Pharmacologic therapies for non-melanoma skin cancer are distinguished between “topical” and “systemic” therapies.

Topical therapies are local, on-site therapies, where medication is applied in the form of ointments, creams or gels directly over the tumor.

With systemic therapy, medication is absorbed into the body through either the gastrointestinal tract (via oral medication) or through the surroundings of the gastrointestinal tract, termed parenteral entrance (via injection or infusion). Due to this mechanism, the administered drugs do not act on only a specific location of the body, but instead, they affect the entire organism.

Systemic pharmacologic therapies take a long time (several months to years) to yield results. However, their cosmetic outcome is often much better. These therapies can be administered to combat large, invasive and metastatic tumors, whereas surgical treatments are limited to smaller, localized tumors.

The agent diclofenac, known as an analgesic, is part of the cycooxygenase-2 inhibitor (COX2) group, which inhibits the formation of pain and inflammation. In this gel, diclofenac is combined with hyaluronic acid. The hyaluronic acid in the gel delays the absorption of diclofenac through the skin, so that the active substance accumulates in the upper layer of the skin. The high concentration of diclofenac in the skin, gives rise to stagnated tumor growth in the upper skin layer. The gel of these two ingredients is applied twice a day, over several months on the affected area. In about 50-80% of the cases, a complete regression of the actinic keratosis is achieved.e affected place. In about 50-80% of the cases, a complete regression of the actinic keratosis is achieved.

The ingenol mebutate gel (Picato®) is used to treat specific forms of actinic keratosis. This medication exists in two strengths: 150 microgram/gram or 500 microgram/gram. The active component originates from the plant “petty spurge”, elsewhere known as “cancer weed” or “milkweed” (Euphorbia peplus). An area of 5 x 5 cm can be treated with a single tube of gel. In the year 2013 the German Institute for Quality and Economic Feasibility (IQWiG) attempted to prove that actinic keratosis could be treated better by administering ingenol mebutate gel rather than administering diclofenac-hyaluronic acid gel. Unfortunately, due to the lack of relevant data available to answer the question, no conclusion could be drawn.

Treatment of actinic keratosis using ingenol mubutate gel is done by applying the gel over 2 to 3 consecutive days, directly on the affected skin area. Due to the delayed patient response time associated with this therapy, a patient’s response to the treatment can only be determined approximately 2 months after the therapy has been completed.

Superficial basal cell carcinoma (in-situ) and actinic keratosis can be treated with the chemotherapeutic (cytotoxic agent) 5-Fluorouracil. This therapy prevents cell division, and therefore, the growth of the tumor. Generally, this cream is applied twice a day directly on the tumor tissue. The length of time the treatment course lasts is often between 6 to 10 weeks. This time period can be debilitating for the patient, because side effects of the therapy may include painful irritations with vesication (blistering) and skin erosion (skin damage).

The active ingredient imiquimod is able to activate the body’s own immune system.

After the cream is applied, a local inflammatory response (redness, swelling, pain) can occur at first that is, in some cases, severe. Via a signalling pathway in the immune system, the active ingredient causes an increased number of so-called plasmacytoid dendritic cells (pDCs) to be called into this inflamed tissue. 

These special immune cells react in turn to the imiquimod by releasing increased amounts of interferon alpha, a protein substance that is very effective against viruses and tumours. In addition, this stimulates the pDCs to produce more cell-dissolving proteins, which then also attack the tumour cells and cause the death of those cells.

The application of the imiquimod cream takes place over a period of at least 6 weeks and up to 4 months, and must be carried out under strict and close medical supervision, because it is of paramount importance that the cream is applied regularly.

The active ingredient vismodegib (Erivedge®) has the property of binding to a protein found on the cell membrane (Smoothened) and, in the affected cells, preventing the reading of the genetic information (genes) involved in the tumour growth. This can slow tumour growth. In some cases the tumour shrinks or even disappears completely.

The active ingredient is used in the treatment of symptomatically metastatic basal cell carcinoma or locally advanced basal cell carcinoma for which surgery or radiotherapy is not suitable. This drug has been available in Germany since July 2013.

The treatment duration is mainly based on the course of the disease and the tolerability of the therapy. It can be assumed that therapy will take several months. Use should only be discontinued in consultation with a physician.

Treatment with vismodegib can be very physically demanding. Possible side effects include  muscle cramps, hair loss, weight loss, nausea and vomiting, diarrhoea or constipation, and a change or even loss of the sense of taste.

Severe cases of inoperable, metastatic spinalioma can be treated with the active ingredient methotrexate either as monotherapy or in combination with other cytostatics.

Through monotherapy with methotrexate, the cancer can be successfully treated up to 20-40% of the time (remission rate). With a combination therapy, the rate is considerably higher at 50-90%. In very advanced stages (stage III and IV), the probability of tumour recurrence is 80%.

The treatment duration is mainly based on the course of the disease and the tolerability of the therapy. Of therapy lasting several months. Use should only be discontinued in consultation with a physician.

Therapy with methotrexate can be very physically demanding. Possible side effects include nausea, vomiting, diarrhoea, gastrointestinal bleeding, increased susceptibility to infection, hair loss, blood count disorders, and damage to the liver, kidneys and bladder.