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

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 >= 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 >= 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.