Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort

Our plain-English summary of Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort, by C. Robinson, H. Alfonso, S. Woo, et al (Lung Cancer, 2014).

The study

• Authors: C. Robinson, H. Alfonso, S. Woo, N. Olsen, A.W. Bill Musk, B.W. Robinson, A.K. Nowak, R.A. Lake
• Journal: Lung Cancer
• Published: 2014;86(1):29-34
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma.

Materials And Methods: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site).

Results: Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively.

Conclusion: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In plain English

This study had two parts. First, MexTAg mice, bred to develop mesothelioma after asbestos exposure, were injected with crocidolite asbestos in the abdominal cavity. Their feed contained aspirin at 50 or 250 mg per kg of food (about 6 and 25 mg per kg of body weight daily), or none. Median survival was 33.25, 32.00 and 33.75 weeks for high-aspirin, low-aspirin and control mice, a non-significant difference. High-dose mice showed first signs of disease slightly later than controls (p = 0.049), though the three-group comparison was not significant (p = 0.08); time from diagnosis to endpoint did not differ. Second, 1738 former workers at the Wittenoom crocidolite mine and mill in Western Australia or residents of its township reported their medicines, and 103 later developed mesothelioma. Against non-users, adjusted hazard ratios were 0.56 (95% CI 0.17 to 1.84) for COX-2 inhibitors, 0.83 (0.51 to 1.34) for NSAIDs and 0.46 (0.17 to 1.19) for both. None was statistically significant. The authors concluded that these drugs did not alter mesothelioma development, but said a benefit could not be completely ruled out.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment in transgenic mice combined with an observational study of a human cohort
• Who was studied: MexTAg 299 h transgenic mice. Also 1738 of 2363 participants in the Vitamin A Programme who gave information on medication use. These participants were former workers at the Wittenoom crocidolite mine and mill or former residents of the Wittenoom township, about 20 km from the mine and mill, in Western Australia. They were followed until mesothelioma diagnosis or death, or until 30 June 2012 (average 10.3 years).
• Exposure: Mice received two intraperitoneal injections of 3 mg Wittenoom crocidolite, 1 month apart. Aspirin was mixed into their powdered diet at 50 or 250 mg/kg of food, which the authors estimated as approximately 6 and 25 mg/kg daily intake. In the human cohort, people were exposed to crocidolite at Wittenoom, and the study used their self-reported current use of NSAIDs (aspirin, ibuprofen, naproxen) or COX-2 inhibitors (celecoxib, lumiracoxib, rofecoxib).
• Main results:
  • In mice, median survival was 33.25 weeks (high aspirin), 32.00 weeks (low aspirin) and 33.75 weeks (control), with log rank p = 0.26.
  • In mice, latency (time from asbestos exposure to diagnosis) was slightly longer in the high-dose aspirin group than in controls (t-test p = 0.049). Across all three groups, the difference in latency was not significant (p = 0.08).
  • In mice, time from diagnosis to endpoint did not differ among the three groups (p = 0.92).
  • In the Wittenoom cohort, 103 people were diagnosed with mesothelioma by the end of the study.
  • People taking COX-2 inhibitors (3 of 103 developed mesothelioma) had an adjusted hazard ratio of 0.56 (95% CI 0.17 to 1.84, p = 0.34) compared with non-users. This was not statistically significant.
  • People taking NSAIDs (38 of 565 developed mesothelioma) had an adjusted hazard ratio of 0.83 (95% CI 0.51 to 1.34, p = 0.44) compared with non-users. This was not statistically significant.
  • People using both drug types had mesothelioma in 4.0% (5 of 126), compared with 6.0% (57 of 944) of people using neither. The adjusted hazard ratio was 0.46 (95% CI 0.17 to 1.19, p = 0.11), which was not significant.
  • When measured from first asbestos exposure, the hazard ratios were 0.51 (95% CI 0.16 to 1.68, p = 0.27) for COX-2 inhibitors, 0.87 (0.54 to 1.39, p = 0.55) for NSAIDs and 0.47 (0.18 to 1.24, p = 0.13) for both. None was significant.
• The authors' conclusion: The authors concluded that NSAIDs and COX-2 inhibitors did not alter mesothelioma development. They noted a non-significant trend towards benefit in the human cohort and said a benefit should not be completely ruled out, but that any gain would be moderate in terms of survival.
• Limitations the authors state:
  • The questionnaire gave no information on dose, frequency or duration of drug use.
  • Imprecise drug-use information may have weakened any positive association, so a benefit cannot be excluded.
  • The human data are subject to variation from environmental, lifestyle, dietary and genetic factors, and from imprecise information on drug use and asbestos exposure.
  • The number of people affected was small.
  • The longer latency in aspirin-fed mice may reflect aspirin reducing fluid build-up (ascites) used for diagnosis, rather than an effect on the disease itself.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Incidence, Chronic Inflammation, Mesothelioma, Wittenoom, Crocidolite, Latency, Asbestos Exposure.

Related studies

• Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans — C. Robinson, H. Alfonso, et al. (2014)
• Dietary vitamin D supplementation does not reduce the incidence or severity of asbestos-induced mesothelioma in a mouse model — C. Robinson, S. Woo, et al. (2014)
• The antioxidants vitamins A and E and selenium do not reduce the incidence of asbestos-induced disease in a mouse model of mesothelioma — C. Robinson, S. Woo, et al. (2012)
• MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma — C. Robinson, A. Walsh, et al. (2011)
• The use of wild animal models to detect evidence of environmental contamination by asbestos-like substance — R. Puleio, M.R. Schiavo, et al. (2013)
• Background incidence of mesothelioma: animal and human evidence — E.B. Ilgren, J.C. Wagner (1991)

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