COX-2 Inhibitors

COX-2 Inhibitors

PEP Topic 
Mucositis
Description 

COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug that directly affects COX-2, an enzyme involved in inflammation and associated pain. The use of COX-2 inhibitors was evaluated in patients with cancer related to the development of palmar-plantar erythrodysesthesia (PPE) skin effects and as a potential treatment for oral mucositis. Celecoxib, a type of COX-2 inhibitor, has also been studied for its impact on symptoms of depression in patients with cancer.

Effectiveness Not Established

Research Evidence Summaries

Lalla, R.V., Choquette, L.E., Curley, K.F., Dowsett, R.J., Feinn, R.S., Hegde, U.P., . . . Peterson, D.E. (2014). Randomized double-blind placebo-controlled trial of celecoxib for oral mucositis in patients receiving radiation therapy for head and neck cancer. Oral Oncology, 50, 1098–1103. 

doi: 10.1016/j.oraloncology.2014.08.001
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Study Purpose:

To investigate the effects of cyclooxygenase-2 (COX-2) inhibition on the severity and morbidity or oral mucositis in patients with head and neck cancer undergoing radiation based on the role of inflammatory pathways in oral mucositis pathogenesis

Intervention Characteristics/Basic Study Process:

Patients were randomized using a one-to-one ratio in blocks of 10 to receive either celecoxib or a placebo. The celecoxib and placebo capsules were identical. The first four patients took 200 mg of celecoxib twice per day beginning five days prior to the first day of radiation therapy and continuing for three days after the conclusion of radiation therapy. Dosing was modified for all subsequent patients to 200 mg of oral celecoxib once per day only on the days of radiation therapy from the first to the last day of therapy. Subsequent patients assigned to the control arm took the placebo once per day for the same duration. Data were collected two to three times per week for the six to seven weeks during which radiation occurred.

Sample Characteristics:

  • N = 40  
  • AVERAGE AGE = 54.6 years 
  • MALES: 32 (80%), FEMALES: 8 (20%)
  • KEY DISEASE CHARACTERISTICS: Head and neck cancer

Setting:

  • SITE: Multi-site    
  • SETTING TYPE: Multiple settings    
  • LOCATION: Hartford Hospital (outpatient setting)

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Elder care, palliative care

Study Design:

Prospective, randomized, double-blinded, placebo-controlled, parallel-arm trial

Measurement Instruments/Methods:

  • Oral Mucositis Assessment Scale (OMAS)
  • World Health Organization (WHO) oral mucositis scale
  • National Cancer Institute's Common Toxicity Criteria (NCI-CTC) Scale version 2
  • Brief Pain Inventory (BPI)
  • Performance Status Scale (PSS)
  • Advanced opioid converter

Results:

There was no difference in oral mucositis severity between the celecoxib and placebo groups (p = .67).

Conclusions:

The use of a COX-2 inhibitor during radiation in patients with head and neck cancer did not reduce the severity of clinical oral mucositis, mouth pain, dietary compromise, or use of opioid analgesics. This study’s power calculation seems to be weak. The dropout and missing data rate (usually 20%) should be added to satisfy the original power calculation. This increases the significant risk of type II error. Without a study with a larger sample size, this practice cannot be recommended.

Limitations:

  • Small sample (< 100)
  • Risk of bias (sample characteristics): This study has a significant discrepancy for gender distribution. The study was predominantly male patients.
  • Other limitations/explanation: The researchers note that because most of the subjects were on high doses of opioids, the small analgesic effect of 200 mg celecoxib daily may not have been enough of a dose to appreciate a response. They do mention that the four subjects that were on higher-dose therapy (celecoxib 200 mg BID) did not discern any effect on oral mucositis.

Nursing Implications:

This is not an effective option for treating radiation-induced mucositis.

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