Celecoxib before surgery: is it safe?

This study evaluated the safety of low dose celecoxib treatment (400 mg/day) for patients with locally advanced rectal cancer.

Locally advanced rectal cancer means the cancer has grown from the rectum (the lowest part of the large bowel) into surrounding tissues and organs. The treatment strategy can include: surgery to remove the cancer, pre-surgery chemotherapy and radiotherapy, or pre-surgery radiotherapy alone. The pre-surgery treatments can help to shrink the tumor and improve the chances of successful surgical removal.

Cyclooxygenase-2 is a protein produced by cells which can help tumors grow, and increased levels have been linked to worse outcomes for patients. It is therefore possible that decreasing the amount of cyclooxygenase-2 could improve patient outcome. The drug celecoxib (Celebrex) can inhibit cyclooxygenase-2 and has the potential to help treat patients with rectal cancer. However, celecoxib can have bad side effects including heart problems, so the dose given to patients requires careful consideration.

53 patients (age 26 to 76) with stage II or III rectal cancer were included in the study. Celecoxib (400 mg/day) was given from days 1 to 65. All patients were treated with radiotherapy throughout the study. Additional chemotherapy consisted of tegafur–uracil (Uftoral) and  leucovorin  (folinate) on days 1-30 and 38-65. Surgery was undertaken on day 70 (47 of the patients).

81% of patients experienced a reduction in tumor size, or a reduction in the degree of lymph node involvement.13% of patients achieved a complete response (complete disappearance of signs of symptoms of cancer). 77% of those with low-rectal tumors achieved sphincter preservation (the ring of muscle surrounding the anal canal remained unaffected by surgery).

Cyclooxygenase-2 was measured in tumor samples taken before and after treatment. 77% of patients had high cyclooxygenase-2 levels before treatment. The pre-surgery treatment significantly decreased the amount of cyclooxygenase-2. Where cyclooxygenase-2 levels remained high after treatment it was linked to increased mortality in patients. 

The treatment strategy resulted in some mild to moderate adverse effects. The most common adverse effects included: rash due to the radiation (67%), fatigue (66%), diarrhea (60%), and altered hemoglobin (a blood protein responsible for carrying oxygen) (59%). Less than 4% of patients experienced any severe adverse effects.

The authors concluded that celecoxib can be safely combined with pre-surgery chemotherapy and radiotherapy for rectal cancer. 

This is a small study and would need to be repeated.