Fluorouracil/calcipotriol cream for solar keratoses and Bowen’s disease

Fluorouracil/calcipotriol is a combination drug for treating solar keratoses and some forms of skin cancer (Cunningham 2017).

After treatment, the area is less likely to develop squamous cell carcinoma—a potentially serious form of skin cancer—for three years (Rosenberg 2019).

Fluorouracil (commercially available as Efudix) has been used successfully for solar keratoses for many years. The combination of fluorouracil and calcipotriol is not commercially available and must be compounded specially.

For convenience, the Spot Check Clinic team refers to the combination as “Efucal” or “FU/Cal”. This is not an official name.

Conditions treated

Solar keratoses

Solar keratoses (also called actinic keratoses or “sunspots”) are patches or crusts on the skin, usually in areas with long term sun exposure. They can appear as single spots or as a group covering an area such as the face, forearms or chest.

If untreated, most solar keratoses are harmless, but a small percentage can progress to squamous cell carcinoma (SCC) which can spread to other parts of the body, causing serious illness and sometimes death.

Intraepithelial carcinoma (Bowen’s disease)

Also known as Bowen’s disease or squamous cell carcinoma in situ. This is a mild and slow-growing form of skin cancer which often appears as a scaly patch of skin. If untreated, it can potentially progress to squamous cell carcinoma.

Treatment alternatives

Many options are available for treating solar keratoses or Bowen’s disease.

Individual solar keratoses can be treated by methods such as:

• Freezing with liquid nitrogen
• “Burning off” with electrosurgery or radiosurgery
• Surgical removal by shaving off or cutting out

Large numbers or areas of solar keratoses usually need field treatment, which treat the whole area (not just the visible solar keratoses) by applying a cream, sometimes with a light to activate it. These treatments work well, but have drawbacks which can make it difficult to complete a course of treatment:

• Inflammation, pain, redness, sores and blisters on the treated area
• Duration of treatment is traditionally several weeks
• Need to avoid sun exposure during treatment
• A single treatment dose is possible using photodynamic therapy, but it is expensive and can be painful.

The “FU/Cal” combination

“FU/Cal” contains two main ingredients:

1. 5-fluorouracil : Also known as 5-FU or Efudix, this drug has been used for many years as an effective treatment for solar keratoses and Bowen’s disease. It is toxic to cancerous and pre-cancerous cells, but has little effect on normal undamaged skin.
2. Calcipotriol : This is a form of vitamin D which stimulates the immune system to attack cancer and pre-cancer cells.

In combination, this treatment has significant advantages over 5-fluorouracil alone:

• The treatment course lasts days rather than weeks
• There is less inflammation and irritation than when 5-fluorouracil is used alone
• The treated area is less likely to develop squamous cell carcinoma for 3 years after treatment (with 5-fluorouracil alone,this benefit lasts only one year).

How to take fluorouracil/calcipotriol

Length of treatment course

Note that the duration of treatment many need to be varied depending on clinical response or side effects.

‍

Application instructions

1. Wash the skin to be treated using lukewarm water. Avoid soap which may sting or irritate your skin, especially as treatment progresses.
2. Pat dry the affected area.
3. Allow your skin to completely dry.
4. Apply a thin layer of cream to the affected area(s)twice a day, without a dressing, for the time advised by your doctor. Do not continue further unless advised by your doctor.
5. Use a non-metal applicator, cotton bud or a rubber glove to apply a thin film of cream to your affected skin. Use the smallest amount that can cover the treatment area.
6. Don’t allow the cream to contact mucous membranes, such as eyes, eyelids, nostrils and lips, unless your doctor has advised you to treat these areas.
7. Do not apply to broken skin or open cuts as it maybe absorbed into the bloodstream and may cause side effects.
8. Wash your hands carefully and thoroughly immediately after using the cream.
9. Do not cover the treated area unless your doctor tells you to.

Apply in the morning and then again in the late afternoon or early evening. Do not apply the cream immediately before going to bed. Apply at least 1.5 – 2 hours before bedtime to enable complete absorption and prevent wiping off on to pillowcases and sheets. Contact with pillowcases or sheets may cause spreading of the cream to normal skin that does not need treatment.

The total area of skin treated with at any time should not exceed 500 cm² (approx.23 x 23cm). Treat larger areas a section at a time.

Precautions

Fluorouracil/calcipotriol must not be used during pregnancy or while breastfeeding.

During the treatment course and while the skin is inflamed or ulcerated following treatment, don’t use cosmetics, moisturisers or other medications unless your doctor has advised you to.

‍

What to expect

Fluorouracil/calcipotriol can be very irritating to the skin, although in most cases the irritation is mild.

The treated area while appear unsightly and may be uncomfortable during treatment and for up to 2 weeks after the course is completed.

Side effects and aftercare

Irritated skin may be itchy or painful. There may be a burning sensation, redness and ulcers or sores in the treated area. Sometimes these symptoms affect areas that did not previously have solar keratoses. This means that the ingredients are treating sun damaged skin that has not yet developed into solar keratoses or skin cancer.

Inflammation and redness usually settles in 2-3 weeks. it may be possible to reduce this time with a course of low-level light therapy., which works well to settle inflammation and redness following surgical procedures and skin injuries such as burns (Min 2013). This treatment is available at Spot Check Clinic.

Do not use antiseptics such as Betadine, as they tend to dry the skin and make irritation and pain worse. If you suspect that the skin has become infected, notify your doctor.

In unusual cases, more general side effects can occur. These include fever, dizziness, abdominal pain and cramps, diarrhoea and vomiting. If you experience any of these symptoms, stop using the medication and notify your doctor.

Storage

Keep the cream stored in the fridge, between 2-8°C.Protect from heat. Fluorouracil/calcipotriol can be stored outside of the fridge at room temperature for up to 48 hours.

Keep all medicine out of the reach of children.

Do not flush unused medications or pour down a sink or drain. Return any unused fluorouracil/calcipotriol to Spot Check Clinic or a pharmacy, especially if it is past the expiry date.

Availability

We prescribe fluorouracil/calcipotriol only to patients who attend Spot Check Clinic in person and have a face-to-face consultation with our specialist skin cancer doctor.

It’s important for an experienced skin cancer doctor (preferably accredited by the Skin Cancer College of Australasia) to examine your skin before prescribing this medication. Because of the risk of side effects, you must be able to return to the prescribing doctor’s clinic at short notice.

The Skin Cancer College maintains a list of accredited doctors with demonstrated competence in the management of skin cancer.

This medication must be dispensed by a specialist compounding pharmacist. If we decide that it’s a suitable treatment for your condition, we send a prescription directly to the compounding pharmacy, who will later contact you to arrange delivery and payment.