title: Randomised study of tegafur-uracil plus leucovorin versus capecitabine as first-line therapy in elderly patients with advanced colorectal cancer--TLC study.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leiden University Medical Center, Department of Clinical Oncology, Leiden, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
authors.affiliation: The Netherlands Cancer Institute, Department of Statistics, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Polee
authors.affiliation: Departments of Internal Medicine, Amstelland Hospital, Amstelveen, The Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: van Groeningen
authors.affiliation: Department of Internal Medicine, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: Beeker
authors.affiliation: Department of Internal Medicine, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Erdkamp
authors.affiliation: Department of Medical Oncology, Bronovo Hospital, The Hague, The Netherlands.
authors.forename: Nir
authors.initials: N
authors.lastname: Weijl
authors.affiliation: Department of Internal Medicine, Zaans Medical Centre, Zaanstad, The Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: van Bochove
authors.affiliation: Department of Internal Medicine, Ommelander Hospital, Delfzijl, The Netherlands.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Erjavec
authors.affiliation: Leiden University Medical Center, Department of Clinical Oncology, Leiden, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
authors.affiliation: Leiden University Medical Center, Department of Medical Decision Making, Leiden, The Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stiggelbout
authors.affiliation: Leiden University Medical Center, Department of Clinical Oncology, Leiden, The Netherlands.
authors.forename: Hans W R
authors.initials: HW
authors.lastname: Nortier
authors.affiliation: Leiden University Medical Center, Department of Clinical Oncology, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D016330:Frail Elderly; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D005641:Tegafur; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: Advanced colorectal cancer; CGA; Capecitabine; Chemotherapy; Elderly; UFT/leucovorin