DRUG NAME: Mitomycin - bccancer.bc.ca

1 Mitomycin DRUG NAME: Mitomycin SYNONYM(S): Mitomycin C,1 MMC1. COMMON TRADE NAME(S): MUTAMYCIN . CLASSIFICATION: antitumour antibiotic Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: 2. Mitomycin is derived from Streptomyces caespitosus and has antineoplastic activity similar to that of the alkylating 3 2,3. agents. Mitomycin selectively inhibits the synthesis of DNA by causing cross-linking, degrades preformed DNA, 4. and causes nuclear lysis and formation of giant cells. At high concentrations, cellular RNA and protein synthesis 2,3. may also be suppressed. Mitomycin is cell cycle phase-nonspecific, although it has its maximum effect in late G- 4. and early S-phases. PHARMACOKINETICS: Oral Absorption no information found 2,3. Distribution rapidly cleared from plasma 4. cross blood brain barrier? unlikely 4 2. volume of distribution 22 L/m plasma protein binding no information found 3.

2 Metabolism rapidly inactivated in the liver, kidneys, spleen, brain, heart, and plasma ; metabolic pathways saturated at relatively low doses active metabolite(s) no information found 3. inactive metabolite(s) yes 2,4. Excretion primarily hepatic ; occurs in other tissues 10% unchanged; dose related 2,3. urine 3. feces minimal 4. terminal half life 50 min clearance no information found Children excretion in children is similar to adults Adapted from standard reference2 unless specified otherwise. USES: Primary uses: Other uses: 3 3. Anal cancer Breast cancer 3. *Bladder cancer (intravesical) Cervical cancer 5. *Colon cancer Conjunctival melanoma (topical). 3. *Gastric cancer Lung cancer, non-small cell 3,6,7 5. Head and neck cancer Ocular surface squamous neoplasia (topical). 8 3. Primary unknown cancer Pancreatic cancer 9 5. Pseudomyxoma peritonei Primary acquired melanosis with atypia (topical).

3 *Health Canada approved indication . BC Cancer Drug Manual Page 1 of 7 Mitomycin Developed: September 1994. Revised: 1 April 2018. Mitomycin SPECIAL PRECAUTIONS: Carcinogenicity: Carcinogenic in mice and rats when administered in doses approximating usual therapeutic 2,3. amounts. Mutagenicity: No information found. 3. Fertility: Effect on fertility is not known. 4. Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk ( , if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). 3. Breastfeeding is not recommended due to the potential secretion into breast milk. SIDE EFFECTS: The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug.

4 Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be 10,11. clinically important. ORGAN SITE SIDE EFFECT. Clinically important side effects are in bold, italics 4. blood/bone marrow/ anemia (19-24%) ; hemolytic anemia febrile neutropenia leukopenia (50-79%, severe 11%); within 8 weeks; cumulative thrombocytopenia (40-72%, severe 19%); within 8 weeks; apparent recovery may 3. occur, followed by further depression 4 2. cardiovascular (general) CHF (3-15%) ; with doses >30 mg/m 2,3 4. constitutional symptoms fever (14%). 3,4. malaise ( 10%) ; prolonged dermatology/skin extravasation hazard: vesicant alopecia (1-10%). cellulitis at the injection site; occasionally severe dermatitis (10%); commonly palmar rash with desquamation, typically on the extremities, less often on the trunk and genitals 3.

5 Induration 2,3 3. mucocutaneous toxicity (4%) ; including mouth ulcers, desquamation, and pruritus 4. nail banding/discolouration (>10%). 2,4. rash ( 10%). 12. gastrointestinal emetogenic potential: low 2,3 4. anorexia (14%). diarrhea mucositis 4 3. nausea (14%) ; typically within 1-2 hours and may continue for 2-3 days . BC Cancer Drug Manual Page 2 of 7 Mitomycin Developed: September 1994. Revised: 1 April 2018. Mitomycin ORGAN SITE SIDE EFFECT. Clinically important side effects are in bold, italics 2,4. stomatitis (1-10%). 4 3. vomiting (14%) ; typically within 1-2 hours and subsides rapidly infection septicemia 3. metabolic/laboratory elevated BUN and/or Cr (2%); may be related to cumulative dose; risk increases 3 2. substantially at doses >50 mg/m hypoglycemia 3 4. neurology paresthesia (1-10%). 3. pain injection site pain pulmonary; refer to adult respiratory distress syndrome paragraph following Side bronchospasm Effects table 3,4.

6 Cough ( 7%). 3,4. dyspnea ( 10%). 4. infiltrates (1-10%). 4. pneumonitis (1-10%). renal/genitourinary local irritation (25%); includes cystitis, dysuria, hematuria, increased frequency of 3. micturition, nocturia; dose related; with intravesical 4. renal failure (1%). 3. ulcer at the site of tumour resection, asymptomatic; with intravesical 4. syndromes hemolytic uremic syndrome (HUS)(<1%); see paragraph following the Side Effects table Adapted from standard reference2 unless specified otherwise. 2. Pulmonary toxicity: Typically presents as dyspnea and nonproductive cough. Interstitial infiltrates may or may not 2 2. be present on X-ray. Pneumonitis may be reversed if Mitomycin is discontinued and treatment is instituted early. 2,3. Corticosteroids have been reported to help with symptoms but their therapeutic value has not been determined. Administration of vinca alkaloids to patients who have previously or simultaneously received Mitomycin may cause 2,3.

7 Severe or life-threatening dyspnea and bronchospasm within minutes to hours. Bronchodilators, steroids, and/or 2. oxygen have produced symptomatic relief. In the perioperative setting use only enough oxygen to provide 2. adequate arterial saturation. Cases of adult respiratory distress syndrome have been reported in patients receiving Mitomycin in combination with other chemotherapy and maintained at fraction of inspired oxygen (FiO 2 ). 2. concentrations >50%. Hemolytic Uremic Syndrome consisting of microangiopathic hemolytic anemia, thrombocytopenia, renal failure, 3. and hypertension has been reported. Pulmonary edema, if present, appears to be a particularly grave prognostic factor. HUS is correlated with total dose (single doses 60 mg or cumulative dose 50 mg/m ) and total duration of 3 2. 4. therapy (>5-11 months). These patients typically received long-term (6-12 months) therapy in combination with fluorouracil and doxorubicin; however, some patients received other combinations or were treated for less than six 3.

8 Months. HUS can vary from a chronic course with mild anemia and slowly progressive renal impairment, to a 3. fulminant course with severe anemia, rapid deterioration of renal function, and death. Optimum management has not been established but early treatment with corticosteroids, plasma exchange, plasmapheresis, and/or IV. 3. vincristine have been beneficial in some patients.. BC Cancer Drug Manual Page 3 of 7 Mitomycin Developed: September 1994. Revised: 1 April 2018. Mitomycin INTERACTIONS: AGENT EFFECT MECHANISM MANAGEMENT. 4. vinca alkaloids shortness of breath and unknown may be managed with bronchospasm have been bronchodilators, steroids reported in patients and/or oxygen receiving vinca alkaloids in combination with or after Mitomycin SUPPLY AND STORAGE: Injection: Teva supplies Mitomycin as sterile lyophilized powder in 20 mg single-use vials. Store at room 13. temperature. Protect from light.

9 For basic information on the current brand used at BC Cancer, see Chemotherapy Preparation and Stability Chart in Appendix. SOLUTION PREPARATION AND COMPATIBILITY: For basic information on the current brand used at BC Cancer, see Chemotherapy Preparation and Stability Chart in Appendix. if the product does not dissolve immediately, allow the vial to stand at room temperature until complete dissolution 3. occurs Mitomycin has been added to lidocaine gel immediately prior to intravesicular administration 14. a concentrated solution (2mg/mL) of Mitomycin has been used for intravesicular administration 11,15-17. ; to prevent 18. precipitation, solution should be freshly prepared and not refrigerated Mitomycin Eye Drops: 19-22. Mitomycin eye drops mg/mL ( ) can be prepared with sterile water for injection (SWI). To achieve a mg/mL ( ) eye drop solution: Reconstitute 5 mg vial of Mitomycin with 10 mL SWI to give a concentration of mg/mL.

10 Transfer 6 mL (3 mg) to a sterile 15 mL eye dropper bottle. Add 9 mL SWI to the eye dropper bottle to give a concentration of mg/mL ( ). To achieve a mg/mL ( ) eye drop solution: Reconstitute each of two 5 mg vials of Mitomycin with 10 mL SWI to give a concentration of mg/mL. Transfer 12 mL (6 mg) to a sterile 15 mL eye dropper bottle. Add 3 mL of SWI to the eye dropper bottle to give a concentration of mg/mL ( ). 23,24 23,24. The final product is stable for 2 days at room temperature and 14 days refrigerated. Some data suggest that 23. lowering of the pH below 7 may result in shorter stability. Compatibility: consult detailed reference . BC Cancer Drug Manual Page 4 of 7 Mitomycin Developed: September 1994. Revised: 1 April 2018. Mitomycin PARENTERAL ADMINISTRATION: BC Cancer administration guideline noted in bold, italics Subcutaneous not used due to corrosive nature Intramuscular not used due to corrosive nature 4.