(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
- Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS): occurs in 50% of cases
- Microangiopathic Hemolytic Anemia (see Hemolytic Anemia)
- Acute Kidney Injury (see Acute Kidney Injury)
- Pulmonary Hypertension (see Pulmonary Hypertension)
- Treatment
- Plasma Exchange (with or without dialysis)
- Corticosteroids
- Prognosis
- Mortality with ARDS: as high as 95%
- Mortality without ARDS: 50%
- Epidemiology
- 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
- Diagnosis
- Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage)
- Diagnosis
- PFT’s: increased DLCO during alveolar hemorrhage
- ANCA: may be seen
- OLB: capillaritis
- Diagnosis
- 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