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. PATIENTS AND 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.