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. 1992 May;65(5):737–743. doi: 10.1038/bjc.1992.156

The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial.

A M Arnold 1, G P Browman 1, M N Levine 1, T D'Souza 1, B Johnstone 1, P Skingley 1, L Turner-Smith 1, R Cayco 1, L Booker 1, M Newhouse 1, et al.
PMCID: PMC1977389  PMID: 1586601

Abstract

Laboratory studies, and one previous uncontrolled trial, have suggested that retinoids may reverse bronchial atypia, a putatively premalignant condition. Sputum sampling is a simple, non-invasive method of assessing atypia. Smokers with at least a 15 pack-year history were screened for sputum atypia. One hundred and fifty subjects' were randomised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months. Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels. The outcomes assessed were, improvements in sputum atypia and toxicity. At baseline there was no significant difference between the two groups with respect to gender, smoking history or extent of atypia. Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months. Compliance as measured by pill counts and etretinate levels was high. Eighty-six per cent of subjects on etretinate took 90% or more of their prescribed medication and etretinate was detected in 245 of 264 samples. By contrast etretinate was detected in only six of 266 samples in the control group and probably did not represent true contamination. After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms. Toxicity was mild in both groups with considerable placebo effect noted. Etretinate, at the dose used in this study, had no impact on sputum atypia as detected by sputum sampling.

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Selected References

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  1. AUERBACH O., PETRICK T. G., STOUT A. P., STATSINGER A. L., MUEHSAM G. E., FORMAN J. B., GERE J. B. The anatomical approach to the study of smoking and bronchogenic carcinoma; a preliminary report of forty-one cases. Cancer. 1956 Jan-Feb;9(1):76–83. doi: 10.1002/1097-0142(195601/02)9:1<76::aid-cncr2820090106>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  2. Arnold A. M., Browman G. P., Johnstone B., Skingley P., Booker L., Levine M. N. Chemoprevention for lung cancer--evidence for a high degree of compliance. Cancer Detect Prev. 1990;14(5):521–525. [PubMed] [Google Scholar]
  3. Arnold A., Johnstone B., Stoskopf B., Skingley P., Browman G., Levine M., Hryniuk W. Recruitment for an efficacy study in chemoprevention--the Concerned Smoker Study. Prev Med. 1989 Sep;18(5):700–710. doi: 10.1016/0091-7435(89)90041-8. [DOI] [PubMed] [Google Scholar]
  4. BERGMAN A. B., WERNER R. J. Failure of children to receive penicillin by mouth. N Engl J Med. 1963 Jun 13;268:1334–1338. doi: 10.1056/NEJM196306132682404. [DOI] [PubMed] [Google Scholar]
  5. Band P. R., Deschamps M., Israël L. Retinoid chemoprevention timing and dose intensity. Cancer Invest. 1989;7(2):205–210. doi: 10.3109/07357908909038286. [DOI] [PubMed] [Google Scholar]
  6. Boone C. W., Kelloff G. J., Malone W. E. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. Cancer Res. 1990 Jan 1;50(1):2–9. [PubMed] [Google Scholar]
  7. Browman G. P., Arnold A., Booker L., Johnstone B., Skingley P., Levine M. N. Etretinate blood levels in monitoring of compliance and contamination in a chemoprevention trial. J Natl Cancer Inst. 1989 May 10;81(10):795–798. doi: 10.1093/jnci/81.10.795. [DOI] [PubMed] [Google Scholar]
  8. Browman G. P., Arnold A., Levine M. N., D'Souza T., Turner-Smith L. M., Cayco R., Johnstone B., Birse R. Use of screening phase data to evaluate observer variation of sputum cytodiagnosis as an outcome measure in a chemoprevention trial. Cancer Res. 1990 Feb 15;50(4):1216–1219. [PubMed] [Google Scholar]
  9. Crocker T. T., Sanders L. L. Influence of vitamin A and 3,7-dimethyl-2,6-octadienal (citral) on the effect of benzo(a)pyrene on hamster trachea in organ culture. Cancer Res. 1970 May;30(5):1312–1318. [PubMed] [Google Scholar]
  10. Greenberg E. R., Baron J. A., Stukel T. A., Stevens M. M., Mandel J. S., Spencer S. K., Elias P. M., Lowe N., Nierenberg D. W., Bayrd G. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med. 1990 Sep 20;323(12):789–795. doi: 10.1056/NEJM199009203231204. [DOI] [PubMed] [Google Scholar]
  11. Heimburger D. C., Alexander C. B., Birch R., Butterworth C. E., Jr, Bailey W. C., Krumdieck C. L. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. JAMA. 1988 Mar 11;259(10):1525–1530. [PubMed] [Google Scholar]
  12. Hong W. K., Bromer R. Chemotherapy in head and neck cancer. N Engl J Med. 1983 Jan 13;308(2):75–79. doi: 10.1056/NEJM198301133080204. [DOI] [PubMed] [Google Scholar]
  13. Hong W. K., Endicott J., Itri L. M., Doos W., Batsakis J. G., Bell R., Fofonoff S., Byers R., Atkinson E. N., Vaughan C. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986 Dec 11;315(24):1501–1505. doi: 10.1056/NEJM198612113152401. [DOI] [PubMed] [Google Scholar]
  14. Hong W. K., Lippman S. M., Itri L. M., Karp D. D., Lee J. S., Byers R. M., Schantz S. P., Kramer A. M., Lotan R., Peters L. J. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990 Sep 20;323(12):795–801. doi: 10.1056/NEJM199009203231205. [DOI] [PubMed] [Google Scholar]
  15. Koch H. F. Biochemical treatment of precancerous oral lesions: the effectiveness of various analogues of retinoic acid. J Maxillofac Surg. 1978 Feb;6(1):59–63. doi: 10.1016/s0301-0503(78)80069-1. [DOI] [PubMed] [Google Scholar]
  16. Lippman S. M., Kessler J. F., Meyskens F. L., Jr Retinoids as preventive and therapeutic anticancer agents (Part I). Cancer Treat Rep. 1987 Apr;71(4):391–405. [PubMed] [Google Scholar]
  17. Lippman S. M., Lee J. S., Lotan R., Hittelman W., Wargovich M. J., Hong W. K. Biomarkers as intermediate end points in chemoprevention trials. J Natl Cancer Inst. 1990 Apr 4;82(7):555–560. doi: 10.1093/jnci/82.7.555. [DOI] [PubMed] [Google Scholar]
  18. Mathe G., Gouveia J., Hercend T., Gros F., Dorval T., Hazon J., Misset J. L., Schwarzenberg L., Ribaud P., Lemaigre G. Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment. Cancer Detect Prev. 1982;5(4):461–466. [PubMed] [Google Scholar]
  19. McClean S. W., Ruddel M. E., Gross E. G., DeGiovanna J. J., Peck G. L. Liquid-chromatographic assay for retinol (vitamin A) and retinol analogs in therapeutic trials. Clin Chem. 1982 Apr;28(4 Pt 1):693–696. [PubMed] [Google Scholar]
  20. Meyskens F. L., Jr Coming of age--the chemoprevention of cancer. N Engl J Med. 1990 Sep 20;323(12):825–827. doi: 10.1056/NEJM199009203231210. [DOI] [PubMed] [Google Scholar]
  21. Saccomanno G., Archer V. E., Auerbach O., Saunders R. P., Brennan L. M. Development of carcinoma of the lung as reflected in exfoliated cells. Cancer. 1974 Jan;33(1):256–270. doi: 10.1002/1097-0142(197401)33:1<256::aid-cncr2820330139>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  22. Saccomanno G., Moran P. G., Schmidt R., Hartshorn D. F., Brian D. A., Dreher W. H., Sowada B. J. Effects of 13-CIS retinoids on premalignant and malignant cells of lung origin. Acta Cytol. 1982 Jan-Feb;26(1):78–85. [PubMed] [Google Scholar]
  23. Saccomanno G., Saunders R. P., Archer V. E., Auerbach O., Kuschner M., Beckler P. A. Cancer of the lung: the cytology of sputum prior to the development of carcinoma. Acta Cytol. 1965 Nov-Dec;9(6):413–423. [PubMed] [Google Scholar]
  24. Saffiotti U., Montesano R., Sellakumar A. R., Borg S. A. Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer. 1967 May;20(5):857–864. doi: 10.1002/1097-0142(1967)20:5<857::aid-cncr2820200545>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  25. Sporn M. B., Roberts A. B., Roche N. S., Kagechika H., Shudo K. Mechanism of action of retinoids. J Am Acad Dermatol. 1986 Oct;15(4 Pt 2):756–764. doi: 10.1016/s0190-9622(86)70231-4. [DOI] [PubMed] [Google Scholar]
  26. Willett W. C., Polk B. F., Underwood B. A., Stampfer M. J., Pressel S., Rosner B., Taylor J. O., Schneider K., Hames C. G. Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J Med. 1984 Feb 16;310(7):430–434. doi: 10.1056/NEJM198402163100705. [DOI] [PubMed] [Google Scholar]
  27. Zelen M. Are primary cancer prevention trials feasible? J Natl Cancer Inst. 1988 Nov 16;80(18):1442–1444. doi: 10.1093/jnci/80.18.1442. [DOI] [PubMed] [Google Scholar]

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