Basal Cell Carcinoma Chemoprevention with Nonsteroidal Anti-inflammatory Drugs in Genetically Predisposed PTCH1+/− Humans and Mice

Abstract

In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study of their efficacy in preventing the more common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition of cyclooxygenase (COX) enzymes in the skin of Ptch1 +/− mice. We then assessed the effects of celecoxib on the development of BCCs in a 3-year, double-blinded, randomized clinical trial in 60 (PTCH1 +/− ) patients with the basal cell nevus syndrome. In Ptch1 +/− mice, genetic deletion of COX1 or COX2 robustly decreased (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the human trial, we detected a trend for oral celecoxib reducing BCC burden in all subjects (P = 0.069). Considering only the 60% of patients with less severe disease (<15 BCCs at study entry), celecoxib significantly reduced BCC number and burden: subjects receiving placebo had a 50% increase in BCC burden per year, whereas subjects in the celecoxib group had a 20% increase (P difference = 0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1 +/− mice and had a significant anti-BCC effect in humans with less severe disease. Cancer Prev Res; 3(1); 25-34. ©2010 AACR.

Oral acetylsalicylic acid and prevalence of actinic keratosis

“…44 Coincidentally, a controlled double-blind prospective study observed 20% less new BCC lesions in carriers of basal cell nevus syndrome after having used celecoxib for three years. 45 Although the inhibition of COX-2 by ASA occurs in a dose-dependent ratio, the oral use of just 81mg daily reduces significantly the prostaglandin E2 levels in the distal colonic mucosa justifying that clinic effect under low dosages, as detected in our sample. 46 Besides, COX-2 independent antineoplastic mechanisms have already been proposed for ASA, such as the activation of the kappa beta nuclear factor (NF-κβ) and stimulus to the expression of DNA repair proteins such as: hMLH1 and hPMS2.…”

Anti-Proliferative Effects of Piroxicam and Nimesulide on A431 Human Squamous Carcinoma Cell Line

“…In a study by Tang et al it was shown that celecoxib (a selective COX-2 inhibitor) decreased BCC tumor development in mice and humans (39). In another study, Agarwal et al found a 50% decrease in A431 cell viability at a con- In our research, we found that the IC 50 value of nimesulide was significantly lower than piroxicam in 24 and 72 hours treatment.…”

Guidelines of care for the management of basal cell carcinoma

“…131,132 Although there is evidence that oral celecoxib makes NMSC in general, and BCC in particular, less likely in patients with previous NMSC, the potential benefits should be weighed against the significant risk for a cardiovascular event that is associated with this medication. 133,134 The dietary supplements b-carotene and selenium have also been studied, and are not recommended for reducing risk for BCC or cSCC in patients with a history of BCC. Several RCTs have shown no protective benefit against NMSC associated with either b-carotene or selenium.…”

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