title: Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma.
abstract: BACKGROUND
  The Fédération Francophone de Cancérologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs.
  
  
  METHODS
  QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ≥5 points without any further improvement in QoL score ≥5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event.
  
  
  RESULTS
  From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3-6.2) in Arm A and 6.1 months (5.1-8.5) in Arm B (log-rank p=0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p<0.05).
  
  
  CONCLUSIONS
  The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials.
authors: Biostatistic and Epidemiological Unit (EA 4184) and Clinical Research Platform Qualité de vie et Cancer, Centre Georges François Leclerc Cancer Care Center, Dijon, France. fbonnetain@cgfl.fr
authors: Franck
authors: F
authors: Bonnetain
authors: Laetitia
authors: L
authors: Dahan
authors: Emilie
authors: E
authors: Maillard
authors: Marc
authors: M
authors: Ychou
authors: Emmanuel
authors: E
authors: Mitry
authors: Pascal
authors: P
authors: Hammel
authors: Jean-Louis
authors: JL
authors: Legoux
authors: Philippe
authors: P
authors: Rougier
authors: Laurent
authors: L
authors: Bedenne
authors: Jean-François
authors: JF
authors: Seitz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000523:psychology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004644:Emotions; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D009362:Neoplasm Metastasis; D010146:Pain / Q000209:etiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000523:psychology*; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors