Revisiting bleomycin from pathophysiology to safe clinical use

Critical Reviews in Oncology/Hematology

Volumn 87, Issue 1, 2013, Pages 90-100

  Froudarakis, Marios ^a   Hatzimichael, Eleftheria ^b,c,d   Kyriazopoulou, Lydia ^b   Lagos, Konstantinos ^b   Pappas, Periklis ^c   Tzakos, Andreas G ^c   Karavasilis, Vasilis ^e   Daliani, Danai ^f   Papandreou, Christos ^f   Briasoulis, Evangelos ^b,c  

^a DEMOCRITUS UNIVERSITY OF THRACE   (Greece)

^b UNIVERSITY HOSPITAL OF IOANNINA   (Greece)

^c UNIVERSITY OF IOANNINA   (Greece)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

^e ARISTOTLE UNIVERSITY MEDICAL SCHOOL   (Greece)

^f UNIVERSITY OF THESSALY   (Greece)

Author keywords

Bleomycin; Hodgkin's Lymphoma; Lung injury; Safe clinical use; Testicular germ cell tumour; Therapeutics; Toxicity

Indexed keywords

BLEOMYCIN; BRENTUXIMAB VEDOTIN; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DACARBAZINE; DOXORUBICIN; ETOPOSIDE; GRANULOCYTE COLONY STIMULATING FACTOR; PREDNISONE; PROCARBAZINE; VINBLASTINE; VINCRISTINE;

CANCER CHEMOTHERAPY; COUGHING; CYANOSIS; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG INDUCED DISEASE; DRUG STRUCTURE; DRUG USE; DYSPNEA; FEBRILE NEUTROPENIA; FEVER; GERM CELL TUMOR; HODGKIN DISEASE; HUMAN; LUNG INJURY; LUNG TOXICITY; MORBIDITY; MORTALITY; NONHUMAN; PATHOPHYSIOLOGY; PERCUSSION; PHARMACOGENOMICS; PLEURA DISEASE; PLEURAL PAIN; PRACTICE GUIDELINE; REVIEW; SIDE EFFECT; SPUTUM; TACHYPNEA; TESTIS TUMOR; THORAX PAIN;

ANTIBIOTICS, ANTINEOPLASTIC; BLEOMYCIN; HUMANS; INCIDENCE; LUNG INJURY; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS;

EID: 84878555771     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2012.12.003     Document Type: Review

References (88)

1. 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. New England Journal of Medicine 1987, 316:1435-1440.
2. Duggan D.B., Petroni G.R., Johnson J.L., Glick J.H., Fisher R.I., Connors J.M., et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. Journal of Clinical Oncology 2003, 21:607-614.
3. Sleijfer S. Bleomycin-induced pneumonitis. Chest 2001, 120:617-624.
4. Briasoulis E., Pavlidis N. Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy. Oncologist 2001, 6:153-161.
5. O'Sullivan J.M., Huddart R.A., Norman A.R., Nicholls J., Dearnaley D.P., Horwich A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Annals of Oncology 2003, 14:91-96.
6. Martin W.G., Ristow K.M., Habermann T.M., Colgan J.P., Witzig T.E., Ansell S.M. Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma. Journal of Clinical Oncology 2005, 23:7614-7620.
7. Sausville E.A., Stein R.W., Peisach J., Horwitz S.B. Properties and products of the degradation of DNA by bleomycin and iron(II). Biochemistry 1978, 17:2746-2754.
8. Dorr R.T. Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics. Seminars in Oncology 1992, 19:3-8.
9. Umezawa H., Maeda K., Takeuchi T., Okami Y. New antibiotics, bleomycin A and B. Journal of Antibiotics (Tokyo) 1966, 19:200-209.
10. Twentyman P.R. Bleomycin - mode of action with particular reference to the cell cycle. Pharmacology & Therapeutics 1983, 23:417-441.
11. Bromme D., Rossi A.B., Smeekens S.P., Anderson D.C., Payan D.G. Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization. Biochemistry 1996, 35:6706-6714.
12. Sebti S.M., Jani J.P., Mistry J.S., Gorelik E., Lazo J.S. Metabolic inactivation: a mechanism of human tumor resistance to bleomycin. Cancer Research 1991, 51:227-232.
13. Sanz G., Mir L., Jacquemin-Sablon A. Bleomycin resistance in mammalian cells expressing a genetic suppressor element derived from the SRPK1 gene. Cancer Research 2002, 62:4453-4458.
14. Alberts D.S., Chen H.S., Liu R., Himmelstein K.J., Mayersohn M., Perrier D., et al. Bleomycin pharmacokinetics in man. I. Intravenous administration. Cancer Chemotherapy and Pharmacology 1978, 1:177-181.
15. Hall S.W., Strong J.E., Broughton A., Frazier M.L., Benjamin R.S. Bleomycin clinical pharmacology by radioimmunoassay. Cancer Chemotherapy and Pharmacology 1982, 9:22-25.
16. Hay J., Shahzeidi S., Laurent G. Mechanisms of bleomycin-induced lung damage. Archives of Toxicology 1991, 65:81-94.
17. Adamson I.Y., Bowden D.H. Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung. American Journal of Pathology 1979, 96:531-544.
18. Moseley P.L. Augmentation of bleomycin-induced DNA damage in intact cells. American Journal of Physiology 1989, 257:C882-C887.
19. Hay J.G., Haslam P.L., Dewar A., Addis B., Turner-Warwick M., Laurent G.J. Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats. Thorax 1987, 42:374-382.
20. Hoshino T., Okamoto M., Sakazaki Y., Kato S., Young H.A., Aizawa H. Role of proinflammatory cytokines IL-18 and IL-1beta in bleomycin-induced lung injury in humans and mice. American Journal of Respiratory Cell and Molecular Biology 2009, 41:661-670.
21. Sonnenberg G.F., Fouser L.A., Artis D. Functional biology of the IL-22-IL-22R pathway in regulating immunity and inflammation at barrier surfaces. Advances in Immunology 2010, 107:1-29.
22. Saito F., Tasaka S., Inoue K., Miyamoto K., Nakano Y., Ogawa Y., et al. Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice. American Journal of Respiratory Cell and Molecular Biology 2008, 38:566-571.
23. Scheule R.K., Perkins R.C., Hamilton R., Holian A. Bleomycin stimulation of cytokine secretion by the human alveolar macrophage. American Journal of Physiology 1992, 262:L386-L391.
24. Kuwano K., Hagimoto N., Kawasaki M., Yatomi T., Nakamura N., Nagata S., et al. Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis. Journal of Clinical Investigation 1999, 104:13-19.
25. Schmidt R., Ruppert C., Markart P., Lubke N., Ermert L., Weissmann N., et al. Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis. Toxicology and Applied Pharmacology 2004, 195:218-231.
26. Reiser K.M., Tryka A.F., Lindenschmidt R.C., Last J.A., Witschi H.R. Changes in collagen cross-linking in bleomycin-induced pulmonary fibrosis. Journal of Biochemical Toxicology 1986, 1:83-91.
27. Bonner J.C. Mesenchymal cell survival in airway and interstitial pulmonary fibrosis. Fibrogenesis Tissue Repair 2010, 3:15.
28. Van Barneveld P.W., van der Mark T.W., Sleijfer D.T., Mulder N.H., Koops H.S., Sluiter H.J., et al. Predictive factors for bleomycin-induced pneumonitis. American Review of Respiratory Disease 1984, 130:1078-1081.
29. Jules-Elysee K., White D.A. Bleomycin-induced pulmonary toxicity. Clinics in Chest Medicine 1990, 11:1-20.
30. Comis R.L. Bleomycin pulmonary toxicity: current status and future directions. Seminars in Oncology 1992, 19:64-70.
31. Blum R.H., Carter S.K., Agre K. A clinical review of bleomycin - a new antineoplastic agent. Cancer 1973, 31:903-914.
32. Bokemeyer C. Bleomycin in testicular cancer: will pharmacogenomics improve treatment regimens. Journal of Clinical Oncology 2008, 26:1783-1785.
33. de Haas E.C., Zwart N., Meijer C., Nuver J., Boezen H.M., Suurmeijer A.J., et al. Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer. Journal of Clinical Oncology 2008, 26:1817-1823.
34. Samuels M.L., Johnson D.E., Holoye P.Y., Lanzotti V.J. Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy. JAMA 1976, 235:1117-1120.
35. Collis C.H. Lung damage from cytotoxic drugs. Cancer Chemotherapy and Pharmacology 1980, 4:17-27.
36. Wilson K.S., Worth A., Richards A.G., Ford H.S. Low-dose bleomycin lung. Medical and Pediatric Oncology 1982, 10:283-288.
37. Bauer K.A., Skarin A.T., Balikian J.P., Garnick M.B., Rosenthal D.S., Canellos G.P. Pulmonary complications associated with combination chemotherapy programs containing bleomycin. American Journal of Medicine 1983, 74:557-563.
38. Simpson A.B., Paul J., Graham J., Kaye S.B. Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours. British Journal of Cancer 1998, 78:1061-1066.
39. Batist G. Reversible low-dose bleomycin lung disease. JAMA 1980, 243:331.
40. McLeod B.F., Lawrence H.J., Smith D.W., Vogt P.J., Gandara D.R. Fatal bleomycin toxicity from a low cumulative dose in a patient with renal insufficiency. Cancer 1987, 60:2617-2620.
41. De Lena M., Guzzon A., Monfardini S., Bonadonna G. Clinical, radiologic, and histopathologic studies on pulmonary toxicity induced by treatment with bleomycin (NSC-125066). Cancer Chemotherapy Reports. Part 1 1972, 56:343-356.
42. Yagoda A., Mukherji B., Young C., Etcubanas E., Lamonte C., Smith J.R., et al. Bleomycin, an antitumor antibiotic. Clinical experience in 274 patients. Annals of Internal Medicine 1972, 77:861-870.
43. Dalgleish A.G., Woods R.L., Levi J.A. Bleomycin pulmonary toxicity: its relationship to renal dysfunction. Medical and Pediatric Oncology 1984, 12:313-317.
44. Kawai K., Hinotsu S., Tomobe M., Akaza H. Serum creatinine level during chemotherapy for testicular cancer as a possible predictor of bleomycin-induced pulmonary toxicity. Japanese Journal of Clinical Oncology 1998, 28:546-550.
45. Senan S., Paul J., Thomson N., Kaye S.B. Cigarette smoking is a risk factor for bleomycin-induced pulmonary toxicity. European Journal of Cancer 1992, 28A:2084.
46. Hansen S.W., Groth S., Sorensen P.G., Rossing N., Rorth M. Enhanced pulmonary toxicity in smokers with germ-cell cancer treated with cis-platinum, vinblastine and bleomycin: a long-term follow-up. European Journal of Cancer and Clinical Oncology 1989, 25:733-736.
47. Sogal R.N., Gottlieb A.A., Boutros A.R., Ganapathi R.R., Tubbs R.R., Satariano P., et al. Effect of oxygen on bleomycin-induced lung damage. Cleveland Clinic Journal of Medicine 1987, 54:503-509.
48. Tryka A.F., Skornik W.A., Godleski J.J., Brain J.D. Potentiation of bleomycin-induced lung injury by exposure to 70% oxygen. Morphologic assessment. American Review of Respiratory Disease 1982, 126:1074-1079.
49. Donat S.M., Levy D.A. Bleomycin associated pulmonary toxicity: is perioperative oxygen restriction necessary. Journal of Urology 1998, 160:1347-1352.
50. Younes A., Connors J.M., Park S.I., Hunder N.N.H., Ansell S.M. Frontline therapy with brentuximab vedotin combined with ABVD or AVD in patients with newly diagnosed advanced stage Hodgkin Lymphoma. ASH Annual Meeting Abstracts 2011, 118:955.
51. Matthews J.H. Pulmonary toxicity of ABVD chemotherapy and G-CSF in Hodgkin's disease: possible synergy. Lancet 1993, 342:988.
52. Saxman S.B., Nichols C.R., Einhorn L.H. Pulmonary toxicity in patients with advanced-stage germ cell tumors receiving bleomycin with and without granulocyte colony stimulating factor. Chest 1997, 111:657-660.
53. Fossa S.D., Kaye S.B., Mead G.M., Cullen M., de Wit R., Bodrogi I., et al. Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. Journal of Clinical Oncology 1998, 16:716-724.
54. Macann A., Bredenfeld H., Muller R.P., Diehl V., Engert A., Eich H.T. Radiotherapy does not influence the severe pulmonary toxicity observed with the administration of gemcitabine and bleomycin in patients with advanced-stage Hodgkin's lymphoma treated with the BAGCOPP regimen: a report by the German Hodgkin's Lymphoma Study Group. International Journal of Radiation Oncology, Biology, Physics 2008, 70:161-165.
55. Horning S.J., Adhikari A., Rizk N., Hoppe R.T., Olshen R.A. Effect of treatment for Hodgkin's disease on pulmonary function: results of a prospective study. Journal of Clinical Oncology 1994, 12:297-305.
56. Azambuja E., Fleck J.F., Batista R.G., Menna Barreto S.S. Bleomycin lung toxicity: who are the patients with increased risk. Pulmonary Pharmacology and Therapeutics 2005, 18:363-366.
57. White D.A., Stover D.E. Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids. Chest 1984, 86:723-728.
58. Keijzer A., Kuenen B. Fatal pulmonary toxicity in testis cancer with bleomycin-containing chemotherapy. Journal of Clinical Oncology 2007, 25:3543-3544.
59. Sikdar T., MacVicar D., Husband J.E. Pneumomediastinum complicating bleomycin related lung damage. British Journal of Radiology 1998, 71:1202-1204.
60. 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. American Review of Respiratory Disease 1983, 128:880-883.
61. Wolkowicz J., Sturgeon J., Rawji M., Chan C.K. Bleomycin-induced pulmonary function abnormalities. Chest 1992, 101:97-101.
62. Rossi S.E., Erasmus J.J., McAdams H.P., Sporn T.A., Goodman P.C. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 2000, 20:1245-1259.
63. Costabel U., Guzman J. Bronchoalveolar lavage in interstitial lung disease. Current Opinion in Pulmonary Medicine 2001, 7:255-261.
64. Rhee C.K., Lee S.H., Yoon H.K., Kim S.C., Lee S.Y., Kwon S.S., et al. Effect of nilotinib on bleomycin-induced acute lung injury and pulmonary fibrosis in mice. Respiration 2011, 82:273-287.
65. Aono Y., Nishioka Y., Inayama M., Ugai M., Kishi J., Uehara H., et al. Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice. American Journal of Respiratory and Critical Care Medicine 2005, 171:1279-1285.
66. Daniels C.E., Wilkes M.C., Edens M., Kottom T.J., Murphy S.J., Limper A.H., et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. Journal of Clinical Investigation 2004, 114:1308-1316.
67. Carnevale-Schianca F., Gallo S., Rota-Scalabrini D., Sangiolo D., Fizzotti M., Caravelli D., et al. Complete resolution of life-threatening bleomycin-induced pneumonitis after treatment with imatinib mesylate in a patient with Hodgkin's lymphoma: hope for severe chemotherapy-induced toxicity. Journal of Clinical Oncology 2011, 29:e691-e693.
68. Viviani S., Zinzani P.L., Rambaldi A., Brusamolino E., Levis A., Bonfante V., et al. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. New England Journal of Medicine 2011, 365:203-212.
69. Connors J.M. Hodgkin's lymphoma - the great teacher. New England Journal of Medicine 2011, 365:264-265.
70. Sorensen P.G., Rossing N., Rorth M. Carbon monoxide diffusing capacity: a reliable indicator of bleomycin-induced pulmonary toxicity. European Journal of Respiratory Diseases 1985, 66:333-340.
71. Crooke S.T., Comis R.L., Einhorn L.H., Strong J.E., Broughton A., Prestayko A.W. Effects of variations in renal function on the clinical pharmacology of bleomycin administered as an iv bolus. Cancer Treatment Reports 1977, 61:1631-1636.
72. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics, 2010. CA: A Cancer Journal for Clinicians 2010, 60:277-300.
73. Foster R., Bihrle R. Current status of retroperitoneal lymph node dissection and testicular cancer: when to operate. Cancer Control: Journal of the Moffitt Cancer Center 2002, 9:277-283.
74. Sanchez-Munoz A., Jimenez-Rodriguez B., Navarro-Perez V., Medina-Rodriguez L., Llacer C., Vicioso L., et al. Targeted therapies in the treatment of germ cell tumors: the need for new approaches against orphan tumors. Critical Reviews in Oncology/Hematology 2012, 83:444-451.
75. Bosl G.J. Germ cell tumors: there is still plenty to learn. Journal of Clinical Oncology 1998, 16:1244-1247.
76. Bosl G.J., Geller N.L., Bajorin D., Leitner S.P., Yagoda A., Golbey R.B., et al. A randomized trial of etoposide+cisplatin versus vinblastine+bleomycin+cisplatin+cyclophosphamide+dactinomycin in patients with good-prognosis germ cell tumors. Journal of Clinical Oncology 1988, 6:1231-1238.
77. Culine S., Kerbrat P., Kramar A., Theodore C., Chevreau C., Geoffrois L., et al. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). Annals of Oncology 2007, 18:917-924.
78. Loehrer P.J., Johnson D., Elson P., Einhorn L.H., Trump D. Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. Journal of Clinical Oncology 1995, 13:470-476.
79. de Wit R., Roberts J.T., Wilkinson P.M., de Mulder P.H., Mead G.M., Fossa S.D., et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. Journal of Clinical Oncology 2001, 19:1629-1640.
80. Levi J.A., Raghavan D., Harvey V., Thompson D., Sandeman T., Gill G., Australasian Germ Cell Trial Group, et al. The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Journal of Clinical Oncology 1993, 11:1300-1305.
81. Kondagunta G.V., Bacik J., Bajorin D., Dobrzynski D., Sheinfeld J., Motzer R.J., et al. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. Journal of Clinical Oncology 2005, 23:9290-9294.
82. Einhorn L.H., Foster R.S. Bleomycin, etoposide, and cisplatin for three cycles compared with etoposide and cisplatin for four cycles in good-risk germ cell tumors: is there a preferred regimen?. Journal of Clinical Oncology 2006, 24:2597-2598. [author reply 8-9].
83. de Wit R., Stoter G., Kaye S.B., Sleijfer D.T., Jones W.G., ten Bokkel Huinink W.W., et al. Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. Journal of Clinical Oncology 1997, 15:1837-1843.
84. Grimison P.S., Stockler M.R., Thomson D.B., Olver I.N., Harvey V.J., Gebski V.J., et al. Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. Journal of the National Cancer Institute 2010, 102:1253-1262.
85. Massard C., Plantade A., Gross-Goupil M., Loriot Y., Besse B., Raynard B., et al. Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases. Annals of Oncology 2010, 21:1585-1588.
86. Fizazi K., Prow D.M., Do K.A., Wang X., Finn L., Kim J., et al. Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours. British Journal of Cancer 2002, 86:1555-1560.
87. Goodwin K.D., Lewis M.A., Long E.C., Georgiadis M.M. Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:5052-5056.
88. Sugiyama M., Kumagai T., Hayashida M., Maruyama M., Matoba Y. The 1.6-A crystal structure of the copper(II)-bound bleomycin complexed with the bleomycin-binding protein from bleomycin-producing Streptomyces verticillus. Journal of Biological Chemistry 2002, 277:2311-2320.