TOLAK

Key points

Favourable opinion for reimbursement in the topical treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis (Olsen grade I and II) of the face, ears and/or scalp in adults.

What therapeutic improvement ?

No therapeutic improvement compared to EFUDIX 5 % (5-fluorouracil) cream.

Role in the care pathway ?

The objective of treatment is to destroy the lesions. Regular monitoring is initiated to detect recurrences. The choice of treatment depends on the seriousness of the lesions, the location, contraindications and the prescriber’s habits.

If cutaneous squamous cell carcinoma is suspected, pathology testing of the lesions is necessary before they are treated.

Cryotherapy is the reference treatment in the event of a small number of lesions (≤ 5 lesions). This aggressive, painful method cannot be used in the event of multiple lesions.

Dynamic phototherapy using a sensitising agent is an alternative to cryotherapy, particularly in the event of multiple lesions, of mild to moderate severity (non-hyperkeratotic), and located on the face and/or alopecic scalp, since this enables treatment of all the lesions in a single session, with a good healing result. The sensitising agents with an MA in this indication are methyl aminolevulinate hydrochloride (METVIXIA cream) and 5-aminolevulinic acid (EFFALA medicated plaster and AMELUZ gel, not marketed).

In this clinical situation, METVIXIA is an alternative to first-line cryotherapy.

The other alternatives to cryotherapy in the event of multiple lesions are 5-fluorouracil (5-FU) as a topical treatment (EFUDIX 5 %), imiquimod (ALDARA) and mechanical dermabrasion. Diclofenac (SOLARAZE) is not recommended in the absence of valid demonstration of its efficacy compared to 5-FU and cryotherapy (Opinion of 16/12/2009). CO₂ laser treatment and electrocoagulation and curettage can also be treatment options.

When the lesions are large, surgery is sometimes used, possibly followed by a skin graft if the area to be treated is extensive.

Role of the medicinal product in the care pathway

TOLAK 40 mg/g cream (5-FU, 4 %, 1 application/day) has demonstrated its superiority compared to placebo in terms of the complete disappearance of lesions, with a substantial effect size. However, its non-inferiority compared to the other medicinal product containing the same active substance currently used (EFUDIX 5 % cream, 5-FU 5 %, 2 applications/day) has not been demonstrated. Furthermore, a better tolerability of TOLAK compared to that of EFUDIX has not been demonstrated.

No data are available having compared TOLAK 40 mg/g (5-FU) cream to the other available alternatives.

The Transparency Committee considers that TOLAK 40 mg/g (5-FU) cream is liable to be an alternative to cryotherapy in the event of multiple lesions of non-hyperkeratotic, non-hypertrophic actinic keratosis (Olsen grade I and II) of the face, ears and/or scalp in adults. However, its role in the care pathway cannot be specified compared to the other alternatives available, including 5-FU 5 % (in the absence of demonstration of its non-inferiority compared to this treatment).