mitomycin (mitomycin-C; MTC)
Mutamycin

Available forms
Available by prescription only
Injection: 5-mg, 20-mg, 40-mg vials

Indications and dosages
  Dosage and indications may vary. Check current literature for recommended protocol. Not indicated as a single-agent primary therapy.
 Stomach and pancreatic adenocarcinoma (with other chemotherapy drugs); cancer of breast ◇, colon ◇, rectum ◇, head ◇, neck ◇, lung ◇, cervix ◇. Adults: 20 mg/m² I.V. as a single dose. Repeat cycle q 6 to 8 weeks, adjusting dose, if needed, as below.

Nadir after prior dose WBCs/ mm3 Platelets/ mm3 Percentage of prior dose to be given 2,000-2,999 25,000-74,999 70% < 2,000 < 25,000 50%

 Bladder cancer ◇. Adults: 20 to 60 mg intravesically once per week for 8 weeks.

Pharmacodynamics
Antineoplastic action: Mitomycin exerts its cytotoxic activity by a mechanism similar to that of the alkylating agents. The drug is converted to an active compound which forms cross-links between strands of DNA, inhibiting DNA synthesis. Mitomycin also inhibits RNA and protein synthesis to a lesser extent.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Distributes widely into body tissues; animal studies show that the highest levels are found in the kidneys followed by the muscle, eyes, lungs, intestines, and stomach. Drug doesn’t cross the blood-brain barrier.
Metabolism: Metabolized by hepatic microsomal enzymes; deactivated in the kidneys, spleen, brain, and heart.
Excretion: Excreted in urine, 10% as unchanged drug. A small portion is eliminated in bile and feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and those with thrombocytopenia, coagulation disorders, or an increase in bleeding tendency from other causes. Contraindicated as primary therapy as a single agent to replace surgery or radiotherapy. Don’t use in patients with serum creatinine greater than 1.7 mg/dl. Use cautiously in patients with recent or existing chickenpox or herpes zoster and in patients who have received previous cytotoxic therapy.

Interactions
Drug-drug. Vinca alkaloids: Acute shortness of breath and severe bronchospasm have occurred following use of vinca alkaloids in patients who had previously or simultaneously received mitomycin. Monitor patient carefully.

Adverse reactions
CNS: headache, neurologic abnormalities, confusion, drowsiness, fatigue, fever, pain, syncope.
EENT: blurred vision.
GI: nausea, vomiting, anorexia, diarrhea, hematemesis.
Hematologic: thrombocytopenia; leukopenia (may be delayed up to 8 weeks and may be cumulative with successive doses); hemolytic uremic syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure; hypertension.
Respiratory: interstitial pneumonitis, pulmonary edema, dyspnea, nonproductive cough, adult respiratory distress syndrome.
Skin: reversible alopecia; desquamation, induration, pruritus, and pain at injection site.
Other: septicemia; cellulitis, ulceration, and sloughing with extravasation.

Effects on lab test results
• May increase serum creatinine level.
• May decrease hemoglobin and WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, nausea, vomiting, and alopecia.
 Treatment is usually supportive and includes transfusion of blood components, antiemetics, and antibiotics for infections that may develop.

Special considerations
 ALERT Stop drug if WBC count is less than 4,000/mm³ or platelet count is less than 150,000/mm³. Give no repeat dose until blood counts go above these levels. If disease progresses after two courses of therapy, discontinue use.
 ALERT Don’t confuse this drug with mitoxantrone. Question any unfamiliar color of the drug.
• To reconstitute 5-mg vial, use 10 ml of sterile water for injection; to reconstitute 20-mg vial, use 40 ml of sterile water for injection; to reconstitute a 40-mg vial, use 80 ml sterile water for injection, to yield 0.5 mg/ml. Let stand at room temperature until complete dissolution occurs.
• Drug may be administered by I.V. push injection slowly over 5 to 10 minutes into the tubing of a freely flowing I.V. infusion.
• Drug can be further diluted to 100 to 150 ml with normal saline solution or D₅W for I.V. infusion (over 30 to 60 minutes or longer).
• Reconstituted solution remains stable for 1 week at room temperature and for 2 weeks if refrigerated.
• Mitomycin has been used intra-arterially to treat certain tumors, for example, into hepatic artery for colon cancer. It has also been given as a continuous daily infusion.
• Ulcers caused by extravasation develop late and dorsal to the extravasation site. Apply cold compresses for at least 12 hours.
• Observe patient for evidence of renal toxicity. Don’t give drug to patient with a serum creatinine level over 1.7 mg/dl.
• Continue CBC and blood studies at least 7 weeks after therapy is stopped. Monitor patient for signs of bleeding.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. To avoid risk of serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.

Patient education
• Tell patient to avoid exposure to people with infections.
• Warn patient not to receive immunizations during therapy and for several weeks afterward. Members of the same household shouldn’t receive immunizations during the same period.
• Reassure patient that hair should grow back after treatment has been discontinued.
• Tell patient to call promptly if he develops a sore throat or fever or notices unusual bruising or bleeding.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use