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Melanoma Cancer Chemotherapy

A Patient's Guide to Chemotherapy Drugs for the Treatment of Metastatic Melanoma

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Updated May 21, 2009

Melanoma Cancer Chemotherapy

There are many types of chemotherapy used to treat metastatic melanoma

Photo: Mark Harmel / Getty Images
Cancer chemotherapy is a form of treatment that involves taking one or more of a type of drug that interferes with the DNA (genes) of fast-growing cells. They are usually given by IV infusion (slowly injected into your vein), but can be given orally (in pill form) or by direct infusion into a limb or the liver. Chemotherapy is often contrasted with targeted (biologic) therapy or immunotherapy, which attack specific parts of specific cells instead of all dividing cells.

Chemotherapy has long been a mainstay for treating metastatic melanoma (that is, melanoma that has spread beyond its site of origin). Unfortunately, there isn't a clear consensus among doctors about the most effective use of these drugs, which most likely reflects their low level of activity. Nevertheless, chemotherapy does help some people and so different types are available, including the following:

dacarbazine (DTIC-Dome) is currently the only FDA-approved chemotherapy drug for metastatic stage IV melanoma. While it is the best available treatment and the standard against which new melanoma drugs are evaluated, it produces a response in only about 15% of people and has no effect on overall survival.

temozolomide (Temodar, Temodal) is only FDA approved to treat brain cancer but it is also often used in patients with melanoma that has spread to the brain or nervous system. Temozolimide comes in convenient pill form, so some doctors prescribe it for patients who have difficulty with IV infusions or are unable to travel to a healthcare facility for the equally effective dacarbazine injection.

paclitaxel (Taxol) is an antimicrotubule agent that was originally isolated from the bark of the Pacific yew tree. Although it's still experimental in patients with melanoma, a 2006 study measured a small but significant response in 45% of patients when it was used in combination with another chemotherapy drug, carboplatin. Its serious side effects may include a decrease in the number of white blood cells and allergic reactions. A different version of paclitaxel called Abraxane, which has been shown to cause fewer allergic reactions, is now being tested in melanoma patients.

cisplatin (Paraplatin) targets fast-dividing cells, like cancer cells, and causes them to die. It is modestly active in melanoma and is often used in combination with other chemotherapy drugs; the CVD (cisplatin, vincristine and dacarbazine) regimen is an example of this. Serious side effects may include a decrease in the number of blood cells in your bone marrow, kidney impairment, and hearing loss.

carmustine (BCNU) is an "alkylating agent" that disrupts rapidly dividing cells. It is used to treat various cancers, including melanoma, that have spread to the brain. Carmustine can cause a decrease in the number of blood cells in your bone marrow as well as lung damage, even years after treatment.

fotemustine is another alkylating agent that is being tested in patients with metastatic melanoma, including those with brain tumors. A 2004 phase III trial showed that it was slightly superior to dacarabazine in terms of response rate and overall survival. However, the study also showed that fotemustine caused a much higher frequency of neutropenia (low number of white blood cells) and thrombocytopenia (low number of platelets in the blood) than dacarbazine. It has been found to have encouraging activity in patients with brain metastases and has been approved in Europe.

vindesine (Eldisine, Fildesin) belongs to the class of chemotherapy drugs called "vinca alkaloids," which were isolated from the Madagascar periwinkle plant. These drugs destroy dividing cells by disrupting their microtubules during cell division. While initially promising in the treatment of melanoma, a 2008 study showed that vindesine given after surgery did not significantly prolong disease-free or overall survival and had serious side effects, including a reduction of the number of white blood cells by the bone marrow, anemia (low numbers of red blood cells), hair loss, and numbness in the hands and feet (peripheral neuropathy).

vincristine (Oncovin, Vincasar) is another vinca alkaloid that inhibits cell division. It is used in various melanoma combination treatments, including the CVD (cisplatin, vincristine and dacarbazine) and BVLD (bleomycin, vincristine, lomustine and dacarbazine) regimens. A new version of vincristine -- called "vincristine sulfate liposome infusion" or VSLI -- is being tested in patients with melanoma and has shown promising activity with fewer side effects.

bleomycin (Blenoxane) is an antibiotic that is also a common component of chemotherapy regimens such as BVLD and BVT (bleomycin, vinorelbine, trofosfamide). It is being investigated as part of a new technique for treating melanoma that has metastasized to the skin called "electrochemotherapy," which uses electricity to force a chemotherapy drug directly into the tumor cells.

The bottom line is that, unfortunately, chemotherapy as an overall strategy is not very effective in treating melanoma. Only 15% to 20% of patients respond to chemotherapy, it typically only works for less than a year, and it has little to no effect on survival time -- not to mention the side effects. Hopefully, the new approaches to the treatment of metastatic melanoma being tested now -- such as targeted therapy, vaccines, and immunotherapy -- will prove to be more effective and less toxic.

Sources:

Avril MF, Aamdal S, Grob JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004 Mar 15;22(6):1118-25.

Eigentler TK, Radny P, Hauschild A, et al. Adjuvant treatment with vindesine in comparison to observation alone in patients with metastasized melanoma after complete metastasectomy: a randomized multicenter trial of the German Dermatologic Cooperative Oncology Group. Melanoma Res. 2008 Oct;18(5):353-8.

Rao RD, Holtan SG, Ingle JN, et al. Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma. Cancer. 2006;106:375-382.

"Chemotherapy." American Cancer Society. 28 April 2009.

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