Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Mitomycin-C pulmonary toxicity

Edward D Chan, MD
Talmadge E King, Jr, MD
Section Editor
Kevin R Flaherty, MD, MS
Deputy Editors
Helen Hollingsworth, MD
Diane MF Savarese, MD


Mitomycin-C (MMC), an antineoplastic antibiotic derived from Streptomyces caespitosus, is a cell cycle-specific alkylating agent [1]. Although it is active against a wide variety of tumors, newer agents have largely replaced MMC except in anal cancer; outside of the United States, MMC is infrequently used for treatment of advanced non-small cell lung cancer (NSCLC), and breast cancer. As with many other chemotherapeutic agents, most of the adverse effects of MMC are dose-related, including myelosuppression (which is typically delayed in onset), nausea, vomiting, diarrhea, stomatitis, dementia, and alopecia [1-3]. Pulmonary toxicity associated with MMC is unpredictable, but more likely to occur at higher doses.

The pulmonary complications associated with MMC therapy will be reviewed here. A general discussion of the clinical presentation, pathogenesis, diagnosis, differential diagnosis, and management of antineoplastic agent-induced pulmonary toxicity is presented separately. (See "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment".)


Pulmonary toxicity associated with MMC is unpredictable, but more likely to occur at higher doses (in most literature reviews, >20 mg/m2) [4-7]. The frequency of clinically significant adverse pulmonary reactions from MMC is estimated to be between 2 and 12 percent [4,7-9].

The various pulmonary disorders that have been described with MMC include:

Acute bronchospasm

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Sep 16, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Verweij J, Pinedo HM. Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs 1990; 1:5.
  2. Orwoll ES, Kiessling PJ, Patterson JR. Interstitial pneumonia from mitomycin. Ann Intern Med 1978; 89:352.
  3. Folman RS. Experience with mitomycin in the treatment of non-small cell lung cancer. Oncology 1993; 50 Suppl 1:24.
  4. Verweij J, van Zanten T, Souren T, et al. Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis. Cancer 1987; 60:756.
  5. Ospovat I, Siegelmann-Danieli N, Grenader T, et al. Mitomycin C and vinblastine: an active regimen in previously treated breast cancer patients. Tumori 2009; 95:683.
  6. Rao SX, Ramaswamy G, Levin M, McCravey JW. Fatal acute respiratory failure after vinblastine-mitomycin therapy in lung carcinoma. Arch Intern Med 1985; 145:1905.
  7. Okuno SH, Frytak S. Mitomycin lung toxicity. Acute and chronic phases. Am J Clin Oncol 1997; 20:282.
  8. Castro M, Veeder MH, Mailliard JA, et al. A prospective study of pulmonary function in patients receiving mitomycin. Chest 1996; 109:939.
  9. Linette DC, McGee KH, McFarland JA. Mitomycin-induced pulmonary toxicity: case report and review of the literature. Ann Pharmacother 1992; 26:481.
  10. Wada H, Nakano Y, Yamada H, et al. Intravesical mitomycin-C-induced interstitial pneumonia. Respiration 2010; 80:256.
  11. González-Moreno S, Lambert LA, Mansfield PF. Interstitial pneumonitis: an exceptional toxicity of hyperthermic intraperitoneal mitomycin C. Eur J Surg Oncol 2008; 34:482.
  12. Chen MY, Chiles C, Loggie BW, et al. Thoracic complications in patients undergoing intraperitoneal heated chemotherapy with mitomycin following cytoreductive surgery. J Surg Oncol 1997; 66:19.
  13. Luedke D, McLaughlin TT, Daughaday C, et al. Mitomycin C and vindesine associated pulmonary toxicity with variable clinical expression. Cancer 1985; 55:542.
  14. Kris MG, Pablo D, Gralla RJ, et al. Dyspnea following vinblastine or vindesine administration in patients receiving mitomycin plus vinca alkaloid combination therapy. Cancer Treat Rep 1984; 68:1029.
  15. Rouzaud P, Estivals M, Pujazon MC, et al. [Respiratory complications of the vinorelbine-mitomycin combination]. Rev Mal Respir 1999; 16:81.
  16. Thomas P, Pradal M, Le Caer H, et al. [Acute bronchospasm due to periwinkle alkaloid and mitomycin association]. Rev Mal Respir 1993; 10:268.
  17. Hohneker JA. A summary of vinorelbine (Navelbine) safety data from North American clinical trials. Semin Oncol 1994; 21:42.
  18. Buzdar AU, Legha SS, Luna MA, et al. Pulmonary toxicity of mitomycin. Cancer 1980; 45:236.
  19. Konits PH, Aisner J, Sutherland JC, Wiernik PH. Possible pulmonary toxicity secondary to vinblastine. Cancer 1982; 50:2771.
  20. Rivera MP, Kris MG, Gralla RJ, White DA. Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy. Am J Clin Oncol 1995; 18:245.
  21. Andrews AT, Bowman HS, Patel SB, Anderson WM. Mitomycin and interstitial pneumonitis. Ann Intern Med 1979; 90:127.
  22. Urban T, Bedin A, Baud M, et al. Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer. Lung Cancer 1996; 14:109.
  23. Klein DS, Wilds PR. Pulmonary toxicity of antineoplastic agents: anaesthetic and postoperative implications. Can Anaesth Soc J 1983; 30:399.
  24. Thompson CC, Bailey MK, Conroy JM, Bromley HR. Postoperative pulmonary toxicity associated with mitomycin-C therapy. South Med J 1992; 85:1257.
  25. Müller NL, White DA, Jiang H, Gemma A. Diagnosis and management of drug-associated interstitial lung disease. Br J Cancer 2004; 91 Suppl 2:S24.
  26. Ballen KK, Weiss ST. Fatal acute respiratory failure following vinblastine and mitomycin administration for breast cancer. Am J Med Sci 1988; 295:558.
  27. Chang AY, Kuebler JP, Pandya KJ, et al. Pulmonary toxicity induced by mitomycin C is highly responsive to glucocorticoids. Cancer 1986; 57:2285.
  28. Chambers SK, Flynn SD, Del Prete SA, et al. Bleomycin, vincristine, mitomycin C, and cis-platinum in gynecologic squamous cell carcinomas: a high incidence of pulmonary toxicity. Gynecol Oncol 1989; 32:303.
  29. Vrdoljak E, Boban M, Omrcen T, et al. Combination of capecitabine and mitomycin C as first-line treatment in patients with metastatic breast cancer. Neoplasma 2011; 58:172.
  30. Fielding JW, Stockley RA, Brookes VS. Interstitial lung disease in a patient treated with 5-fluorouracil and mitomycin C. Br Med J 1978; 2:602.
  31. Limper AH. Chemotherapy-induced lung disease. Clin Chest Med 2004; 25:53.
  32. Wibmer T, Kropf C, Merk T, et al. Efficacy and safety of combination chemotherapy with mitomycin and vinorelbine for the treatment of advanced non-small cell lung cancer. Lung Cancer 2008; 60:231.
  33. Niell HB, Griffin JP, West WH, Neely CL. Combination chemotherapy with mitomycin C, methotrexate, cisplatin, and vinblastine in the treatment of non-small cell lung cancer. Cancer 1984; 54:1260.
  34. Rancati T, Ceresoli GL, Gagliardi G, et al. Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study. Radiother Oncol 2003; 67:275.
  35. Makris D, Scherpereel A, Copin MC, et al. Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer. BMC Cancer 2007; 7:150.
  36. Sagawa M, Takahashi S, Usuda K, et al. [Interstitial pneumonia after CMC (CDDP, MMC, CPM) therapy]. Gan No Rinsho 1988; 34:150.
  37. Raderer M, Kornek G, Hejna M, et al. Acute pulmonary toxicity associated with high-dose vinorelbine and mitomycin C. Ann Oncol 1996; 7:973.
  38. Gunstream SR, Seidenfeld JJ, Sobonya RE, McMahon LJ. Mitomycin-associated lung disease. Cancer Treat Rep 1983; 67:301.
  39. Jolivet J, Giroux L, Laurin S, et al. Microangiopathic hemolytic anemia, renal failure, and noncardiogenic pulmonary edema: a chemotherapy-induced syndrome. Cancer Treat Rep 1983; 67:429.
  40. Torra R, Poch E, Torras A, et al. Pulmonary hemorrhage as a clinical manifestation of hemolytic-uremic syndrome associated with mitomycin C therapy. Chemotherapy 1993; 39:453.
  41. McCarthy JT, Staats BA. Pulmonary hypertension, hemolytic anemia, and renal failure. A mitomycin-associated syndrome. Chest 1986; 89:608.
  42. Gagnadoux F, Capron F, Lebeau B. Pulmonary veno-occlusive disease after neoadjuvant mitomycin chemotherapy and surgery for lung carcinoma. Lung Cancer 2002; 36:213.
  43. Schraufnagel DE, Sekosan M, McGee T, Thakkar MB. Human alveolar capillaries undergo angiogenesis in pulmonary veno-occlusive disease. Eur Respir J 1996; 9:346.
  44. Waldhorn RE, Tsou E, Smith FP, Kerwin DM. Pulmonary veno-occlusive disease associated with microangiopathic hemolytic anemia and chemotherapy of gastric adenocarcinoma. Med Pediatr Oncol 1984; 12:394.
  45. Perros F, Günther S, Ranchoux B, et al. Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models. Circulation 2015; 132:834.
  46. Belge C, Quarck R, Delcroix M. Letter by Belge et al Regarding Article, "Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models". Circulation 2016; 133:e591.
  47. Huggins JT, Sahn SA. Drug-induced pleural disease. Clin Chest Med 2004; 25:141.
  48. Veen EJ, Dikkers FG. Topical use of MMC in the upper aerodigestive tract: a review on the side effects. Eur Arch Otorhinolaryngol 2010; 267:327.
  49. Hueman EM, Simpson CB. Airway complications from topical mitomycin C. Otolaryngol Head Neck Surg 2005; 133:831.
  50. Agrawal N, Morrison GA. Laryngeal cancer after topical mitomycin C application. J Laryngol Otol 2006; 120:1075.
  51. Schrijvers D, Catimel G, Highley M, et al. KW-2149-induced pulmonary toxicity is not prevented by corticosteroids: a phase I and pharmacokinetic study. Anticancer Drugs 1999; 10:633.
  52. Spain RC. The case for mitomycin in non-small cell lung cancer. Oncology 1993; 50 Suppl 1:35.
  53. Danson S, Middleton MR, O'Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 2003; 98:542.
  54. Booton R, Lorigan P, Anderson H, et al. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol 2006; 17:1111.
  55. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996; 14:2527.