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.
The following is FDA approved:
- DTIC (dacarbazine) Learn about DTIC by clicking here.
Experimental Approaches in Chemotherapy Include:
The most commonly used single-agent chemotherapies are:
- Temodar (temozolomide) 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 Temodar is as effective as DTIC 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.
- Taxol (Ppaclitaxel) 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.
- Cisplatin and Carboplatin belong to a a group of drugs known as platinating agents. These are typically used in combination chemotherapies rather than alone.
- BCNU (carmustine) 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 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 DTIC alone.
- CVD: a combination of Cisplatin, Vinblastine and DTIC. Studies have not shown CVD to be significantly more effective than DTIC alone. CVT (where DTIC is replaced by Temodar is occasionally used.)
- Dartmouth Regimen: a combination of Cisplatin, DTIC, Carmustine and Tamoxifen. In a phase II randomized study, it was shown that this regimen was not better than single agent DTIC.
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. 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
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.
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