Celebrex (celecoxib) might be effective against a pre-stage of cervical cancer — but only if patients produce high levels of a cancer-related growth factor, according to a recently completed Phase 2 trial (NCT00081263).
Screening for the growth factor, called VEGF (vascular endothelial growth factor), might, therefore, be needed to identify patients that would benefit from treatment with Celebrex, the researchers suggest.
The study, “A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia: The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study,” was led by researchers at the Medical College of Wisconsin. The work was published in the journal Gynecologic Oncology.
Cervical intraepithelial neoplasia 3, or CIN 3, is the scientific name of the final stage of cell changes in the cervix that can lead to cancer if left untreated. The most common treatment for CIN 3 involves various surgical techniques to remove the affected area. This type of surgery can impact a woman’s ability to get pregnant, or increase her risk of premature delivery.
Since this CIN 3 is often found in women of childbearing age, researchers are on the constant lookout for nonsurgical options.
Celebrex is a drug that blocks an enzyme called COX-2, and is approved for treating various pain conditions. While COX-2 is well-known for its role in inflammation and pain, researchers know that some of the factors produced by the enzyme are involved in cancer development.
The Phase 2 trial enrolled 130 patients who were randomized to receive either 400 mg of Celebrex once daily or a placebo. The treatment continued for 14 to 18 weeks, and neither patients nor study staff were aware of the treatment assignment — called a double-blind study setup.
Analyses showed that histologic regression — the reduction of the affected area as assessed by microscopic evaluation — was not statistically different between the groups. Among Celebrex-treated patients, 40% responded to the drug with reduced cell changes. In the placebo group, the proportion of patients who responded was 34.1%.
An analysis of the drug concentration in the blood of patients revealed a very high spread. Celebrex is taken orally, and since patients kept a diary of their drug intake and returned all unused tablets, researchers could conclude that not all patients adhered to the prescribed treatment.
But when they analyzed responses according to how much drug a patient had in their blood, there was no difference in treatment effects between those with high and low Celebrex blood levels.
However, when researchers weighed in patients’ blood serum levels of VEGF, another picture emerged. Among those with low VEGF levels, there was again no difference between Celebrex and placebo-treated patients. But high VEGF was linked to a response. Among Celebrex-treated patients with high VEGF, 47.3% responded to the treatment, while in those taking a placebo, a shrinkage of the affected area was only seen in 14.3%.
The researchers, therefore, suggest that exploring how VEGF impacts cancer development and treatment response should be done in future trials.