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 DNA cross-links, leading to inhibition of DNA synthesis and cell death. It is a key component in the treatment of various solid tumors, particularly in the Indian context for cancers like anal, bladder, and gastric cancers, where it is often used in combination regimens or as an intravesical agent.
| 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 activity, which is not easily repaired. Pharmacological effects persist beyond its measurable plasma concentration. | Poor and variable when given orally (<10%). Primarily administered intravenously (IV) or intravesically, where systemic bioavailability from intravesical instillation is minimal (approximately 10-15%). |
2. Mechanism of Action
Mitomycin is a prodrug that undergoes enzymatic bioreduction (primarily in hypoxic tumor cells) to generate reactive intermediates. These intermediates alkylate DNA, forming covalent cross-links primarily between the N2 position of guanine residues on complementary DNA strands. This cross-linking inhibits DNA synthesis and transcription, leading to single-strand breaks and ultimately, cell cycle arrest and apoptosis.
3. Indications & Uses
- Anal Canal Carcinoma (in combination with 5-fluorouracil and radiotherapy)
- Superficial Transitional Cell Carcinoma of the Urinary Bladder (as intravesical therapy)
- Disseminated Adenocarcinoma of the Stomach or Pancreas (in combination regimens)
4. Dosage & Administration
Adult Dosage: **IV:** Varies by protocol. Common regimens: 10-20 mg/m² as a single dose every 6-8 weeks, OR 2 mg/m²/day for 5 days every 6 weeks. **Intravesical:** 20-40 mg in 20-40 mL of sterile water instilled into the bladder once weekly for 8 weeks, then monthly for up to 1 year. Dose must be individualized based on BSA, hematological parameters, and regimen.
Administration: **IV Use:** Reconstitute 10mg vial with 10-40mL of Sterile Water for Injection. Administer as a slow IV push or short infusion (over 5-20 minutes). **MUST** be given through a free-flowing IV line to avoid extravasation. **Intravesical Use:** Instill via urethral catheter into empty bladder, retain for 1-2 hours. Patient should rotate position every 15 minutes. Avoid concurrent systemic absorption by ensuring no urinary tract trauma.
5. Side Effects
Common side effects may include:
- Myelosuppression (Leukopenia, Thrombocytopenia, Anemia) - Nadir at 4-6 weeks
- Nausea and Vomiting (moderate)
- Anorexia
- Malaise/Fatigue
- Alopecia (mild to moderate)
- Stomatitis
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) | Risk of disseminated infection due to immunosuppression. Contraindicated. | Major |
| Cimetidine | May inhibit hepatic microsomal enzymes, potentially increasing Mitomycin toxicity. Monitor closely. | 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). Additive myelosuppression. | 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 several months after treatment.
- DO drink plenty of fluids unless contraindicated.
- DO NOT receive any vaccinations without consulting your oncologist.
- DO NOT take over-the-counter NSAIDs or aspirin without asking your doctor (increase bleeding risk).
- DO NOT become pregnant or breastfeed during treatment.
8. Toxicology & Storage
Overdose: Exacerbation of all major toxicities: Severe, prolonged myelosuppression (pancytopenia), HUS with microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, mucositis, pulmonary toxicity, and septic shock.
Storage: Store unopened vials at controlled room temperature (15°-25°C), protected 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, protected from light. Solutions for intravesical use should be used immediately after preparation. Do not freeze. Discard any unused portion.