Melanomas are for the most part radioresistant. However, radiation therapy is sometimes used as palliative therapy for stage III and IV melanoma patients to relieve symptoms and improve the quality of life. Although radiation cannot cure advanced melanoma, it often shrinks tumors that cause discomfort. Radiation is the primary treatment for patients with CNS metastases. Postoperative radiation therapy also may help decrease residual neurological symptoms such as partial paralysis, headaches, and seizures in patients with CNS metastases.
Radiation therapy may be offered to patients who cannot be considered for surgery. It is rarely used to treat primary melanoma, except in cases where patients are poor candidates for surgery or refuse surgical treatment.
Radiation therapy has also been applied to the regional lymph node basin to try to prevent recurrence of the tumor after surgery.
Even if the surgical margins are found to be clear, some patients are offered chemotherapy as adjuvant therapy to kill any cancer cells that may be left. Chemotherapy is an adjuvant treatment often used for Stage IV disease and recurrent melanomas, and for lower stages if surgery is contraindicated.
However, chemotherapy as adjuvant treatment for patients with advanced-stage melanoma (stage IV) has been found to have only partial success. Chemotherapy drugs for the treatment of melanoma may be administered singly or in combination, or in conjunction with immunotherapy.
The most effective chemotherapy regimen to-date is the single-agent dacarbazine (DTIC), which is only successful in 10-15% of cases. Two combination chemotherapy regimens commonly used in the treatment of patients with advanced-stage melanoma are the cisplatin, vinblastine, and DTIC (CVD) regimen and the Dartmouth regimen, which is a combination of cisplatin, DTIC, carmustine, and tamoxifen.
When melanoma occurs in the extremities, chemotherapy agents may be delivered via hyperthermic isolated limb perfusion. With this technique, the blood flow to and from the limb is stopped using a tourniquet, and a warmed solution of chemotherapy drug is administered directly into the blood of the limb, allowing higher doses of drugs to be dispensed than with systemic treatment.
Hormonal therapy slows or actually stops the growth of certain types of cancer by increasing or eliminating hormonal levels or blocking hormonal action in the body. Hormonal treatment of melanoma has been investigated since the early 1970s. The use of tamoxifen (a hormonal therapy drug used effectively to treat breast cancer) to treat melanoma is controversial. As a single agent, tamoxifen has been found to have a success rate of only 6%. However, recent findings have shown the combination of dacarbazine and tamoxifen for metastatic melanoma to be effective in approximately 30% of cases, a benefit observed primarily among women.
Similarly, a chemohormonal regimen consisting of tamoxifen, dacarbazine, carmustine, and cisplatin, called the Dartmouth regimen, has been shown to produce a high response rate in patients with metastatic disease.
Another hormonal therapy being evaluated is daily oral melatonin. Melatonin is a melanocyte-suppressive hormone that has been found to suppress tumor growth and stimulate the immune system in animal models.
Biological Response Modifiers
For treatment of melanoma, biological therapy is often utilized as adjuvant therapy following surgery to remove the melanoma, and is also used to treat advanced and recurrent melanoma.
Adjuvant interferon (IFN) alfa-2b and various experimental melanoma vaccines show potential in individuals with high-risk melanoma and those with regional nodal disease.
Biologic response modifiers such as GM-CSF, interleukins (IL-2, IL-12), and IFN gamma are often integrated into vaccine strategies. Although there is currently no clinical trial data that demonstrates a survival benefit for vaccine-treated melanoma patients, multiple studies are in progress.
Anti-angiogenesis therapy is a type of biological therapy that uses angiogenesis inhibitors to prevent or alter the growth of new blood vessels that feed malignant tumors, including melanomas.
Gene therapy consists of introducing new genetic material to damaged genes or cancer cells. The purpose of gene therapy is to exchange damaged cells with healthy ones, and to enhance the sensitivity of the melanoma cells to the immune system, immunotherapy, and chemotherapy.