Effect of NSAIDs on the recurrence of nonmelanoma skin cancer

Abstract

Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) against nonmelanoma skin cancers (NMSC). However, little human epidemiological research has been done in this regard. We used data from the Skin Cancer Chemoprevention Study to explore the association of NSAID use and with the risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). 1,805 subjects with a recent history of NMSC were randomized to placebo or 50 mg of daily b-cartene. Participants were asked about their use of over-the-counter and prescription medications at baseline and every 4 months during the trial. Skin follow-up examinations were scheduled annually with a study dermatologist; confirmed lesions were the endpoints in the study. We used a risk set approach to the analysis of grouped times survival data and unconditional logistic regression to compute odds ratios [ORs] for various exposures to NSAIDs. The use of NSAIDs was reported in over 50% of questionnaires. For BCC, NSAIDs exhibited a weak protective effect in crude analyses, which attenuated markedly after adjustment. For SCC, the use of NSAIDs in the year previous to diagnosis reduced the odds by almost 30% (adjusted OR5 0.71, 95% CI 0.48-1.04). When we accounted for frequency of use, results for BCC were not striking, and there were inconsistent suggestions of an inverse association with SCC. There were some indications of a modest, nonsignificant reduction on the number of BCCs and SCCs with NSAID use. Our data suggest a weak and inconsistent chemopreventive effect of NSAIDs on BCC and SCC. ' 2006 Wiley-Liss, Inc.The chemopreventive effect of nonsteroidal antiinflammatory drugs (NSAIDs), particularly aspirin, on nonmelanoma skin cancer (NMSC) has been repeatedly shown in animal [1][2][3][4][5] and in in vitro studies. 6,7 In humans, some experimental studies have reported that topical or oral NSAIDs may lead to regression of skin neoplasms. [8][9][10] Findings from both observational studies [11][12][13][14][15][16][17] and clinical trials 18-20 are consistent with a protective effect of NSAIDs against colorectal neoplasia, but few epidemiological studies have investigated the preventive effects of NSAIDs on risk of nonmelanoma skin cancer, 21,22 the most commonly occurring cancer in the Caucasian population. 23,24 However, results from 1 single-arm, unblinded study and from a randomized trial of topical diclofenac for treatment of actinic keratoses, a well-known precursor of SCC, have been encouraging. 25,26 In the present analysis, we used data from a skin cancer chemoprevention trial, 27 to explore the relationship between NSAID use and the occurrence of nonmelanoma skin cancer, both basal-cell carcinomas (BCC) and squamous-cell carcinomas (SCC). Material and methodsThe Skin Cancer Prevention Study was a randomized, double blind trial of oral b-carotene for the prevention of nonmelanoma skin cancer in patients with a recent history of these tumors. Details of the study design and methods have been described el...

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

“…On average, previous studies reported a higher prevalence of NSAID use. [3][4][5][6][7][8][9][10][11][12][13] This discrepancy is likely attributable to differences in defining ''ever users,'' age and sex distributions, and the source of exposure data (self-reported vs prescription records).…”

“…1,2 Previous studies largely support a protective role of NSAIDs in development of keratinocyte carcinomas, ie, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as malignant melanoma (MM). [3][4][5][6][7][8][9][10][11][12][13] Thus, the results from 1 randomized controlled study indicated a lower risk of keratinocyte carcinomas associated with use of the COX-2 inhibitor celecoxib. 8 However, the previous studies are controversial and are difficult to compare because of differences in outcome measures (eg, inclusion or exclusion of in situ cancers), study design, study populations (eg, high-risk populations vs general populations), and type and measure of NSAID use.…”

“…8 However, the previous studies are controversial and are difficult to compare because of differences in outcome measures (eg, inclusion or exclusion of in situ cancers), study design, study populations (eg, high-risk populations vs general populations), and type and measure of NSAID use. [3][4][5][6][7][8][9][10][11][12][13] Therefore, we conducted a population-based, case-control study using validated registry data to examine whether orally administered aspirin, other nonselective NSAIDs, or COX-2 inhibitors are associated with reduced incidence of SCC, BCC or MM.…”

Photosensitizing Medication Use and Risk of Skin Cancer

“…11) and their potential to increase the risk of UVR-related skin cancers, very few epidemiologic studies have addressed the question of a possible association of photosensitizing medication use with skin cancer (4,(12)(13)(14), and the results of these studies have often been equivocal. Furthermore, skin cancers are not a single entity but different diseases with different sun exposure-related risk factors; for example, early, intermittent overexposure to the sun is thought to be most important for the development of CMM and basal cell carcinoma (BCC; refs.…”

Novel Hedgehog pathway targets against basal cell carcinoma

“…Treatment of sporadic BCCs with topical retinoids such as tazarotene can be successful; however complete tumor regression occurs in less than 50% of BCCs so treated (Bianchi et al, 2004). A retinoid precursor, β-carotene, and other less toxic agents such as non-steroidal anti-inflammatory agents (NSAIDs), do not have a significant effect in lowering BCC risk (Frieling et al, 2000) (Grau et al, 2006). One provocative study has suggested that BCC may also be prevented with a low-fat diet.…”