1. Clinical Overview
Mitomycin is a potent antineoplastic antibiotic derived from *Streptomyces caespitosus*. It functions as a bioreductive alkylating agent, requiring intracellular enzymatic activation to form cross-links in DNA, leading to inhibition of DNA synthesis and cell death. It is a key component in the management of various solid tumors and is uniquely used in ophthalmology for glaucoma surgery.
| Onset | Duration | Bioavailability |
|---|---|---|
| Cytotoxic effects begin within hours of administration, but clinical tumor response may take several weeks to become evident. | The cytotoxic effect is prolonged due to its DNA cross-linking, which is not easily repaired. Hemotoxicity (myelosuppression) is delayed and cumulative, with nadir typically occurring 4-8 weeks after a dose. | Not applicable for intravenous use (100% bioavailable). For intravesical use in bladder cancer, systemic absorption is minimal (<10%) with intact bladder mucosa. |
2. Mechanism of Action
Mitomycin is a prodrug that requires enzymatic bioreduction (via NADPH-cytochrome c reductase, DT-diaphorase) in hypoxic tumor cells to generate reactive intermediates. These intermediates act as bifunctional or trifunctional alkylating agents, forming covalent cross-links primarily between the N-2 positions of adjacent guanine residues on complementary strands of DNA. This inhibits DNA synthesis and transcription, leading to single-strand breaks and cell cycle arrest, predominantly in the late G1 and S phases.
3. Indications & Uses
- Adenocarcinoma of stomach or pancreas (as part of combination therapy)
- Superficial Transitional Cell Carcinoma (TCC) of the Urinary Bladder (intravesical instillation)
- Anal Cancer (in combination with 5-Fluorouracil and radiotherapy)
- Prevention of fibrosis/scarring in Glaucoma Filtration Surgery (Mitomycin C-soaked sponges applied intraoperatively)
4. Dosage & Administration
Adult Dosage: **IV:** 10-20 mg/m² as a single dose every 6-8 weeks. Commonly 10 mg/m². Dose is part of a combination regimen. **Intravesical:** 20-40 mg in 20-40 mL sterile water instilled into the bladder weekly for 8 weeks, then monthly for up to 1 year. **Ophthalmic (Surgery):** 0.2-0.4 mg/mL solution applied via soaked sponge for 2-5 minutes, followed by copious irrigation.
Administration: **IV Route:** Reconstitute with Sterile Water for Injection. Administer as a slow IV push or short infusion (5-10 minutes) through a **freely flowing IV line**. **EXTRAVASATION HAZARD:** Must be administered by personnel trained in handling vesicants. **Intravesical:** Patient should restrict fluids prior, instil drug, retain for 1-2 hours, reposition every 15 minutes, then void.
5. Side Effects
Common side effects may include:
- Myelosuppression (Leukopenia, Thrombocytopenia - delayed and cumulative)
- Nausea and vomiting (moderate)
- Anorexia
- Malaise/fatigue
- Alopecia (mild to moderate)
- Local tissue damage/necrosis on extravasation
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Other Myelosuppressive Agents (e.g., Doxorubicin, Cyclophosphamide) | Additive bone marrow toxicity. Increased risk of severe leukopenia/thrombocytopenia. | Major |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of disseminated infection due to immunosuppression. Vaccination contraindicated. | Major |
| Cimetidine | May inhibit hepatic microsomal enzymes, potentially increasing Mitomycin toxicity. | Moderate |
| Vitamin K Antagonists (Warfarin) | Increased risk of bleeding due to thrombocytopenia and possible interference with coagulation. | Moderate |
| Radiotherapy | Enhanced toxicity in irradiated fields (recall phenomenon). Increased risk of pulmonary toxicity. | Major |
7. Patient Counselling
- Do report any signs of infection (fever, chills, sore throat) immediately.
- Do maintain good oral hygiene to reduce risk of stomatitis.
- Do use effective contraception during and for at least 6 months after treatment.
- Do not receive any live vaccinations without consulting your oncologist.
- Do not conceive or father a child during treatment.
- For intravesical therapy: Void completely after the prescribed retention time and wash genital area to prevent skin irritation.
8. Toxicology & Storage
Overdose: Exacerbation of all major toxicities: Severe, prolonged myelosuppression (pancytopenia), renal failure, HUS, pulmonary edema/interstitial pneumonitis, myocardial damage, and septic shock.
Storage: Store unopened vials at 2°C to 8°C (refrigerated). Protect from light. Reconstituted solution with Sterile Water for Injection is stable for 14 days under refrigeration (2-8°C) or 7 days at room temperature (15-25°C) if protected from light. Solutions for intravesical use should be used immediately after preparation. Do not freeze.