Chemotherapy for Skin Cancer

Reviewed by: HU Medical Review Board | Last reviewed: May 2025 | Last updated: May 2025

Chemotherapy kills or damages rapidly dividing cells. This means that chemotherapy is toxic to cancer cells, which divide rapidly and out of control. However, chemotherapy also affects rapidly dividing healthy cells. Examples include healthy blood cells, hair cells, and the mucous membranes that line the mouth, throat, and digestive system.1

Newer immunotherapies and targeted therapies are generally more effective than chemotherapy for treating melanoma. Their side effects may be less severe. Therefore, chemotherapy is not used as often now for skin cancer. Nevertheless, it may still be used to treat some skin cancers, especially if other drugs are not working.2

How is chemotherapy given?

Chemotherapy may be used alone or in combination with other treatments. Typical combinations are chemotherapy with immunotherapy or with radiation therapy. The US Food and Drug Administration (FDA) has approved some chemotherapy drugs for certain cancers. However, when treating cancer, it is also common to use approved chemotherapy drugs “off-label,” which means for unapproved uses.3

Systemic chemotherapy

Systemic (whole body) chemotherapy is often given by injection into a vein (intravenous) or under the skin (subcutaneously). It may also be taken by mouth in pill form.1

Systemic chemotherapy travels throughout the body via the bloodstream. Systemic chemotherapy can be used as a primary treatment to kill cancer cells that have spread to distant parts of the body (metastasized).1

Systemic chemotherapy is also used as adjuvant therapy. Adjuvant therapy is an additional cancer treatment that is given after the primary (main) treatment. Adjuvant therapy can help lower the risk that the cancer comes back. Adjuvant systemic chemotherapy may be used after surgery to kill any remaining cancer cells.1

Another use for systemic chemotherapy is treating cancer that cannot be removed with surgery. One example would be tumors that have grown around major nerves or blood vessels. Another example is cancer that is so widespread that it is not possible to remove all the tumors.4

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Isolated limb perfusion

When melanoma is only in the arm or leg, it may be possible to just treat that limb with chemotherapy.2,4

The limb is “isolated” from the rest of the body with a tourniquet. A tourniquet is a band or device that prevents blood flow in or out of the limb. The major blood vessels are also clamped.2,4

Tubes are inserted into the major artery and vein. Blood in the affected limb is routed through a machine. The machine heats the blood and infuses (puts) chemotherapy into it. Melphalan is a drug commonly used for this procedure.2,4

The drug circulates through the limb for 60 to 90 minutes. Before the doctor restores normal blood flow, the limb is cooled, and the remaining medicine is flushed out.2,4

Intralesional therapy

Chemotherapy drugs can be injected directly into a tumor. This is called intralesional therapy. Intralesional therapy is used to treat Kaposi sarcoma (KS). Vinblastine may be used for intralesional treatment of KS.5

Topical chemotherapy

5-Fluorouracil (5-FU) is a topical chemotherapy drug. Topical means that the medicine is applied to the skin. When fluorouracil is applied to the skin, it kills tumor cells on the skin surface. 5-FU is only used to treat actinic keratosis and certain forms of basal cell carcinoma and squamous cell carcinoma.6

Tirbanibulin (Klisyri®) is another topical chemotherapy drug that is used to treat actinic keratoses on the face or scalp.6

What types of skin cancer does chemotherapy treat?

Chemotherapy can be used to treat the following types of skin cancer.

Advanced melanoma

Chemotherapy is one option for treating advanced melanoma, for example:4

  • Treatment for widespread metastatic melanoma, if other drugs are not working
  • Primary treatment for metastatic melanoma confined to the arm or leg
  • Adjuvant treatment for certain advanced melanomas after the lymph nodes and skin tumor have been removed with surgery
  • Melanoma that has returned (recurred) and started to spread

The chemotherapy drugs used to treat melanoma include:2,4

  • Dacarbazine (DTIC)
  • Temozolomide (Temodar®)
  • Nab-paclitaxel (Abraxane®)
  • Paclitaxel (Taxol™)
  • Cisplatin (Platinol®)
  • Carboplatin (Paraplatin®)

Outcomes after chemotherapy for melanoma have been disappointing, which is why it is used less often nowadays.2,4

Kaposi sarcoma

Chemotherapy can potentially weaken the immune system. Therefore, it can be challenging to use chemotherapy in those with immune system problems, such as HIV/AIDS. Nevertheless, with careful treatment planning, chemotherapy may be used to treat Kaposi sarcoma (KS).5,7

Chemotherapy may be injected directly into tumors, such as those in the mouth. It may be used systemically if the cancer is widespread. The chemotherapy drugs used to treat KS include:7

  • Liposomal doxorubicin (approved for KS) (Doxil®, Lipodox®)
  • Paclitaxel (approved for KS) (Taxol™)
  • Vinblastine (approved for KS) (Velban®)
  • Gemcitabine (Gemzar®)
  • Vinorelbine (Navelbine®)
  • Bleomycin (Blenoxane®)
  • Etoposide (Vepesid®)

Merkel cell carcinoma

Systemic chemotherapy has been used to treat Merkel cell carcinoma (MCC). It can shrink or slow the spread of MCC tumors for some time. There are also reports of intralesional chemotherapy with bleomycin for early MCC. Because MCC is so rare, it has been hard to study chemotherapy. It is not clear how well it works and which patients have the best response.8

No chemotherapy drugs have been approved specifically for MCC. However, drugs used to treat MCC include:8

  • Cisplatin (Platinol®)
  • Carboplatin (Paraplatin®)
  • Etoposide (Vepesid®)
  • Topotecan (Hycamtin®)

Non-melanoma skin cancer

Squamous cell carcinoma (SCC) rarely spreads beyond the skin tumor. However, chemotherapy is 1 option for SCC that has spread. In this situation, chemotherapy may be combined with radiation therapy.9

Not much information is available about chemotherapy for advanced SCC or basal cell carcinoma. Chemotherapy medications that may be used for SCC include:9

  • Cisplatin (Platinol®)
  • Carboplatin (Paraplatin®)
  • Paclitaxel (Taxol™)
  • 5-Fluorouracil (5-FU)

What are the side effects of chemotherapy?

Systemic chemotherapy is usually given in cycles. You may need to stay in the hospital during treatment. This is done to manage the side effects of the drugs.1

Systemic chemotherapy causes side effects throughout the body. Typical side effects of chemotherapy include:1,4,9

  • Hair loss
  • Mouth sores, taste changes, dry mouth
  • Loss of appetite
  • Nausea and vomiting
  • Diarrhea or constipation
  • Infection
  • Bleeding problems and easy bruising
  • Anemia and fatigue
  • Memory changes
  • Nerve changes, including numbness, tingling, burning, or weakness
  • Pain
  • Fluid retention and swelling
  • Changes in sexual function and fertility

Many side effects can be prevented or managed. For example, blood transfusions can correct low blood cell levels. You can take drugs for nausea and vomiting. You may also take antibiotics and antifungals to prevent infection. Side effects vary among specific chemotherapy drugs, and your provider will manage them accordingly.1

Some people try complementary medicine to relieve chemotherapy side effects. You may find that meditation or hypnosis reduces stress during procedures or treatment. Discuss any complementary medicine you are considering with your doctor. Herbal medicine, vitamins, minerals, and other supplements can interact with your medications. They may reduce the effect of the medication. The interaction could lead to unsafe side effects.

Treatment results and side effects can vary from person to person. This treatment information is not meant to replace professional medical advice. Talk to your doctor about what to expect before starting and while taking any treatment.