title: Clinical benefit response in pancreatic cancer trials revisited.
abstract: OBJECTIVE
  Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception.
  
  
  METHODS
  CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs).
  
  
  RESULTS
  The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals.
  
  
  CONCLUSIONS
  CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.forename: Daniel
authors.initials: D
authors.lastname: Dietrich
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: György
authors.initials: G
authors.lastname: Bodoky
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.forename: Richard
authors.initials: R
authors.lastname: Herrmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000069287:Capecitabine; D015984:Causality; D015897:Comorbidity; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004358:Drug Therapy / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D017567:Karnofsky Performance Status; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010146:Pain / Q000401:mortality / Q000517:prevention & control* / Q000523:psychology*; D010166:Palliative Care; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D011788:Quality of Life / Q000523:psychology*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine