenzo, BALDI, Giacomo, SALVATORE, Lisa, CREMOLINI, Chiara, STASI, Irene, BRUNETTI, Isa
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Camptothecin - administration & dosage
Camptothecin - analogs & derivatives
Chemotherapy
Clinical outcomes
Clinical trials
Colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Disease-Free Survival
Female
Fluorouracil - administration & dosage
Follow-Up Studies
Humans
Infusions, Intravenous
Kaplan-Meier Estimate
Leucovorin - administration & dosage
Male
Medical sciences
Middle Aged
Monoclonal antibodies
Multivariate Analysis
Neoplasm Staging
Organoplatinum Compounds - administration & dosage
Pharmacology. Drug treatments
Proportional Hazards Models
Remission Induction
Sample Size
Toxins
Treatment Outcome
Tumors
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Summary:In a randomized trial with a median follow-up of 18.4 months, 6 months of induction chemotherapy with a three-drug regimen comprising 5-fluorouracil (by continuous infusion)-leucovorin, irinotecan, and oxaliplatin (FOLFOXIRI) demonstrated statistically significant improvements in response rate, radical surgical resection of metastases, progression-free survival, and overall survival compared with 6 months of induction chemotherapy with fluorouracil-leucovorin and irinotecan (FOLFIRI). From November 14, 2001, to April 22, 2005, we enrolled 244 patients with metastatic colorectal cancer. To evaluate if the superiority of FOLFOXIRI is maintained in the long term, we updated the overall and progression-free survival data to include events that occurred up to February 12, 2009, with a median follow-up of 60.6 months. We performed a subgroup and a risk-stratified analysis to examine whether outcomes differed in specific patient subgroups, and we analyzed the results of treatment after progression. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. FOLFOXIRI demonstrated statistically significant improvements in median progression-free survival (9.8 vs 6.8 months, HR for progression = 0.59, 95% CI = 0.45 to 0.76, P < .001) and median overall survival (23.4 vs 16.7 months, HR for death = 0.74, 95% CI = 0.56 to 0.96, P = .026) with a 5-year survival rate of 15% (95% CI = 9% to 23%) vs 8% (95% CI = 4% to 14%). The improvements in progression-free survival and, to a lesser extent, in overall survival were evident even when the analysis excluded patients who received radical resection of metastases. With regard to the risk-stratified analysis, FOLFOXIRI results in longer progression-free survival and overall survival than FOLFIRI in all risk subgroups. Six months of induction chemotherapy with FOLFOXIRI is associated with a clinically significant improvement in the long-term outcome compared with FOLFIRI with an absolute benefit in survival at 5 years of 7%.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/djq456