Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials.

Journal article

PURPOSE: Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age > or = 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients. RESULTS: Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and > or = 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable. CONCLUSION: Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.

Authors: Folprecht, G; Seymour, M; Saltz, L; Douillard, J; Hecker, H

• Publication status: Published
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• Volume: 26
• Issue: 9
• Pages: 1443-1451
• Publication date: 2008-03-01
• DOI: 10.1200/jco.2007.14.0509
• EISSN: 1527-7755
• ISSN: 0732-183X
• Language: English
• Keywords: Age Factors; Disease-Free Survival; Neoplasm Staging; Colorectal Neoplasms; Treatment Outcome; Female; Confounding Factors (Epidemiology); Male; Logistic Models; Odds Ratio; Leucovorin; Aged; Kaplan-Meier Estimate; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic; Proportional Hazards Models; Humans; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Aged, 80 and over; Camptothecin