Zhang, R.X., Wu, X.J., Lu, S.X., Pan, Z.Z., Wan, D.S., & Chen, G. (2011). 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. Journal of Cancer Research and Clinical Oncology, 137, 953–957.

Capecitabine is hypothesized to cause overexpression of COX-2 in tumor and healthy tissue, inducing hand-foot syndrome (HFS). This prospective clinical trial will address whether the addition of a COX-2 inhibitor plus capecitabine can decrease or ease HFS.

Patients were randomly assigned to adjuvant treatment with capecitabine plus oxaliplatin or capecitabine alone, with or without celecoxib. The COX-2 inhibitor dose was 200 mg/m² BID in combination with capecitabine for 14 days. Adverse events were monitored continuously during treatment and for 30 days after the last dose of study drug. The intensity of adverse events was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

• The study reported on  a sample of 101 patients with colorectal cancer.
• Patients were aged 18 years or older.
• The sample was 56% male and 43% female.
• Patients were postcurative surgery and eligible for adjuvant chemotherapy with capecitabine-based therapy.

• Single site
• Outpatient
• Republic of China
   

Patients were undergoing the active treatment phase of care.

This was a randomized, prospective phase 2 clinical trial.

HFS was evaluated according to the NCI CTCAE, version 4.0.

• Patients in the capecitabine plus celecoxib group had a significantly reduced frequency of HFS higher than grade 1 (p < 0.001) and grade 2 (p = 0.024) compared to patients in the groups without celecoxib.
• No significant differences existed between groups in grade 3 HFS.

Celecoxib was safe and convenient for patients receiving chemotherapy and reduced the incidence of lower grade HFS.

• The study was a phase 2 trial and was not placebo controlled.
• The study was no blinded.
• Why lower grade HFS would be affected whereas no differences occurred in higher grade HFS between groups is unclear. This raises questions over the reliability of HFS toxicity grading. The authors stated the incidence of HFS in this study was higher than that reported elsewhere, which may have been caused by the fact that they defined grade 1 HFS as any slight pigmentation change.
• Who did the grading was not described.

In the correct population of patients, COX-2 inhibitors can be suggested. Additional research in this area is warranted.