Mechlorethamine -Uses

What is Mechlorethamine?

Mechlorethamine (mek” lor eth’ a meen), also known as chlormethine and mustine, is a nitrogen mustard and was the first alkylating agent developed for use as an antineoplastic agent in man. It remains the most reactive in this class of agents. It has been in clinical use for more than 60 years, given systemically in combination with other antineoplastic agents to treat Hodgkin disease, chronic leukemias, lung cancer and polycythemia vera.

Currently, however, it is used largely as a topical gel for therapy of cutaneous T-cell lymphomas and mycosis fungoides. Given parenterally in combination with other antineoplastic agents it was associated with low rates of serum enzyme elevations during therapy, but mechlorethamine has not been implicated specifically in cases of acute, clinically apparent injury.

Identity of Mechlorethamine

Drug Class	Antineoplastic agents, alkylating agents
Brand names	Mustargen®, Valchlor
Synonyms	Chlormethine, Chlormethinum, Clormetina, Mechlorethamine, Mustine, Nitrogen mustard
Molecular Formula	C5H11Cl2N
Molecular Weight	156.054 g/mol
IUPAC Names	bis(2-chloroethyl)(methyl)amine
Structural formula of main components
Pure active ingredient	Mechlorethamine Hydrochloride
Appearance	Liquid, colorless/pale yellow when fresh
Melting point	108-111 °C
Solubility	Very slightly soluble in water
Storage	Store in the freezer at -13°F to 5°F (-25°C to -15°C)
Excretion	Urinary excretion
Available as	Powder for solution, Gel
Prescription	Doctor prescription required

What are the uses of Mechlorethamine?

Mechlorethamine is indicated for use in the treatment of the following conditions:

• Skin cancer (cutaneous T-cell lymphoma)
• Lymphocytic leukemia
• Chronic lymphocytic leukemia
• Mycosis fungal diseases
• Bronchial carcinoma
• Polycythemia vera

Assists in alleviating the symptoms of metastatic carcinoma leading to effusion.

Mechlorethamine is used directly on the skin. When using Mechlorethamine, the drug works to slow or prevent the spread and growth of cancer-causing cells.

Side effects of Mechlorethamine

Important things to remember about the side effects of Mechlorethamine:

• Most people do not experience all of the side effects listed.
• Side effects are often predictable in terms of their onset and duration.
• Side effects are almost always reversible and will go away after treatment is complete.
• There are many options to help minimize or prevent side effects.
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication.

The following side effects are common (occurring in greater than 30%) for patients taking Mechlorethamine:

•  Low blood counts.  Your white and red blood cells and platelets may temporarily decrease.  This can put you at increased risk for infection, anemia and/or bleeding.

• Nausea and vomiting.  Usually occurs within first 3 hours after drug administration.  You will be given anti-nausea medication before receiving drug.
• Hair loss
• Mouth sores
• Darkening of veins used for infusion
• Redness, dryness, irritation with topical use
• Loss of fertility.  Meaning, your ability to conceive or father a child may be affected by mechlorethamine.  Discuss this issue with your health care provider.

These side effects are less common side effects (occurring in about 10-29%) of patients receiving Mechlorethamine:

• Fever
• Diarrhea
• Poor appetite
• Taste changes (metallic taste)
• Ringing in the ears (tinnitus) (see hearing problems)
• Abnormal blood tests: increased uric acid levels

Delayed effects of Mechlorethamine:

• There is a slight risk of developing a blood cancer such as leukemia after taking Mechlorethamine.  Talk to your doctor about this risk.

Mechanism of action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. Mechlorethamine is cell cycle phase-nonspecific.

Food and Drug Interactions

• There are no known interactions of mechlorethamine hydrochloride with food.
• This drug may interact with other medicines. Tell your doctor and pharmacist about all the prescription and over-the-counter medicines and dietary supplements (vitamins, minerals, herbs and others) that you are taking at this time. Also, check with your doctor or pharmacist before starting any new prescription or over-the-counter medicines, or dietary supplements to make sure that there are no interactions.
• The safety and use of dietary supplements and alternative diets are often not known. Using these might affect your cancer or interfere with your treatment. Until more is known, you should not use dietary supplements or alternative diets without your cancer doctor’s help.

Dosing

Dosage Forms & Strengths

Powder for injection: 10mg/vial

Cancers

• Leukemia/Lymphomas/Polycythemia Vera/Mycosis Fungoides/Bronchogenic Carcinoma
• 4 mg/kg IV divided over 2 or 4 days
• Combo treatment (MOPP regimen): 6 mg/m²/day IV days 1 and 8 q4Weeks
• Do not repeat course until WBC >1000/mm³ & platelets >50 k/mm³

Metastatic Carcinoma

• Intracavitary: 0.4 mg/kg once
• Intrapericardial: 0.2 mg/kg once

Mycosis Fungoides (Orphan)

Orphan indication sponsor

• Yaupon Therapeutics, Inc; 259 Radnor Chester Road; Radnor, PA 19087

Administration

Monitor

• CBC, renal, hepatic, & bone marrow functions
• Adjust subsequent dose based on WBC, platelet counts

Other Indication & Uses

• Intrapleural, intraperitoneal, intrapericardial
• Off-label: Cutaneous mycosis fungoides (topical application)

In case of emergency/overdose

In case of overdose, call the poison control center. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your nearby emergency services.

Symptoms of overdose may include the following:

• Fever, chills, sore throat, ongoing cough and congestion, or other signs of an infection
• Unusual bleeding or bruising
• Bloody or black, tarry stools
• Bloody vomit
• Vomited material that looks like coffee grounds

Precautions

• Before starting mechlorethamine treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, or products containing aspirin unless your doctor specifically permits this.
• Do not receive any kind of immunization or vaccination without your doctor’s approval while taking mechlorethamine.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (mechlorethamine may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
• For both men and women: Do not conceive a child (get pregnant) while taking mechlorethamine. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.

Mechlorethamine During Pregnancy or Breastfeeding

Mustargen is not recommended for use during pregnancy. It may harm a fetus. If you become pregnant or think you may be pregnant, tell your doctor. Males and females using this drug should use birth control (e.g., birth control pills, condoms) during treatment; consult your doctor. It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended.