No

Antineoplastic Agent, Antibiotic

Therapy of disseminated adenocarcinoma of stomach or pancreas in combination with other approved chemotherapeutic agents; bladder cancer, colorectal cancer

D

Platelet counts <75,000/mm³; leukocyte counts <3,000/mm³ or serum creatinine >1.7 mg/dL; thrombocytopenia, hypersensitivity to mitomycin or any component

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Use with caution in patients with impaired renal or hepatic function, myelosuppression. Follow hemoglobin, hematocrit, BUN, and creatinine closely after therapy especially after second and subsequent cycles. Bone marrow suppression, notably thrombocytopenia and leukopenia, may contribute to the development of a secondary infection; hemolytic uremic syndrome, a serious and often fatal syndrome, has occurred in patients receiving long-term therapy and is correlated with total dose and total duration of therapy; mitomycin is potentially carcinogenic and teratogenic.

>10%:

Gastrointestinal: Nausea and vomiting (mild to moderate) seen in almost 100% of patients; usually begins 1-2 hours after treatment and persists for 3 hours to 4 days; other toxicities include stomatitis, hepatotoxicity, diarrhea, anorexia

Emetic potential: Moderate (30% to 60%)

Time course of nausea/vomiting: Onset: 1-2 hours; Duration: 48-72 hours

Local: Extravasation: May cause severe tissue irritation if infiltrated; can progress to cellulitis, ulceration, and sloughing of tissue. Refer to institutional policy for treatment.

Vesicant chemotherapy

Hematologic: Myelosuppressive: Dose-related toxicity and may be cumulative; related to both total dose (incidence higher at doses >50 mg) and schedule, may occur at anytime within 8 weeks of treatment.

WBC: Moderate

Platelets: Severe

Onset (days): 21

Nadir (days): 36

Recovery (days): 42-56

1% to 10%:

Dermatologic: Discolored fingernails (violet), alopecia

Neuromuscular & skeletal: Extremity paresthesia

Renal: Elevation of creatinine seen in 2% of patients; hemolytic uremic syndrome observed in <10% of patients and is dose-dependent (doses greater than or equal to 60 mg or >50 mg/m² have higher risk)

Respiratory: Interstitial pneumonitis or pulmonary fibrosis have been noticed in 7% of patients, and it occurs independent of dosing. Manifested as dry cough and progressive dyspnea; usually is responsive to steroid therapy.

<1%: Cardiac failure (in patients treated with doses >30 mg/m²), malaise, fever, pruritus, rash, mouth ulcers, bone marrow suppression (leukopenia, thrombocytopenia), microangiopathic hemolytic anemia, thrombophlebitis, paresthesia, weakness

Symptoms of overdose include bone marrow suppression, nausea, vomiting, alopecia

Increased toxicity:

Vinca alkaloids acute shortness of breath or bronchospasm

Doxorubicin may enhance cardiac toxicity

Store intact vials of lyophilized powder at room temperature

Dilute powder with SWI to a concentration of 0.5 mg/mL as follows: Solution is stable for 7 days at room temperature and 14 days at refrigeration if protected from light

5 mg = 10 mL

20 mg = 40 mL

Further dilution in NS is stable for 24 hours at room temperature

Standard I.V. dilution:

I.V. push: Dose/syringe (concentration = 0.5 mg/mL)

Maximum syringe size for IVP is a 30 mL syringe and syringe should be less than or equal to 75% full

Syringe is stable for 7 days at room temperature and 14 days at refrigeration if protected from light

IVPB: Dose/100 mL NS

IVPB solution is stable for 24 hours at room temperature

Isolated from Streptomyces caespitosus; acts primarily as an alkylating agent and produces DNA cross-linking (primarily with guanine and cytosine pairs); cell-cycle nonspecific; inhibits DNA and RNA synthesis by alkylation and cross-linking the strands of DNA

Absorption: Fairly well from the GI tract

Distribution: V_d: 22 L/m²; high drug concentrations found in kidney, tongue, muscle, heart, and lung tissue; probably not distributed into the CNS

Metabolism: Hepatic

Half-life: 23-78 minutes; Terminal: 50 minutes

Elimination: Primarily in metabolism, followed by urinary excretion (<10% as unchanged drug) and to a small extent biliary excretion

Refer to individual protocols

Single-agent therapy: 20 mg/m² every 6-8 weeks

Note: Doses >20 mg/m² have not been shown to be more effective, and are more toxic.

Combination therapy: 10 mg/m² every 6-8 weeks

Bone marrow transplant:

40-50 mg/m²

2-40 mg/m²/day for 3 days

Total cumulative dose should not exceed 50 mg/m²; see below: ( nadir after prior dose per mm³)

Leukocytes 4000; platelets >100,000: 100% of prior dose to be given

Leukocytes 3000-3999; platelets 75,000-99,999: 100% of prior dose to be given

Leukocytes 2000-2999; platelets 25,000-74,999: 70% of prior dose to be given

Leukocytes 2000; platelets <25,000: 50% of prior dose to be given

Dosing adjustment in renal impairment:

Cl_cr <10 mL/minute: Administer 75% of normal dose

or

Serum creatinine 1.6-2.4 mg/dL: Administer 50% of the dose

Serum creatinine >2.4 mg/dL: Do not administer

Hemodialysis: Unknown

CAPD effects: Unknown

CAVH effects: Unknown

Dosing adjustment in hepatic impairment:

Bilirubin 1.5-3 mg/dL: Administer 50% of the dose

Bilirubin >3.1 mg/dL: Administer 25% of the dose

or

Bilirubin >3.0 mg/dL OR hepatitic enzymes >3 times normal: Administer 50% of the dose

Intravesicular instillations for bladder carcinoma: 20-40 mg/dose (1 mg/mL in sterile aqueous solution) instilled into the bladder for 3 hours repeated up to 3 times/week for up to 20 procedures per course

Platelet count, CBC with differential, hemoglobin, prothrombin time, renal and pulmonary function tests

May cause drowsiness

Myelosuppression is common; avoid with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be given I.V. Make note of scheduled return dates. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. You may experience, rash, skin lesions, loss of hair, or permanent sterility. Small frequent meals may help if you experience nausea, vomiting, loss of appetite. Frequent mouth care will help reduce the incidence of mouth sores. Use caution when driving or engaging in tasks that require alertness because you may experience dizziness, drowsiness, syncope, or blurred vision. Report difficulty breathing, swelling of extremities, or sudden weight gain; burning, pain, or redness at infusion site; unusual bruising or bleeding; pain on urination; or other adverse effects. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Do not breast-feed.

Extravasation management:

Care should be taken to avoid extravasation. If extravasation occurs, the site should be observed closely; these injuries frequently cause necrosis; a plastic surgery consult may be required.

Few agents have been effective as antidotes, but there are reports in the literature of some benefit with dimethylsulfoxide (DMSO). Delayed dermal reactions with mitomycin are possible, even in patients who are asymptomatic at time of drug administration.

Powder for injection: 5 mg, 20 mg, 40 mg

Alberts DS and Dorr RT, "Case Report: Topical DMSO for Mitomycin C-Induced Skin Ulceration," Oncol Nurs Forum, 1991, 18(4):693-5.

den Hartigh J, Verweij J, and Pinedo HM, "Mitomycin C," Cancer Chemother Biol Response Modif, 1987, 9:56-62.

Doll DC, Weiss RB and Issell BF, "Mitomycin: Ten Years After Approval for Marketing," J Clin Oncol, 1985, 3(2):276-86.

Gandolfi SA, Vecchi M and Braccio L, "Decrease of Intraocular Pressure After Subconjunctival Injection of Mitomycin in Human Glaucoma," Arch Ophthalmol, 1995, 113(5):582-5.

Hortobagyi GN, "Mitomycin: Its Evolving Role in the Treatment of Breast Cancer," Oncology, 1993, 50(Suppl 1):1-8.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Verweij J, "Mitomycins," Cancer Chemother Biol Response Modif, 1996, 16:48-56.