Mitomycin (Datisan) or Mitomycin C is one of the oldest chemotherapeutic drugs that is still used in the treatment of advanced gastric, pancreatic, cervical, anal, and vulvar cancer.

Mitomycin (Datisan) Uses:

• Gastric cancer:

  • It is helpful in the treatment of disseminated adenocarcinoma of the stomach (in combination with other chemotherapy agents) and as a palliative treatment when other modalities have failed.

• Pancreatic cancer:

  • Treatment of disseminated adenocarcinoma of the pancreas (in combination with other chemotherapy agents) and as a palliative treatment when other modalities have failed.
  • Limitations of use: It is not proposed for single-agent primary therapy or to replace appropriate surgery and/or radiotherapy in the treatment of such conditions.

• Off Label Use of Mitomycin in Adults:

  • Anal cancer
  • Bladder cancer
  • recurrent or metastatic cervical cancer,
  • Advanced esophageal cancer
  • Hepatocellular carcinoma (chemoembolization)
  • Advanced vulvar cancer

Mitomycin Dose in Adults:

Mitomycin (Datisan) Dose in the treatment of Anal carcinoma (off-label):

• 10 mg/m² as an IV bolus on days 1 and 29 (maximum: 20 mg/dose) in combination with fluorouracil and radiation therapy or
• 12 mg/m² on day 1 only in amalgam with fluorouracil and radiation therapy or
• 15 mg/m² on day 1 only in combination with fluorouracil and radiation therapy or
• 10 mg/m² on day 1 (maximum dose: 15 mg) in combination with capecitabine and radiation therapy or
• 12 mg/m² on day 1 (maximum dose: 20 mg) in combination with capecitabine and radiation therapy.

Mitomycin (Datisan) Dose in the treatment of Bladder cancer (off-label):

• Muscle invasive:

  • 12 mg/m² on day 1 (in combination with fluorouracil and radiation).

• Nonmuscle invasive (off-label route): Intravesicular instillation:

  • Low risk of recurrence (uncomplicated):
    • 40 mg as a single dose postoperatively.
    • retain the drug in the bladder for 1 to 2 hours.
  • Increased risk of recurrence:
    • 20 mg weekly for 6 weeks, in continuation with 20 mg monthly for 3 years;
    • need to retain in the bladder for 1 to 2 hours or
    • 40 mg weekly for 6 weeks (with urine alkalinization and decreased urine volume to increase drug concentration);
    • hold on to in the bladder for 2 hours.

Mitomycin (Datisan) Dose in the treatment of recurrent or metastatic Cervical cancer:

• IV: 6 mg/m² on day 1 once every 4 weeks (in union with cisplatin) for a minimum of 2 cycles (preferably 9 cycles).

Mitomycin (Datisan) Dose in the treatment of advanced Esophageal cancer, (off-label):

• IV: 7 mg/m² (maximum dose: 14 mg) once every 6 weeks for 4 cycles (in combination with cisplatin and fluorouracil).

Mitomycin (Datisan) Dose in the treatment of Gastric cancer:

• IV: 20 mg/m² once every 6 to 8 weeks

• Off-label dosing:

  • IV: 7 mg/m² (maximum dose: 14 mg) once every 6 weeks for 4 cycles (in union with cisplatin and fluorouracil).

Mitomycin (Datisan) Dose for chemoembolization in the treatment of Hepatocellular cancer:

• Conventional transcatheter arterial chemoembolization (cTACE):

  • Intra-arterial:
    • 10 mg as a single dose via intra-arterial injection;
    • keeping in view clinical judgment, it may be repeated at 6 to 8-week intervals or
    • 8 mg/m² as a single dose via intra-arterial injection every 4 weeks for at least 2 doses.
    • It can be referred to as protocol and institutional policies for additional dosing/administration details.

Mitomycin (Datisan) Dose in the treatment of Pancreatic cancer:

• IV: 20 mg/m² once every 6 to 8 weeks

Mitomycin (Datisan) Dose in the treatment of advanced Vulvar cancer:

• IV: 15 mg/m² on day 1 every 14 days for 2 cycles (in combination with concomitant radiation and fluorouracil).

Use in Children:

The safety and efficacy of the drug in children have not been established.

Mitomycin (Datisan) Pregnancy Risk Category: X

• In animal reproduction studies, however, adverse events are taken into consideration.

Use of mitomycin during breastfeeding

• It is not known if breast milk contains mitomycin.
• The manufacturer does not recommend breastfeeding because of the risk of serious adverse reactions in breastfed babies.

Mitomycin (Datisan) Dose in Kidney Disease:

• The manufacturer’s labeling states to put down its usage in patients with serum creatinine >1.7 mg/dL, though no other dosage modifications are provided.

• The following adjustments have been recommended (Aronoff 2007):

  • CrCl <10 mL/minute:
    • Lessen dose to 75% of the usual dose.
  • Continuous ambulatory peritoneal dialysis (CAPD): 
    • The dose needs to be reduced to 75% of the usual dose.

Mitomycin (Datisan) Dose in Liver disease:

However, there are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Common Side Effects of Mitomycin (Datisan):

• Gastrointestinal:

  • Anorexia
  • Nausea
  • Vomiting

• Hematologic & oncologic:

  • Bone marrow depression
  • Hemolytic-uremic syndrome
  • Thrombotic thrombocytopenic purpura

• Miscellaneous:

  • Fever

Less Common Side Effects of Mitomycin (Datisan):

• Dermatologic:

  • Alopecia

• Gastrointestinal:

  • Mucous membrane disease
  • Stomatitis

• Renal:

  • Increased serum creatinine

Contraindications to Mitomycin (Datisan):

• Hypersensitivity to mitomycin and any component of the formula
• Thrombocytopenia
• coagulation disorders or other increased bleeding tendencies.

Warnings and precautions

• Bladder fibrosis, and contraction

  • Bladder fibrosis, and contraction have been included with intravesical administration (unlabeled route).

• Suppression of bone marrow: [US Boxed Warning]

  • It is common to experience bone marrow suppression (thrombocytopenia or leukopenia).
  • WBC and platelet loss usually occur within 4 weeks. However, they may occur up to 8 weeks. Recovery occurs in 10 weeks.
  • However, sepsis has been linked to fatalities.
  • Keep an eye out for infection.
  • Myelosuppression can be dose-limiting, delayed in onset and cumulative.
  • Therefore, it is important to monitor blood counts for at least 8 weeks after treatment.
  • Treatment delay or dosage adjustment may need to be made for severe thrombocytopenia (platelets >100,000./mm3), leukopenia, WBC 4,000/mm3), or progressive declines in either of these values.

• Extravasation

  • Mitomycin is an effective vesicant.
  • Before and during infusion, ensure proper placement of the needle or catheter. Avoid extravasation.
  • It can cause tissue sloughing and necrosis.
  • Reports of delayed erythema or ulceration have been made.

• Heart Failure:

  • The American Heart Association's scientific statement states that mitomycin may cause either reversible or exacerbate underlying myocardial dysfunction (magnitude moderate).

• Hemolytic-uremic Syndrome: [US Boxed Warn]

  • Hemolytic-uremic Syndrome (HUS), has been reported (incidence not determined).
  • This condition can include microangiopathic hemolytic Anemia (hematocrit =25%) and thrombocytopenia =100,000./mm3. Irreversible renal failure (serum Creatinine >=1.6 mg/dL).
  • HUS can occur with either single-agent therapy or combination therapy. It is most commonly associated with single doses greater than 60 mg. Blood transfusions may also be an option.
  • Other, less common causes of pulmonary edema, hypertension, and neurologic abnormalities may also be involved.
  • High mortality rates have been reported from HUS.

• Toxicity in the lungs:

  • Patients receiving mitomycin and other chemotherapy were kept at FIO levels >50% perioperatively in cases of severe respiratory distress syndrome (ARDS).
  • Be careful to ensure that you only provide enough oxygen to maintain arterial saturation.
  • Also, dyspnea and nonproductive cough have been described as pulmonary toxicity. A radiograph may also show pulmonary infiltrates.
  • If pulmonary toxicity is observed and other possible causes have been ruled, the therapy may be stopped.

• Renal impairment

  • If serum creatinine levels are >1.7 mg/dL, you don't need to administer.
  • Monitor for signs of renal toxicity.

Mitomycin (systemic): Drug Interaction

Monitoring parameters:

• Monitor CBC with differential (repeatedly during therapy and for ≥8 weeks following therapy).
• monitor for signs and symptoms of HUS.
• serum creatinine
• pulmonary function tests
• monitor infusion site.

How to administer Mitomycin (Datisan)?

• You can administer IV via a slow IV push/bolus or a freely-running, saline injection. Consider using a central vein catheter.
• It acts as a vesicant. It is important to ensure that the catheter or needle are correctly placed prior to and during infusion. However, extravasation should not be allowed.

• Extravasation management

  • Infusions should be stopped immediately. Extravasation can be prevented by leaving the needle/cannula in place.
  • Lift the extremity, and gently aspirate any extravasated solution. Do NOT flush the line.
  • Start dimethyl sulfate antidote (DMSO).
  • Apply a dry, cold compress for 20 mins four times per day for up to two days.

• DMSO

  • Topically apply to the affected area twice per hour for 7 days. Do not cover it with a dressing.

• Intravesicular (off-label route):

  • Infuse the bladder and retain for 1 to 2 hours.
  • Rotate the patient every 15 to 30 minutes.

• Intra-arterial:

  • Transcatheter arterial chemoembolization (TACE; off-label use)
• For conventional TACE, mitomycin was administered with lipiodol and contrast media followed by particle embolization with an embolic agent or
• followed by starch microspheres for vessel occlusion.
• IV antibiotics were administered earlier to the procedure and embolic material was injected through the catheter until hemostasis was achieved.
• Refer to protocol and institutional policies for additional administration details.

Mechanism of action of Mitomycin (Datisan):

• Mitomycin alkylates DNA, producing DNA cross-linking (mainly using guanine or cytosine pairs), and inhibits DNA andRNA synthesis.
• Although it is not specific to cell cycles, it has the greatest effect on cells in late G or early S phases.

Metabolism:

• Primarily hepatic

Half-life elimination:

• 17 minutes (30 mg dose)

Excretion:

• Feces (primarily)
• Urine

International Brands of Mitomycin:

• Mutamycin
• Ametycine
• Baxmicin
• Datisan
• Minazol
• Mitocin
• Mitocyna
• Mitomicina
• Mitomicina-C
• Mitomycin
• Mitomycin C
• Mitomycin-C
• Mitomycin-C Kyowa
• Mitomycine
• Mitonco
• Mitostat
• Mitotie
• Mixandex
• Mutamycin
• Mytomycin C
• Mytoxid
• Riptam
• Vesimycin
• Vetio

Mitomycin Brand Names in Pakistan:

No Brands Are Available in Pakistan.