Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Jan;71(1):120–123. doi: 10.1038/bjc.1995.24

Decrease in pulmonary function during bleomycin-containing combination chemotherapy for testicular cancer: not only a bleomycin effect.

S Sleijfer 1, T W van der Mark 1, H Schraffordt Koops 1, N H Mulder 1
PMCID: PMC2033457  PMID: 7529523

Abstract

This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This enabled us to establish whether effects other than those due to bleomycin determined the detrimental effects of BEP on lung function assessments. Slow inspiratory vital capacity (VC), the transfer factor of the lungs for carbon monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm), the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs for carbon monoxide per unit alveolar volume (KCO) were determined before and at 3 week intervals during chemotherapy. Both groups, similar in terms of factors that may influence pulmonary function, showed during therapy a significant decrease in TLCO compared with the pretreatment value. Only at the end of the therapy was a significant difference in TLCO between both groups observed. Dm diminished also significantly in both groups during treatment, but differences between both groups were not seen. VC and Vc decreased in patients receiving BEP but remained constant during treatment with EP. It can be concluded that the Dm, KCO, and the widely used TLCO are not suitable parameters to monitor specifically pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However, VC and Vc appear to be proper lung function assessments which reflect specifically alterations induced by bleomycin.

Full text

PDF
120

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson I. Y., Bowden D. H. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol. 1974 Nov;77(2):185–197. [PMC free article] [PubMed] [Google Scholar]
  2. Adoue D., Arlet P. Bleomycin and Raynaud's phenomenon. Ann Intern Med. 1984 May;100(5):770–770. doi: 10.7326/0003-4819-100-5-770_2. [DOI] [PubMed] [Google Scholar]
  3. BLAKEMORE W. S., FORSTER R. E., MORTON J. W., OGILVIE C. M. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957 Jan;36(1 Pt 1):1–17. doi: 10.1172/JCI103402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Comis R. L. Bleomycin pulmonary toxicity: current status and future directions. Semin Oncol. 1992 Apr;19(2 Suppl 5):64–70. [PubMed] [Google Scholar]
  5. Comis R. L., Kuppinger M. S., Ginsberg S. J., Crooke S. T., Gilbert R., Auchincloss J. H., Prestayko A. W. Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients. Cancer Res. 1979 Dec;39(12):5076–5080. [PubMed] [Google Scholar]
  6. Dearnaley D. P., Horwich A., A'Hern R., Nicholls J., Jay G., Hendry W. F., Peckham M. J. Combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for metastatic testicular teratoma: long-term follow-up. Eur J Cancer. 1991;27(6):684–691. doi: 10.1016/0277-5379(91)90166-b. [DOI] [PubMed] [Google Scholar]
  7. Doll D. C., Yarbro J. W. Vascular toxicity associated with antineoplastic agents. Semin Oncol. 1992 Oct;19(5):580–596. [PubMed] [Google Scholar]
  8. Ginsberg S. J., Comis R. L. The pulmonary toxicity of antineoplastic agents. Semin Oncol. 1982 Mar;9(1):34–51. [PubMed] [Google Scholar]
  9. Hansen S. W., Groth S., Sørensen P. G., Rossing N., Rørth M. Enhanced pulmonary toxicity in smokers with germ-cell cancer treated with cis-platinum, vinblastine and bleomycin: a long-term follow-up. Eur J Cancer Clin Oncol. 1989 Apr;25(4):733–736. doi: 10.1016/0277-5379(89)90211-3. [DOI] [PubMed] [Google Scholar]
  10. Joselson R., Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Pathol. 1983 Jan;14(1):88–91. doi: 10.1016/s0046-8177(83)80052-5. [DOI] [PubMed] [Google Scholar]
  11. Jules-Elysee K., White D. A. Bleomycin-induced pulmonary toxicity. Clin Chest Med. 1990 Mar;11(1):1–20. [PubMed] [Google Scholar]
  12. Khalil N., Bereznay O., Sporn M., Greenberg A. H. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med. 1989 Sep 1;170(3):727–737. doi: 10.1084/jem.170.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Krogh M. The diffusion of gases through the lungs of man. J Physiol. 1915 May 12;49(4):271–300. doi: 10.1113/jphysiol.1915.sp001710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levi J. A., Raghavan D., Harvey V., Thompson D., Sandeman T., Gill G., Stuart-Harris R., Snyder R., Byrne M., Kerestes Z. The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group. J Clin Oncol. 1993 Jul;11(7):1300–1305. doi: 10.1200/JCO.1993.11.7.1300. [DOI] [PubMed] [Google Scholar]
  15. Luursema P. B., Star-Kroesen M. A., van der Mark T. W., Sleyfer D. T., Koops H. S., Peset R. Bleomycin-induced changes in the carbon monoxide transfer factor of the lungs and its components. Am Rev Respir Dis. 1983 Nov;128(5):880–883. doi: 10.1164/arrd.1983.128.5.880. [DOI] [PubMed] [Google Scholar]
  16. Moseley P. L., Hemken C., Hunninghake G. W. Augmentation of fibroblast proliferation by bleomycin. J Clin Invest. 1986 Nov;78(5):1150–1154. doi: 10.1172/JCI112695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Onuma T., Holland J. F., Masuda H., Waligunda J. A., Goldberg G. A. Microbiological assay of bleomycin: inactivation, tissue distribution, and clearance. Cancer. 1974 May;33(5):1230–1238. doi: 10.1002/1097-0142(197405)33:5<1230::aid-cncr2820330507>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  18. Osanto S., Bukman A., Van Hoek F., Sterk P. J., De Laat J. A., Hermans J. Long-term effects of chemotherapy in patients with testicular cancer. J Clin Oncol. 1992 Apr;10(4):574–579. doi: 10.1200/JCO.1992.10.4.574. [DOI] [PubMed] [Google Scholar]
  19. Otsuka K., Murota S. I., Mori Y. Stimulatory effect of bleomycin on the hyaluronic acid synthetase in cultured fibroblasts. Biochem Pharmacol. 1978;27(11):1551–1554. doi: 10.1016/0006-2952(78)90484-7. [DOI] [PubMed] [Google Scholar]
  20. ROUGHTON F. J., FORSTER R. E. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J Appl Physiol. 1957 Sep;11(2):290–302. doi: 10.1152/jappl.1957.11.2.290. [DOI] [PubMed] [Google Scholar]
  21. Samuels B. L., Vogelzang N. J., Kennedy B. J. Severe vascular toxicity associated with vinblastine, bleomycin, and cisplatin chemotherapy. Cancer Chemother Pharmacol. 1987;19(3):253–256. doi: 10.1007/BF00252982. [DOI] [PubMed] [Google Scholar]
  22. Sørensen P. G., Rossing N., Rørth M. Carbon monoxide diffusing capacity: a reliable indicator of bleomycin-induced pulmonary toxicity. Eur J Respir Dis. 1985 May;66(5):333–340. [PubMed] [Google Scholar]
  23. Van Barneveld P. W., Sleijfer D. T., van der Mark T. W., Mulder N. H., Koops H. S., Sluiter H. J., Peset R. Natural course of bleomycin-induced pneumonitis. A follow-up study. Am Rev Respir Dis. 1987 Jan;135(1):48–51. doi: 10.1164/arrd.1987.135.1.48. [DOI] [PubMed] [Google Scholar]
  24. Van Barneveld P. W., van der Mark T. W., Sleijfer D. T., Mulder N. H., Koops H. S., Sluiter H. J., Peset R. Predictive factors for bleomycin-induced pneumonitis. Am Rev Respir Dis. 1984 Dec;130(6):1078–1081. doi: 10.1164/arrd.1984.130.6.1078. [DOI] [PubMed] [Google Scholar]
  25. Vogelzang N. J., Bosl G. J., Johnson K., Kennedy B. J. Raynaud's phenomenon: a common toxicity after combination chemotherapy for testicular cancer. Ann Intern Med. 1981 Sep;95(3):288–292. doi: 10.7326/0003-4819-95-3-288. [DOI] [PubMed] [Google Scholar]
  26. Williams S. D., Birch R., Einhorn L. H., Irwin L., Greco F. A., Loehrer P. J. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987 Jun 4;316(23):1435–1440. doi: 10.1056/NEJM198706043162302. [DOI] [PubMed] [Google Scholar]
  27. Wolkowicz J., Sturgeon J., Rawji M., Chan C. K. Bleomycin-induced pulmonary function abnormalities. Chest. 1992 Jan;101(1):97–101. doi: 10.1378/chest.101.1.97. [DOI] [PubMed] [Google Scholar]
  28. Zimmerman M. S., Ruckdeschel J. C., Hussain M. Chemotherapy-induced interstitial pneumonitis during treatment of small cell anaplastic lung cancer. J Clin Oncol. 1984 May;2(5):396–405. doi: 10.1200/JCO.1984.2.5.396. [DOI] [PubMed] [Google Scholar]
  29. van Barneveld P. W., Veenstra G., Sleijfer D. T., van der Mark T. W., Mulder N. H., Schraffordt Koops H., Sluiter H. J., Peset R. Changes in pulmonary function during and after bleomycin treatment in patients with testicular carcinoma. Cancer Chemother Pharmacol. 1985;14(2):168–171. doi: 10.1007/BF00434359. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES