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

J Geriatr Oncol. 2015 Jul;6(4):307-15. doi: 10.1016/j.jgo.2015.05.004. Epub 2015 Jul 17.

Abstract

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.

Keywords: Advanced colorectal cancer; CGA; Capecitabine; Chemotherapy; Elderly; UFT/leucovorin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Frail Elderly
  • Humans
  • Leucovorin / therapeutic use*
  • Male
  • Prospective Studies
  • Tegafur / therapeutic use*
  • Treatment Outcome
  • Vitamin B Complex / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Vitamin B Complex
  • Tegafur
  • Capecitabine
  • Leucovorin
  • Fluorouracil