Celecoxib May Lower Risk of Some Skin Ca

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” said Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than do sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham. “There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10-40 actinic keratoses (AKs), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with NSAIDs, although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, and between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, Dr. Elmets said. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared with placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction compared to placebo-treated controls,” he said.

If the two types of lesions are considered separately, celecoxib treatment led to a 58% reduction in squamous cell carcinoma (SCC), and a 62% reduction in basal cell carcinoma (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study. We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than the placebo group.”

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

The data are “very compelling,” commented Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2-5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results. Her study found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. A previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100:967-71).

Celecoxib's lack of effect on AKs is a puzzling result, she added. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

Finally, patients in the COX-2 study were allowed to take cardioprotective doses of aspirin—an important factor that the analysis did not adjust for, she pointed out. “Even low-dose aspirin inhibits COX, and it could just be that the people in the treatment arm were much more likely to be on aspirin as well.”

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” said Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than do sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham. “There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10-40 actinic keratoses (AKs), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with NSAIDs, although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, and between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, Dr. Elmets said. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared with placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction compared to placebo-treated controls,” he said.

If the two types of lesions are considered separately, celecoxib treatment led to a 58% reduction in squamous cell carcinoma (SCC), and a 62% reduction in basal cell carcinoma (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study. We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than the placebo group.”

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

The data are “very compelling,” commented Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2-5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results. Her study found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. A previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100:967-71).

Celecoxib's lack of effect on AKs is a puzzling result, she added. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

Finally, patients in the COX-2 study were allowed to take cardioprotective doses of aspirin—an important factor that the analysis did not adjust for, she pointed out. “Even low-dose aspirin inhibits COX, and it could just be that the people in the treatment arm were much more likely to be on aspirin as well.”

MONTREAL — A twice-daily dose of celecoxib given over a period of 9 months was associated with a 60% reduction in the incidence of nonmelanoma skin cancer, according to the results of a new study.

“Inhibition of COX-2 is an effective means of limiting the development of cutaneous squamous and basal cell carcinomas in humans,” said Dr. Craig Elmets at the annual meeting of the Society for Investigative Dermatology.

The findings suggest that pharmaceutical agents such as celecoxib may offer greater protection against skin cancer than do sunscreens, which are only “modestly effective,” said Dr. Elmets, professor and chair of the department of dermatology and director of the Skin Disease Research Center at the University of Alabama, Birmingham. “There's only about a 35% reduction in squamous cell carcinomas when sunscreens are used on a regular basis over a 5-year period of time, and there's no reduction in basal cell carcinomas.”

The multicenter, randomized, placebo-controlled study was funded by the National Cancer Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, with additional funding from Pfizer through a contractual agreement with the National Institutes of Health, he said. Dr. Elmets did not disclose any personal conflicts of interest.

The study enrolled 238 patients with nonmelanoma skin cancers from eight U.S. centers. The mean age of the patients was 65 years, most were male, and virtually all were white.

“The study was terminated somewhat early because of concerns of cardiovascular effects due to another COX-2 inhibitor,” he noted.

Subjects in the study had Fitzpatrick skin types I-III, extensive actinic damage with 10-40 actinic keratoses (AKs), and a prior histologic diagnosis of either AK or nonmelanoma skin cancer. Subjects were excluded if they required treatment with NSAIDs, although cardioprotective doses of aspirin were allowed.

At entry, patients had a mean number of 22 AKs, and between 2.1 and 2.5 nonmelanoma skin cancers, he said.

Patients were randomized to either placebo or celecoxib 200 mg twice daily, which is the approved dosage for arthritis, Dr. Elmets said. “We were concerned about cardiovascular abnormalities and GI abnormalities, and if anything there was a bias towards patients in the celecoxib group having a prior history of that.”

A comparison of the number of AKs at baseline and completion showed a lack of effect of celecoxib, compared with placebo, he noted. However, the development of new cutaneous basal and squamous cell carcinomas was much reduced. “We were delighted to find that celecoxib was quite effective, with a 58% reduction compared to placebo-treated controls,” he said.

If the two types of lesions are considered separately, celecoxib treatment led to a 58% reduction in squamous cell carcinoma (SCC), and a 62% reduction in basal cell carcinoma (BCC).

“The difference between the [placebo and treated] groups started to become apparent quite rapidly, at 3 months, and persisted throughout the study. We were concerned that there might be one or two outliers that were skewing the results, so rather than looking at the total number of skin cancers, we also looked at the number of individuals who developed BCC or SCC or both. Again we found that patients with celecoxib had fewer BCCs and SCCs than the placebo group.”

There were no differences in adverse events including cardiovascular adverse events between the two groups, Dr. Elmets reported. During the question period, he acknowledged that there were higher blood pressures reported in the treatment group.

The data are “very compelling,” commented Dr. Maryam Asgari of Kaiser Permanente in Oakland, Calif., in an interview. But she suggested perhaps the study was too short to have such dramatic conclusions. “I know that typically for most cancers you would need a study to last 2-5 years before you would expect to measure an effect,” she said. Similarly, adverse events from COX-2 inhibitors would likely need longer to develop.

Dr. Asgari said her research in the same field has produced the opposite results. Her study found no protective effect for all NSAIDs—both selective and nonselective COX inhibitors—on the incidence of squamous cell carcinoma. A previous paper published by her group also found no protective effect of these drugs on melanomas (J. Natl. Cancer Inst. 2008;100:967-71).

Celecoxib's lack of effect on AKs is a puzzling result, she added. “You would think that if COX-2 inhibitors are working to prevent new cancers from arising that they would also have a pretty dramatic effect on actinic keratoses because they both share the same pathway.”

Finally, patients in the COX-2 study were allowed to take cardioprotective doses of aspirin—an important factor that the analysis did not adjust for, she pointed out. “Even low-dose aspirin inhibits COX, and it could just be that the people in the treatment arm were much more likely to be on aspirin as well.”