Topical Cytotoxic Agents at a Glance
- Topical and intralesional cytotoxic agents are effective in the treatment of skin cancers and inflammatory and infectious dermatologic conditions.
- They aim for maximum efficacy against cutaneous targets while sparing normal tissue and minimizing systemic toxicity.
- They comprise 5-fluorouracil, nitrogen mustard, carmustine, vinblastine, bleomycin, methotrexate, podophyllin, and miltefosine.
Mechanism of Action and Formulations
Topical 5-fluorouracil (5-FU) has been used in clinical practice since the 1960s. It is a structural analogue of thymine that blocks DNA synthesis by inhibiting thymidylate synthetase (Table 220-1). Topical 5-FU is commercially available as a 0.5% cream carried in a microsphere vehicle, as a 1% solution or 1% cream, as a 2% or 5% solution, and as a 5% cream. The solution can also be used for intralesional injection.
Table 220-1 Topical and Intralesional Cytotoxic Agents Used in Dermatology: Mechanism of Action, Formulation, Main Indications, and Common Side Effects |Favorite Table|Download (.pdf)
Table 220-1 Topical and Intralesional Cytotoxic Agents Used in Dermatology: Mechanism of Action, Formulation, Main Indications, and Common Side Effects
Mechanism of Action
Common Side Effects
Blockage of DNA synthesis by inhibition of thymidylate synthetase
0.5% cream (microsphere vehicle)
1%, 5% cream 1%, 2%, 5% solution
Superficial basal cell carcinomas
Local irritation, erythema, pain, swelling, pruritus, dyspigmentation, allergic contact dermatitis, photosensitivity
Mechlorethamine (nitrogen mustard)
Alkylating activity, immune stimulation
Compounded: 0.01%–0.04% aqueous solution, ointment
Stages IA, IB
Irritant or allergic contact dermatitis, immediate-type hypersensitivity, secondary cutaneous malignancies, dyspigmentation
Alkylation agent: inhibits DNA, RNA, and protein synthesis
Compounded: solution or ointment 10 mg or 20 mg/dL
Stages IA, IB
Myelosupression, leukopenia, erythema, skin tenderness, and telangiectasia
Antimitotic agent: acts by disrupting microtubules, blocking cell division in metaphase
Intralesional injection: 0.1–0.6 mg/mL in saline solution
Local pain, hyperpigmentation
Rarely: mononeuropathy, transient flu-like syndrome
Disrupts DNA synthesis and causes scission of DNA strands
Intralesional injection: 1 U/mL solution
Viral warts, hemangiomas, keloids and hypertrophic scars
Local pain and swelling
Antimetabolite: interferes with DNA synthesis (inhibition of dihydrofolate reductase)
Intralesional injection: 5–75 mg
Hematologic toxicity, hepatotoxicity, nausea, abdominal pain, oral aphthae, reversible alopecia, pancytopenia
Binds tubulin, disrupting the cellular cytoskeleton
Erythema, erosions, tenderness
Cytotoxic: promotes phospholipid turnover and modulates membrane signal transduction by inhibition of protein kinase C
Cutaneous metastases of breast cancer Cutaneous lymphomas
Local: burning, erythema, and fine scaling
5-FU 5% cream has been approved by the US Food and Drug Administration (FDA) since 1970 for the treatment of actinic keratoses in any location and superficial basal cell carcinomas; 5-FU 0.5% cream is FDA approved for treatment of actinic keratoses of the face and anterior scalp. 5-FU is used twice daily ...