Mitomycin

(aka Mitomycin-C)

Epidemiology

  • Indications
    • Bladder Cancer
    • Lung Cancer
    • Anorectal Cancer
    • Metastatic Breast Cancer
    • Metastatic Hepatocellular Carcinoma
    • Esophageal Cancer
  • Onset of Pulmonary Toxicity
    • Pulmonary toxicity typically occurs during second-third cycle of mitomycin C therapy
  • Cumulative Dose Effect of Pulmonary Toxicity
    • Linear relationship between mitomycin C dose and incidence of pulmonary toxicity
    • Pulmonary fibrosis is unlikely at doses <30 mg/m2
  • Synergistic Factors Contributing to Pulmonary Toxicity
    • High Inspired Oxygen
    • Radiation Therapy
    • Concomitant Administration of Bleomycin, Doxorubicin, or Cyclophosphamide

Physiology

  • Mitomycin C is an antineoplastic antibiotic isolated from Streptomyces caespitosus
    • Cell cycle-specific alkylating agent

Adverse Effects

Pulmonary Adverse Effects (8-39% of cases)

  • Acute Dyspnea (see Dyspnea): may occur acutely after administration (during or several hours after vinblastine infusion)
  • Bronchospasm (see Obstructive Lung Disease):
  • Acute Pneumonitis (see Pneumonia)
  • Hemolytic-Uremic Syndrome (see Hemolytic-Uremic Syndrome)
    • Epidemiology
      • Has been reported particularly when mitomycin C is used in conjunction with 5-fluorouracil (5-FU)
      • Most cases occur 6-12 mo after start of mitomycin C treatment
      • May be precipitated by blood transfusions
    • Diagnosis
      • Renal Biopsy and Open Lung Biopsy: microangiopathic changes, intimal arteriolar hyperplasia, prominent nuclear atypia of capillary cells, capillary fibrin thrombi
    • Clinical
    • Treatment
      • Plasma Exchange (with or without dialysis)
      • Corticosteroids
    • Prognosis
      • Mortality with ARDS: as high as 95%
      • Mortality without ARDS: 50%
  • Interstitial Lung Disease (see Interstitial Lung Disease-Etiology)
    • Diagnosis
      • ABG: hypoxemia
      • CXR/Chest CT
        • Diffuse or localized interstitial infiltrates: lower-lobe predominance
      • PFT’s: DLCO may not fall prior to onset of ILD -> unreliable predictor of ILD
    • Treatment
      • Response to corticosteroids (more so than with other chemotherapeutic agents)
      • Prednisone 1 mg/kg/day: may require weeks-months before tapering
      • Failure to return to baseline may occur
  • Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage)
    • Diagnosis
      • PFT’s: increased DLCO during alveolar hemorrhage
      • ANCA: may be seen
      • OLB: capillaritis
  • Cryptogenic Organizing Pneumonia (see Cryptogenic Organizing Pneumonia and Lung Nodule or Mass)
    • May appear as nodular infiltrates
  • Pulmonary Alveolar Proteinosis (see Pulmonary Alveolar Proteinosis)
  • Pleural Effusion (see Pleural Effusion-Exudate)

Other Adverse Effects

  • Myelosuppression
    • Delayed onset of thrombocytopenia and leukopenia: nadirs between 4-6 weeks after a single dose
  • Glomerulonephritis (see Acute Glomerulonephritis)
    • Elevated ANCA may be seen

Treatment

  • Avoid Further Mitomycin
  • Avoid Vinca Alkaloids
  • Avoid High FiO2

References

  • Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs 1990; 1:5
  • Interstitial pneumonia from mitomycin. Ann Intern Med 1978; 89:352
  • A prospective study of pulmonary function in patients receiving mitomycin. Chest 1996; 109:939
  • Mitomycin lung toxicity. Acute and chronic phases. Am J Clin Oncol 1997; 20:282
  • Mitomycin-induced pulmonary toxicity: case report and review of the literature. Ann Pharmacother 1992; 26:481
  • Dyspnea following vinblastine or vindesine administration in patients receiving mitomycin plus vinca alkaloid combination therapy. Cancer Treat Rep 1984; 68:1029
  • Syndrome of acute dyspnea related to combined mitomycin plus vinca alkaloid chemotherapy. Am J Clin Oncol 1995; 18:245
  • Intravesical mitomycin-C-induced interstitial pneumonia. Respiration 2010; 80:256
  • Pulmonary angiomatoid vascular changes in mitomycin C-associated hemolytic-uremic syndrome. Arch Pathol Lab Med 1985; 109:877
  • Pulmonary hemorrhage as a clinical manifestation of hemolytic-uremic syndrome associated with mitomycin C therapy. Chemotherapy 1993; 39:453
  • Interstitial pneumonitis following intrapleural chemotherapy. World J Surg Oncol 2009; 7:17
    Thoracic complications in patients undergoing intraperitoneal heated chemotherapy with mitomycin following cytoreductive surgery. J Surg Oncol 1997; 66:19