Mitomycin (Monograph)

Brand name: Mutamycin
Drug class: Antineoplastic Agents
VA class: AN200
Molecular formula: C₁₅H₁₈N₄O₅
CAS number: 50-07-7

Medically reviewed by Drugs.com on Jul 1, 2024. Written by ASHP.

Introduction

Antineoplastic agent; an antibiotic produced by Streptomyces caespitosus.^{100 c d}

Uses for Mitomycin

Adenocarcinoma of Stomach and Pancreas

Component of combination chemotherapeutic regimens for treatment of disseminated adenocarcinoma of the stomach or pancreas and as palliative treatment of these tumors when other treatment modalities are ineffective.^{100 121 d}

Response rates generally low (10–17%) and of short duration.^c

Not recommended for use as single-agent, primary therapy or as a replacement for appropriate surgery and/or radiation therapy.^{100 d}

Anal Cancer

A preferred regimen, in combination with fluorouracil, for primary treatment of anal cancer^{† [off-label]}.¹²¹

Bladder Cancer

Has been used for intravesical^{† [off-label]} treatment of residual tumor and/or as adjuvant therapy for prophylaxis of superficial bladder cancer^{† [off-label]}.^{113 115 120 121 130 131 138}

Causes regression of existing papillary tumor and reduces the rate of short-term tumor recurrence but has no effect on disease progression or overall survival.^{119 123 124 129 139}

Cervical Cancer

Has been used in cisplatin-containing combination chemotherapy regimens (e.g., bleomycin, cisplatin, mitomycin, and vincristine) for treatment of metastatic or recurrent cervical cancer^{† [off-label]}.^{132 135}

Other agents generally preferred for treatment of advanced cervical cancer^{† [off-label]}.^{136 137}

Non-small Cell Lung Cancer

Has been used for treatment of non-small cell lung cancer^† in combination with cisplatin and vinblastine (MVP) ^{121 146 149} or ifosfamide with mesna (MIC).^{121 150}

Other chemotherapeutic regimens (e.g., cisplatin with paclitaxel, vinorelbine, or gemcitabine) currently preferred for treatment of advanced non-small cell lung cancer^†.^{121 146}

Malignant Mesothelioma

Has been used for treatment of malignant mesothelioma^†.¹²¹

Head and Neck Carcinoma

Has been used as an adjunct to radiation therapy for treatment of squamous cell carcinoma of head and neck^†.¹⁴⁷

Breast Cancer

Has shown activity for treatment of metastatic breast cancer^†.¹⁴⁸

Mitomycin Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.^{100 d}

• Administer mitomycin only after complete hematologic recovery from any previous chemotherapy occurs.¹⁰⁰

Administration

Administer IV.^{100 c d}

Has been administered intravesically^†; notan approved route of administration.^{100 115 120 121 130 131 138 d}

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer via a functioning IV catheter;^{100 c d} some clinicians recommend administering the drug through tubing of an IV infusion.^c Use care to avoid extravasation.^{100 d} (See Mucocutaneous Effects under Cautions.)

Reconstitution

Reconstitute vial containing 5, 20, or 40 mg of mitomycin with 10, 40, or 80 mL of sterile water for injection, respectively, to provide a solution containing approximately 0.5 mg/mL.^{100 c d}

Shake vial to dissolve.^{100 c d} If the powder does not dissolve immediately, allow the vial to stand at room temperature until complete dissolution occurs.^{100 c d}

Dosage

Consult published protocols for dosages of mitomycin and other chemotherapeutic agents and the method and sequence of administration.^c

Individualize dosage based on clinical and hematologic response and tolerance of the patient and whether or not other myelosuppressive therapy also is being used.^{100 c d}

Reevaluate patients after each course of therapy and adjust dosages as needed.^{100 d}

Adults

Adenocarcinoma of Stomach and Pancreas

IV

Initially, 20 mg/m² as a single IV dose every 6–8 weeks.^{100 d} Doses >20 mg/m² are not more effective and increase risk of toxicity.^{100 d}

Adjust subsequent dosages according to the hematologic response to the previous dose.^{100 d} (See Table 1.)Do not administer repeat dosage until leukocyte count has returned to 4000/mm³ and platelet count to 100,000/mm³.^{100 d}

If disease continues to progress after 2 courses of therapy, discontinue the drug since likelihood of response is minimal.^{100 d}

Bladder Cancer†

Treatment of Superficial Bladder Cancer†

Intravesical^†

Usual dosage: 20–60 mg once weekly,^{115 116 118 120 125 126 127 128} administered as soon as possible following transurethral resection (TUR).^{117 128} For patients treated within 6–24 hours following TUR, a 6-month course of therapy generally is sufficient; however, for patients in whom intravesical therapy is instituted ≥24 hours following surgery, a 12-month course usually is recommended.^{117 128} No additional benefit demonstrated for continued maintenance therapy.^{115 116 120 124 128 131}

Special Populations

Hepatic Impairment

No special dosage recommendations at this time.^{100 d}

Renal Impairment

Do not administer if S_cr >1.7 mg/dL.^{100 d} (See Renal Effects under Cautions.)

Geriatric Patients

No special dosage recommendations at this time.^{100 d}

Cautions for Mitomycin

Contraindications

• Thrombocytopenia, coagulation disorder, or an increase in bleeding tendency due to other causes.^{100 c d} (See Hematologic Effects under Cautions.)

• Known hypersensitivity or idiosyncratic reaction to mitomycin.^{100 c d}

Warnings/Precautions

Warnings

Toxicity

Highly toxic drug with a low therapeutic index.^c Administer only under the supervision of a qualified clinician experienced in use of cancer chemotherapeutic agents.^{100 c d} (See Boxed Warning and also see Hematologic Effects, Renal Effects, Hemolytic Uremic Syndrome, and Respiratory Effects under Cautions.)

Hematologic Effects

High incidence of cumulative myelosuppression, principally thrombocytopenia and leukopenia.^{100 c d} (See Boxed Warning.) Not related to total dose; however, occurs more frequently with certain dosage regimens.^c

Monitor hematologic status (platelet count, leukocyte count, differential, PT, bleeding time, and hemoglobin) repeatedly during therapy and for ≥8 weeks afterwards.^{100 c d} Withhold therapy if leukocyte count <4000/mm³, platelet count <100,000/mm³, or if a progressive decline in either occurs.^{100 d} (See Table 1.)

Myelosuppression may occur anytime within 8 weeks after initiation of therapy; may be severe (e.g., platelet count ≤50,000/mm³, leukocyte count ≤2000/mm³).^{100 c d} Nadir during 4–6 weeks of therapy.^c Recovery usually occurs ≤10 weeks after therapy discontinued; however, about 25% of cases may be irreversible.^{100 d}

Hemorrhagic Complications

Bleeding due to thrombocytopenia may occur.^c Platelet transfusions may be needed.^c

Infectious Complications

Life-threatening infections secondary to leukopenia (e.g., septicemia) reported.^{100 c d}

Renal Effects

Renal toxicity (e.g., increased BUN and/or S_cr) reported.^{100 c d} Possibly related to total dose administered (e.g., low risk at cumulative doses <50 mg/m²; substantially increases with higher cumulative doses);^{101 108} however, not clearly established.^{100 d}

Monitor renal function.¹⁰⁰ Do not administer if S_cr >1.7 mg/dL.^{100 d}

Renal failure also may occur as a component of hemolytic uremic syndrome.^{100 101 102 103 104 105 106 107 108} (See Hemolytic Uremic Syndrome under Cautions and also see Boxed Warning.)

Fetal/Neonatal Morbidity

May cause fetal harm; teratogenicity demonstrated in animals.^{100 d}

Safe use of mitomycin in pregnant women not established.^{100 d}

Major Toxicities

Hemolytic Uremic Syndrome

Hemolytic uremic syndrome, a severe and often fatal syndrome of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (platelet count ≤100,000/mm³), and irreversible renal failure (S_cr ≥1.6 mg/dL), reported.^{100 101 102 103 104 105 106 107 108 d} Pulmonary edema also may be a component; may be a particularly grave prognostic factor.^{100 104 d} Other complications include neurologic abnormalities and hypertension.^{100 d} (See Boxed Warning.)

Syndrome can vary from a chronic course with mild anemia and slowly progressive renal impairment to a fulminant course with severe anemia, rapid deterioration of renal function, and death.^{101 102 103 104 105 106 107 108}

May occur at any time during therapy (with or without other antineoplastic agents); however, most cases occur at doses ≥60 mg.^{100 d} Blood transfusion may exacerbate symptoms.^{100 d}

Closely monitor patients receiving mitomycin doses ≥60 mg for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function.^{100 d}

Optimum management of syndrome not established; use of systemic corticosteroids, plasma exchange, plasmapheresis, and/or IV vincristine beneficial in some patients, and early treatment may be preferred.^{103 104 105 106 107 108} (See Specific Drugs under Interactions.) Manufacturer states that therapy for syndrome is investigational.^{100 d}

General Precautions

Mucocutaneous Effects

Extremely irritating to tissues.^c Mucocutaneous toxicity (e.g., mouth ulcers, alopecia, desquamation, pruritus) may occur; appears related to the total dose given.^{c d}

Extravasation possible; may cause severe cellulitis, ulceration, and tissue sloughing.^{100 d} May occur with or without symptoms (e.g., stinging or burning during administration) and even when blood returns well during initial aspiration of infusion needle.^{100 d} (See IV Administration under Dosage and Administration.)

Possible pain on injection, induration, thrombophlebitis, and paresthesia.^c Delayed erythema and/or ulceration at or distant from the injection site possible weeks to months after administration despite the lack of apparent evidence of extravasation.^{100 d}

Respiratory Effects

Possibly severe or life-threatening acute bronchospasm and/or dyspnea may occur a few minutes to several hours after administration of a vinca alkaloid (e.g., vinblastine) in patients who have been previously or simultaneously treated with mitomycin.^{100 c d} Bronchodilators, corticosteroids, and/or oxygen may produce symptomatic relief.^{100 d}

ARDS reported in some patients receiving mitomycin in combination with other antineoplastic agents and maintained at fraction of inspired oxygen (FIO₂) concentrations >50% perioperatively.^{100 d} Use only enough oxygen to provide adequate arterial saturation.^{100 d}

Monitor patients for evidence of pulmonary toxicity (e.g., dyspnea with a nonproductive cough, radiographic evidence of pulmonary infiltrates) and for changes in fluid balance; avoid overhydration.^{100 d} If pulmonary toxicity develops, discontinue therapy if other etiologies can be excluded.^{100 d}

Intravesical Instillation

Bladder fibrosis/contraction reported;^{100 d} may require cystectomy.^{100 d}

Asymptomatic ulcers at the site of resected carcinoma of the bladder^{109 110 111} and calcification of bladder wall reported.¹¹²

Possible local irritation (i.e., cystitis); local toxicity increases with the number and frequency of instillations and with the dose administered.¹¹⁵

GI Effects

Nausea and vomiting may occur within 1–2 hours of IV administration.^{100 c d} Vomiting usually subsides rapidly but nausea can continue for 2–3 days.^c

Specific Populations

Pregnancy

Category C.^{100 d} (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known whether mitomycin is distributed into milk.^{100 d} Discontinue nursing during mitomycin therapy.^{100 d}

Pediatric Use

Safety and efficacy not established.^{100 d}

Renal Impairment

Do not use if S_cr >1.7 mg/dL.^{100 d} Monitor renal function prior to and periodically during therapy.^{100 d} (See Renal Effects under Cautions.)

Common Adverse Effects

IV administration: Myelosuppression, nausea, vomiting, anorexia, stomatitis, fever, alopecia.^{100 d}

Intravesical^† instillation: Local irritation (i.e., cystitis).¹¹⁵

Drug Interactions

Specific Drugs

Mitomycin Pharmacokinetics

Distribution

Extent

Rapidly distributed into tissues.^c

In animals, highest concentrations found in the kidneys, followed by muscles, eyes, lungs, intestines, and stomach; not detectable in the liver, spleen, or brain (rapidly inactivate mitomycin).^c

Higher concentrations of the drug are generally present in cancer tissues than in normal tissues.^c

Not known whether mitomycin is distributed into milk.^{100 d}

Elimination

Metabolism

Rapidly inactivated in microsomal fraction of the liver and also in the kidneys, spleen, brain, and heart, which contain high concentrations of enzymes capable of metabolizing the drug.^{100 c}

Elimination Route

Excreted principally in urine (about 10% as active drug) and to a small extent in bile.^{100 c d}

Rate of clearance inversely proportional to the maximum serum concentration because of saturation of degradative pathways.^{100 d}

Half-life

For 30-mg IV injection: 17 minutes.^{100 d}

Stability

Storage

Parenteral

Powder for Injection

15–30°C.^{c d} Protect from light^c and avoid excessive heat (>40°C).^{100 c d} Commercially available mitomycin powder is stable for at least 4 years at room temperature.^c

Reconstituted solutions are stable for 7 days at room temperature and for 14 days at 2–8°C.^{100 c d} Protect from light.^d

Compatibility

Parenteral

Solution Compatibility100 HID

Solutions of mitomycin diluted to a concentration of 20–40 mcg/mL are stable at room temperature for 3 hours in 5% dextrose injection, 12 hours in 0.9% sodium chloride, and 24 hours in sodium lactate injection.^{100 c d}

Drug Compatibility

The combination of mitomycin 5–15 mg and heparin sodium 1000–10,000 units in 30 mL of 0.9% sodium chloride injection is stable for 48 hours at room temperature.^{100 d}

Actions and Spectrum

• Mechanism of antineoplastic activity similar to that of other alkylating agents.^c

• Enzymatic reduction of mitomycin within susceptible cells may be necessary for antineoplastic activity.^c

• Activated mitomycin appears to selectively inhibit the synthesis of deoxyribonucleic acid (DNA) by causing cross-linking of DNA.^{100 c d} In high concentrations, may also inhibit RNA and protein synthesis.^{100 d}

• Active against gram-positive bacteria and some viruses; however cytotoxicity precludes use as an anti-infective agent.^c

Advice to Patients

• Importance of advising patients of potentially life-threatening hematologic (e.g., myelosuppression), respiratory, and renal toxicities associated with mitomycin therapy.^{100 c d}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{100 d}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., bleeding disorders).^{100 d}

• Importance of informing patients of other important precautionary information.^{100 d} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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