Topical nitrogen mustard

What is nitrogen mustard?

Nitrogen mustard (also known as mechlorethamine or mustine) belongs to a class of drugs known as alkylating agents. These agents slow or stop the growth of cancer cells in the body. Nitrogen mustard powder for injection is administered intravenously to treat certain types of cancers, however topical formulations of nitrogen mustard can be prepared to treat cutaneous T-cell lymphomas, namely mycosis fungoides.

Topical preparations of nitrogen mustard are formulated by mixing the injectable powder with either water or an ointment base. The water preparation is unstable and needs to be used immediately, whereas ointment based preparations of nitrogen mustard are stable for at least a few months. A 0.016% gel (US trade name Valchlor™ from Actelion Pharmaceuticals).

How does topical nitrogen mustard work?

Nitrogen mustard belongs to the group of alkylating agents that also include cyclophosphamide, ifosfamide, melphalan, chlorambucil and carmustine (BiCNU). Nitrogen mustard and carmustine can be used topically to treat cutaneous lymphomas. The mechanism of action is still uncertain.

What is topical nitrogen mustard used for?

Topical nitrogen mustard has been used for the treatment of mycosis fungoides since the 1950s. It is particularly effective in patch or plaque stage mycosis fungoides. Complete response rates have been achieved in 76-80% of patients with limited patch/plaque (stage IA) and 35-68% in those with generalised patch/plaque (stage IB). It is also used for the treatment of Langerhans cell histiocytosis.

How to use topical nitrogen mustard?

There are several different regimes. Topical nitrogen mustard (either a water-based preparation, a gel, or an ointment-based preparation) may be applied daily until lesions resolve completely. This may be followed by a time of maintenance therapy for about 1-2 months.

The following general measures should be carried out when applying topical nitrogen mustard.

• First, apply a small amount of nitrogen mustard to a selected test patch (palm-size) on your skin once a day for 7-10 days. If there is no significant irritation, new rash, redness or itching you can then start to apply the nitrogen mustard preparation as directed by your doctor to lesions.
• Usually, topical nitrogen mustard is applied once daily after showering or in the evening. Apply sparingly to the affected areas; the nitrogen mustard is usually absorbed into the skin within the first hour after application.
• Allow to dry before covering with clothing. Do not wash for 4 hours after application.
• Disposable nitrile gloves may be worn to apply the preparation or alternatively apply directly with your hands and wash thoroughly afterwards.
• Additional moisturising lotions or creams may be applied throughout the day as necessary.

Precautions when using nitrogen mustard

Do not apply nitrogen mustard on sensitive areas such as the face and genitals. The risk of developing secondary skin cancers is increased in patients who have received multiple skin treatments, such as phototherapy or radiation in addition to topical nitrogen mustard. Topical nitrogen mustard should be used with caution in pregnant or breastfeeding women. It is reported to cause fetal harm.

Take care to avoid applying topical nitrogen mustard to the eyes (if this occurs irrigate for at least 15 minutes with copious water or normal saline and seek medical attention). Exposure of other mucous membranes such as nostrils, mouth, genitals and anus, should likewise be avoided.

Nitrogen mustard is a probable carcinogen. This means it may cause skin cancer. Protect from sun exposure.

Make sure there is no skin contact with another individual while topical nitrogen mustard is applied.

Stop applying topical nitrogen mustard if the treated areas erode, ulcerated, blister or develop severe redness and swelling. When recommencing treatment, apply it less often, eg every 3 days.

Side effects of nitrogen mustard

The most common side effect of nitrogen mustard is an allergic reaction that usually results in itching, rash, or redness (contact dermatitis). Anaphylaxis has been reported but is rare. This is especially a problem in more sensitive areas such as skin folds and occurs whether an aqueous solution or ointment preparation is used. In most cases, a reduction in the frequency of application or decrease in concentration will lessen the side effects and allow continuation with the medication. Darkening of the skin in the area where the nitrogen mustard was applied may also occur; this is reversible once the medication is stopped.