Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival?
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.
Lin
Edward H
EH
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. elin@mdanderson.org
Curley
Steven A
SA
Crane
Christopher C
CC
Feig
Barry
B
Skibber
John
J
Delcos
Marc
M
Vadhan
Saroj-Raj
SR
Morris
Jeffrey
J
Ayers
Gregory D
GD
Ross
Alicia
A
Brown
Thomas
T
Rodriguez-Bigas
Miguel A
MA
Janjan
Nora
N
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
D000964:Antimetabolites, Antineoplastic; D011720:Pyrazoles; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D000068579:Celecoxib; D005472:Fluorouracil