Randomised study of tegafur-uracil plus leucovorin versus capecitabine as first-line therapy in elderly patients with advanced colorectal cancer--TLC study.

BACKGROUND Prospective data on chemotherapy for (frail) elderly patients with advanced colorectal cancer (aCRC) are scant. UFT/leucovorin might be as effective as and less toxic than capecitabine. We firstly randomized both agents in patients >65 years with aCRC not amenable to receive combination chemotherapy. PATIENTS AND METHODS Patients were randomised between first-line oral UFT/leucovorin and capecitabine in a Dutch multicentre trial. Primarily, efficacy and toxicity were determined. Secondary, quality of life (QoL) and abbreviated common geriatric assessment (aCGA) were analysed. RESULTS Sixty-seven patients were randomised with a median age of 77 years and 96% being frail. After interim analysis it was decided to stop recruitment because of low accrual. At a median follow up of 34 months, the median progression-free survival (PFS) and overall survival (OS) were similar for both therapies, being 21 weeks (p=0.17) and 12 months (p=0.83), respectively. The overall response rates were 24% and 21%, respectively. Two patients died of possible treatment related complications in the UFT/leucovorin arm and 3 patients in the capecitabine arm. For UFT/leucovorin significantly less grade 3 or 4 hand/foot syndrome (0 vs 5) was observed. Overall, PFS was related to Charlson-comorbidity index (p=0.049), LDH (p=0.0011) and albumin (p=0.009). OS was related to LDH (p=0.0003), albumin (p=0.0001), QoLC30/CR38 (p=0.041), QoL visual analogue scale (VAS; p=0.016), and GFI (p=0.028). CONCLUSION UFT/leucovorin and capecitabine had similar efficacy and different toxicity profiles in frail elderly patients with aCRC. Baseline serum levels of albumin and LDH, Charlson-comorbidity index, GFI and QoL were prognostic for clinical outcome.