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Chemotherapy

Chemotherapy is treatment with medicines that attack rapidly dividing cells through various mechanisms. Anticancer drugs are injected into a vein or given by mouth and they travel through the bloodstream after absorption or injection.

 

Chemotherapy has not been as effective for melanoma as for some other types of cancer, but may relieve symptoms in some patients with advanced melanoma that cannot be surgically removed (advanced Stage III or IV). It has been investigated as an adjuvant therapy (therapy after complete surgical removal of melanoma) to kill cancer cells that may remain after melanoma surgery, but it has yet to show any benefit in this group of patients. Clinical trials are being conducted to find more effective chemotherapy medications.

 


Single Agent Chemotherapy

Combination Chemotherapy

Isolated Limb Perfusion (ILP)

Side Effects of Chemotherapy

 

Single-Agent Chemotherapy

The most commonly used single-agent chemotherapies are listed below.

 

 

  • Temozolomide (brand name Temodar) is an oral drug approved for the treatment of certain types of brain cancer. It is used to treat advanced, metastatic melanoma. Clinical trials have shown that temozolomide is as effective as dacarbazine and, for patients who would rather take pills for treatment, it is easier to administer. (1) It also penetrates the blood brain barrier, which makes it an option for patients with brain metastases.

 

  • Paclitaxel (brand name Taxol) is a chemotherapy that interferes with cell division and has modest activity in metastatic melanoma. It is administered as an intravenous injection and can be given by itself or in combination with other agents, typically carboplatin.

 

  • Nab-Paclitaxel (brand name Abraxane) is a nanoparticle albumin-bound form of paclitaxel that was tested in a phase 3 trial versus dacarbazine. It showed significant improvement in progression free survival but does not extend overall survival.

 

  • Cisplatin and carboplatin below to a a group of drugs known as platinating agents. These are typically used in combination chemotherapies rather than alone.

 

  • Carmustine (also known as BCNU) and Fotemustine two drugs belonging to a group of drugs known as nitrosoureas.

 

Other Chemotherapy Agents: (less commonly used) include Vindesine, Vincristine, (alkaloid family), and Bleomycin (antibiotic family).

 

Combination Chemotherapy

Combination chemotherapy, the use of multiple chemotherapy drugs, at the same time, has not been proven to be superior to treatment with single agents but may have a role under certain circumstances. Combination chemotherapies are listed below.

 

  • Carboplatin/Paclitaxel is a combination of carboplatin and paclitaxel. It has shown activity in several clinical trials, but it has never been compared to dacarbazine alone.
  • CVD: a combination of cisplatin, vinblastine and dacarbazine. Studies have not shown CVD to be significantly more effective than dacarbazine alone. CVT (where dacarbazine is replaced by temozolomide) is occasionally used.
  • Dartmouth Regimen: a combination of cisplatin, dacarbazine, carmustine and tamoxifen. In a phase II randomized study, it was shown that this regimen was not better than single agent dacarbazine.

 

For more on clinical trials click here.

Isolated Limb Perfusion (ILP)

ILP is a method of administering chemotherapy at very high doses for Stage III or recurrent melanomas that are confined to a single arm or leg (limb). The procedure involves blood vessel surgery, in which the circulation of the involved limb is temporarily isolated from the rest of the body. High doses of the chemotherapy agent, melphalan, are injected into the artery supplying the limb. The blood and melphalan are then recirculated through a heart-lung machine and heated for a period of time, usually about an hour. The heating process, known as hyperthermia, enhances the drug's potency. The treated blood is then returned to the affected limb, so most of the drug reaches the tumor directly. Since other parts of the body are not exposed to treatment, side effects to the system are minimized.

 

ILP is useful in relieving symptoms of inoperable disease but has not been shown to prolong survival. There have been attempts at enhancing the effect of melphalan through the addition of tumor necrosis factor (TNF alpha) or interferon gamma, but recent studies showed no advantage of using the combination over melphalan alone. (2-3)

 

Isolated limb infusion (ILI) is a therapy similar to ILP but does not require surgery on the blood vessels. Instead, blood flow to the limb is stopped temporarily with a tourniquet while high doses of chemotherapy drugs are injected into the artery. This method appears to be as efficacious as ILP. (4)

 

Side Effects of Chemotherapy

The goal of chemotherapy drugs is to kill cancer cells. However, since chemotherapy targets cells that divide and grow rapidly, it also affects rapidly growing normal cells such as the blood-producing cells of the bone marrow, the cells lining the gastrointestinal tract and hair follicles. The destruction of normal cells produces a variety of side effects. The type and intensity of side effects depend on the type of drug, the amount administered and the length of treatment.

 

Normal Cells Destroyed / DamagedSide Effect
Lining of gastrointestinal tract Nausea and vomiting; diarrhea
Loss of appetite
Lining of mouth Mouth sores; changes in taste
Hair follicles Hair loss
Bone marrow Increased risk of infection and fever
(decreased numbers and function of white blood cells)
Bleeding or bruising from minor cuts or injuries
(decreased numbers and function of platelets)
Fatigue
(decreased number of red blood cells)


Most side effects are temporary and disappear once chemotherapy is stopped. However, some side effects can be longer lasting or permanent. A number of medications are available to be used with the chemotherapy to relieve severe side effects such as nausea and fatigue. Be sure to discuss side effects and their treatment with your cancer care team.

Kidney and Liver Damage

One of the main functions of the liver is to break down or eliminate harmful substances in the body, including medications, so that their by-products can be excreted into the bile or blood. Certain chemotherapy drugs or their by-products may be toxic to the liver, causing inflammation and other forms of liver damage, including liver failure.

 

The main function of the kidneys is to remove/filter waste products, including medications and the by-products of medications, from the blood and return the cleansed blood back into circulation. Each kidney is composed of thousands of tiny filtering units that retain substances the body needs and excrete wastes in the form of urine. Certain chemotherapy drugs may accumulate in the kidney in higher concentrations than the kidney can adequately filter, resulting in kidney damage or kidney failure.

 

Patients undergoing chemotherapy are carefully and continuously monitored for kidney and liver function. Chemotherapy dosages may need to be adjusted to prevent organ damage. In addition, a drug dosage that is well tolerated in a healthy kidney or liver may be toxic to a damaged organ. It is important that you inform your doctor of all medications, including over the counter medicines and supplements, that you use on a regular basis as this could effect your cancer treatment, as well as kidney or liver function.

 

Contact your doctor immediately if you experience any of the following serious side effects:

  • Infection and fever over 100.5° F (38.1° C)

  • Persistent bleeding

  • Difficulty breathing

  • Difficulty swallowing

  • Persistent nausea and vomiting, with the inability to take fluids or food

  • Decreased production of urine

  • Swelling of the legs or other areas of the body

  • Dizziness

 

References:
1. Middleton MR, Grob JJ, Aaronson N, et al. Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients with Advanced Metastatic Malignant Melanoma. J Clin Oncol. 2000;18:158-166.
2. Cornett WR, McCall LM, Petersen RP, et al. Randomized Multicenter Trial of  Hyperthermic Isolated Limb Perfusion with Melphalan Alone Compared With  Melphalan Plus Tumour Necrosis Factor: American College of Surgeons Oncology Group Trial Z0020. J Clin Oncol. 2006;24(25):4196-4201.
3. Lienard D, Eggermont AM, Koops HS, et al. Isolated Limb Perfusion With Tumour Necrosis Factor-Alpha and Melphalan With or Without Interferon-Gamma for the Treatment of In-Transit Melanoma Metastases: A Multicentre Randomized Phase II Study. Melanoma Res. 1999;9(5):491-502.
4. Lindner P, Doubrovsky A, Kam PC, Thompson JF. Prognostic  Factors After Isolated Limb Infusion With Cytotoxic Agents for Melanoma. Ann Surg Oncol.2002;9(2):127-136.