title: Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival?
abstract: OBJECTIVE
  COX-2 activation may mediate capecitabine induced toxicities, eg, hand-foot syndrome (HFS) and colorectal cancer progression, both of which may be improved by concurrent celecoxib.
  
  
  METHODS
  From October 2000 to December 2003, 66 patients with metastatic colorectal cancer received concurrent capecitabine at 1000 mg/m/d b.i.d. and celecoxib at 200 mg b.i.d. (XCEL). Twenty-four patients were chemo-naive, 42 patients were second-line; while 34 had XCEL with radiation.
  
  
  RESULTS
  The median duration of XCEL was 7.2 months (range, 1.5-38 months). Ninety percent of Grade 2/3 HFS (17%) occurred after 6 months and incidence of grade 3/4 diarrheas was 8%. The overall response rate was 38% (95% confidence interval [CI], 26-51%), with 11 patients (17%) achieving complete responses and 2 patients (3%) with near complete responses. Six patients (9%) become resectable after sustaining treatment response. The median progression-free survival (PFS) and overall survival (OS) was 8.3 months (95% CI, 7.0-11.0 months) and 22 months (95% CI, 17.8-31.5 months), respectively. Improved median PFS of 14.5 months (P = 0.0001) and OS of 31.5 months (P = 0.005) were noted in patients with normal lactate dehydrogenase (LDH) levels (n = 37) than patients with high levels of LDH (n = 29).
  
  
  CONCLUSIONS
  XCEL integrating radiation may improve response rate and survival and reduce toxicities, notably HFS for patients with metastatic colorectal cancer, leading to a randomized phase III study.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. elin@mdanderson.org
authors.forename: Edward H
authors.initials: EH
authors.lastname: Lin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Crane
authors.forename: Barry
authors.initials: B
authors.lastname: Feig
authors.forename: John
authors.initials: J
authors.lastname: Skibber
authors.forename: Marc
authors.initials: M
authors.lastname: Delcos
authors.forename: Saroj-Raj
authors.initials: SR
authors.lastname: Vadhan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Morris
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ayers
authors.forename: Alicia
authors.initials: A
authors.lastname: Ross
authors.forename: Thomas
authors.initials: T
authors.lastname: Brown
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodriguez-Bigas
authors.forename: Nora
authors.initials: N
authors.lastname: Janjan
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D011720:Pyrazoles / Q000008:administration & dosage; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011720:Pyrazoles; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D000068579:Celecoxib; D005472:Fluorouracil