SkinCancerNet Article
Chemotherapy: What Every Patient Should Know

Chemotherapy is the use of cancer-fighting medications to stop the growth of malignant cells. It works by either killing the cells or preventing them from dividing. When treating skin cancer, chemotherapy may be topical (applied to the skin) or systemic (taken by mouth or injected).

Topical Chemotherapy
Topical chemotherapy is used to treat non-melanoma skin cancer that is limited to the top layer of skin. It also is used to treat actinic keratoses (AKs), lesions that can develop on skin that has received years of sun exposure. AKs have the potential to progress to squamous cell carcinoma, a type of skin cancer. Actinic keratoses are also called “solar keratoses.”

A topical chemotherapy medication that dermatologists prescribe is fluorouracil, commonly called 5-FU. 5-FU is applied by the patient as directed, usually twice a day for several weeks. The medication works to erode cancerous and pre-cancerous lesions, and intense skin irritation can occur. Due to skin irritation, the patient may be instructed to use cycle therapy — a form of treatment in which the medication is applied for a specified duration, stopped for a pre-determined amount of time, and then resumed.

Systemic Chemotherapy
Systemic chemotherapy may be part of the treatment plan when skin cancer has metastasized (spread) or the risk of metastasis is high. When treating skin cancer, chemotherapy may be administered:

  • After surgical removal of the tumor if the potential for metastasis is likely

  • To treat metastatic skin cancer that cannot be surgically removed

When administered after surgery, the chemotherapy is called “adjuvant chemotherapy.” The purpose of an adjuvant therapy is to increase the effectiveness of the primary therapy. When chemotherapy is used after surgical removal of the tumor, the purpose is to kill undetected cancerous cells.

When treating metastatic skin cancer, the goal of chemotherapy is either 1) remission or 2) to ease symptoms for a patient with advanced, and probably incurable, cancer.

The form of chemotherapy given depends on the stage, site(s) of the tumor(s), and patient’s ability to tolerate side effects. Systemic chemotherapy may involve the use of a single anti-cancer medication or the combination of two or more medications. When the area to be treated is a limb, isolated limb perfusion or isolated limb infusion may be used.

Isolated limb perfusion (ILP) is a type of chemotherapy used to treat:

  • Recurrent metastatic melanoma

  • Multiple aggressive metastatic tumors of the lower limbs (legs) that cannot be surgically removed

ILP involves an operation on the blood vessels and is used to treat metastatic tumors when the area to be treated can be surgically isolated from the rest of the body. To perform an ILP, the surgeon creates a temporary arterial-venous loop that disconnects the limb’s blood circulation from the rest of the body. A tube is inserted into the arterial-venous loop in order to inject a high-dose of the chemotherapeutic medicine(s). This high dose, which would cause severe side effects without limb isolation, can be given because the anti-cancer medications cannot reach the general circulation. The high dose is given to increase the “kill rate.”

During ILP, a radioisotopic tracer is usually used to monitor the precise flow of the anti-cancer medication(s) to the tumor site(s). A heating unit is typically used to warm the medication(s) before it is placed into the arterial-venous loop, and a warming blanket keeps the tissue receiving the chemotherapeutic medication at a constant temperature. Some studies have shown that warming the anti-cancer medication increases its anti-tumor activity.

The chemotherapeutic medication most often used during ILP is melphalan, which works by binding together the DNA in cancer cells and leads to the cell death. Melphalan may be used alone or combined with another anti-cancer agent, such as nitrogen mustard, cisplatin, or dacarbazine.

Studies have shown that in a substantial number of patients, ILP can achieve complete remission of tumors in the treated leg and may eliminate the need for limb amputation. However, metastatic disease recurs in a substantial number of patients after ILP, and ILP has not been shown to increase overall survival of patients with metastatic melanoma.

A newer form of limb isolation is undergoing evaluation in U.S. clinical trials. It is called isolated limb infusion (ILI). It is used to treat advanced melanoma confined to an arm or leg. During ILI, high doses of chemotherapy medications are injected into an artery or vein within the affected limb while the blood is temporarily stopped with a tourniquet. It is believed that infusion may kill more tumor cells and cause less damage to healthy tissue.

How Chemotherapy is Administered
Chemotherapy is usually administered on an outpatient basis and is typically given in cycles. This means that treatment is given for a specified time and a rest period follows. Another cycle of treatment followed by rest is given as needed.

Chemotherapy may be combined with another form of treatment called immunotherapy, which uses the patient’s own immune system to fight the cancer. When chemotherapy is combined with immunotherapy, side effects tend to be less severe. Radiation therapy may be combined with chemotherapy to ease the symptoms of advanced metastatic melanoma.

Side Effects
Chemotherapy damages normal cells as well as cancer cells, and side effects, such as nausea, vomiting, mouth sores, fatigue, and hair loss are well known. What surprises many patients and family members is that side effects, such as nausea and hair loss do not always occur. Side effects depend on the medication used. Be sure to discuss side effects with your physician so you know what you can expect. It is important to know that there are many ways to minimize side effects. In fact, the coping techniques are so numerous that they are beyond the scope of this article. If chemotherapy becomes a treatment option, be sure to discuss ways to manage side effects with your physician.

Systemic Chemotherapy Medications Used to Treat Melanoma
(DTIC) is the only anti-cancer medication that has been approved by the U.S. Food and Drug Administration (FDA) for treating metastatic melanoma. Studies indicate that it has been effective in reducing tumors in approximately 15% of patients, and remission is typically maintained for 3 to 6 months. Dacarbazine is given intravenously (by IV) for 1 to 10 days. The dosing schedule depends on the patient’s condition and ability to tolerate side effects that may include nausea, vomiting, pain at the injection site, and fatigue.

Temozolamide, another anti-cancer medication, belongs to the same class of medications as DTIC. Both are alkylating agents, which means the medications work by binding together the DNA in cancer cells. This action prevents the cells from growing, and the cells die. Temozolamide is given in pill form rather than intravenously. Tumor reduction is similar to DTIC.

Other anti-cancer medications that have been tested as a single agent (one anti-cancer medication is selected for its activity in treating the patient’s type and stage of metastatic disease) to treat metastatic melanoma include vincristine, vinblastine, cisplatin, and carboplatin. None, to date, has shown a better response rate than DTIC.

While DTIC and temozolamide have been effective in reducing tumors in approximately 15% of patients and maintaining remission for 3 to 6 months, no single medication when used alone has been shown to produce long-term (5-year) survival in a significant number of patients with metastatic melanoma.

Anti-cancer medications are sometimes given via combined-agent chemotherapy, the combining of two or more chemotherapeutic agents. Combined-agent chemotherapy is used to either 1) enhance the effectiveness of chemotherapy or 2) avoid the cancer cells from growing resistant to a single agent. DTIC is usually one of the anti-cancer medications used in the combination.

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