The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study.
OBJECTIVE
Hand-foot syndrome (HFS) is a common adverse event that can be induced by capecitabine. It is hypothesized that capecitabine (Hoffmann-La Roche Inc.) based chemotherapy can cause overexpression of COX-2 in tumor and healthy tissue, which finally induced HFS in hands and feet. Based on this, we believed that a selected COX-2 inhibitor (celecoxib, Pfizer Pharmaceuticals LLC) could ease HFS. We designed a prospective clinical study to test the hypothesis.


METHODS
From August 2008 to January 2010, 110 patients with stage II/III colorectal cancer who were eligible for adjuvant chemotherapy were enrolled in the study and divided into 4 groups by random, but 9 patients did not finish at least 4 cycles of chemotherapy. There were sixteen patients in capecitabine group, and fifteen patients in capecitabine and celecoxib group. Thirty-four patients were in XELOX (capecitabine plus oxaliplatine) group, and thirty-six patients in XELOX+ celecoxib group. All 101 patients finished chemotherapy and follow-up interviews.


RESULTS
The group that had received capecitabine and celecoxib had a significantly reduced frequency of  >grade 1 hand-foot syndrome (29 vs. 72% P < 0.001), and >grade 2 (11.76% vs. 30% P = 0.024). Five patients experienced grade 3 HFS in capecitabine group and only 1 patient had grade 3 HFS in capecitabine and celecoxib group. There were 5 patients in capecitabine group who refused to go on chemotherapy because of HFS, but there was none in capecitabine and celecoxib group.


CONCLUSIONS
From the result of this study, we could learn that celecoxib could reduce HFS that was induced by capecitabine. So we recommend that celecoxib can be used in capecitabine-based chemotherapy.
Department of Colorectal Surgery, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, People's Republic of China. zhangrx@mail.sys.edu.cn
Rong-Xin
RX
Zhang
Xiao-Jun
XJ
Wu
Shi-Xun
SX
Lu
Zhi-Zhong
ZZ
Pan
De-Sen
DS
Wan
Gong
G
Chen
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005533:Foot Dermatoses / Q000139:chemically induced* / Q000188:drug therapy; D006229:Hand Dermatoses / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011446:Prospective Studies
D000964:Antimetabolites, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil