- Review of melanoma treatment methods
- Immunotherapy for melanoma
- Targeted therapy for melanoma
- Chemotherapy for melanoma
- Radiotherapy for melanoma
- How is melanoma treated depending on the stage?
Melanoma treatment: methods and drugs
After a melanoma diagnostics and confirmation of diagnosis, it is necessary to choose an appropriate treatment. It can include surgery, irradiation, and medicamentous therapy.
Removal of neoplasm is a main way of melanoma treatment at the early stages. Excisional biopsy which supposes a complete removal of a suspicious mole, is not only a diagnostic procedure for the detection of malignant neoplasm, but therapeutic one - if a diagnosis is confirmed.
At the advanced stages of disease, only a surgical method is not enough. If oncological process affects the lymph nodes, or the removal of neoplasm is impossible, medicamentous therapy of melanoma is assigned.
How is melanoma treatment with therapeutic drugs assigned?
Today, three schemes of medication taking are applied. Doctors use them depending on the disease stage:
- neoadjuvant therapy - before surgical removal of the formation in order to reduce the size of the tumor and the defect after its surgical removal;
- basic therapy - as the only possible way to get rid of melanoma;
- adjuvant therapy - after the main treatment (surgical removal) of neoplasm in order to get rid of malignant cells that could remain in the body.
Medicamentous treatment method consists of immunotherapy, chemotherapy, and radiotherapy. They can be applied at the different disease stages.
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Immunotherapy for melanoma
Nowadays, different treatment options are applied for melanoma. One of the most promising of these is immunotherapy.
Immunotherapy (or biological therapy) is a usage of biological medications for treatment at the advanced disease stages. They are human immunity proteins created in the laboratory.
Immune medications are effective in fighting melanoma, but have side effects, so their use should be strictly controlled by a doctor!
Immunotherapy drugs for melanoma
Immunotherapeutic drugs for the systemic treatment of melanoma differ in the main active substance. -alpha (Intron-A) and interleukin-2 (Proleukin) for therapeutic purposes are administered at high therapeutic doses. They stimulate the body's immune cells to identify and eliminate malignant tumor cells.
-alpha is often used as a drug for adjuvant therapy to reduce malignant neoplasm and prevent its spread throughout the body. It significantly reduces the risk of recurrence and further metastasis. Interleukin-2 is one of the basic drugs used in the treatment of melanoma. It is administered in case of risk of significant lymph node involvement with tumor metastases.
Peginterferon-alfa-2b, or pegylated interferon-alfa-2b is also an effective substance for the treatment of melanoma, which has a persistent relapse-free effect.
-alfa, interleukin-2 are administered into the body with intravenous injection. In some cases, interferon-alfa and IL-2 can be administered subcutaneously into the tissue affected by melanoma.
-alfa, peginterferon-alfa-2b and interleukin are substances that have systemic impact on the entire body. A new generation of drugs based on monoclonal antibodies causes the destruction of malignant cells without harm to healthy organs.
One of the newest drugs is ipilimumab (Yervoy).
Ipilimumab is a substance which belongs to the monoclonal antibodies and activates the immune response of a person to malignant cells in the body.
Pembrolizumab () is the newest medication that is applied if treatment with previous medications appeared as ineffective. increases a reaction of the organism immune system against tumor cells without causing significant affection of the healthy tissues.
Nivolumab like Pembrolizumab () is a new and promising drug for melanoma treatment.
Nivolumab is effective for reduction of sizes of inoperative tumors and treatment of patients in the case of ineffectiveness of other drugs.
TIL-immunotherapy
TIL-immunotherapy is a subdivision of immunotherapy which is used for treatment of patients with melanoma at the advanced stages.
TIL (Tumor-infiltrating lymphocytes) are lymphocytes which penetrate in the malignant neoplasm for its destruction. TIL are 75 times more active the usual lymphocytes in the blood.
A surgeon removes a malignant neoplasm surgically. Then doctors detect TIL-cell from the material. The most active among them are multiplied and administered back into the organism. Such therapeutic method does not cause rejection because TIL are extracted from a patient’s body. For the accelerated impact, TIL-immunotherapy is combined with the immune drugs, for instance, interleukin-1.
Targeted therapy for melanoma
Targeted therapy is a new method for treatment of malignant neoplasms. It is developed for a specific influence in the pathological cells. Targeted drugs influence on the tumor cell receptors causing their death. MEdications of this group can be effective only in the case if there is BRAF mutation in the malignant cells. They are the target for the medications.
BRAF-mutation is an abnormal change of the gene, which is detected in 40-70% of patients with a melanoma diagnosis.
BRAF is a gene which encodes a protein responsible for one of signal ways in the cell. Typically, it is inactive, but in the case of mutation, activates overgrowth of the cells. The result is a rapid overgrowth of malignant neoplasm.
Medications for targeted therapy at the advanced stages and relapse of melanoma
Actual substance | Brand name | Mutation of a gene |
|---|---|---|
Dabrafenib | Tafinlar 2013 | BRAF |
Trametinib | Mekinist 2013 | BRAF |
Vemurafenib | Zelboraf 2011 | BRAF |
Cobimetinib | Cotellic 2015 | BRAF |
Imatinib | Gleevec 2015 | c-KIT |
Dabrafenib (Tafinlar) is one of the targeted antitumoral substances, which is used for the treatment of inoperable melanoma in patients with BRAF V600E and V600K mutations. Specialists do not combine a dabrafenib-based drug with different treatment options (incl., chemotherapy or radiotherapy). But it is possible to combine a dabrafenib with other targeted drug - a trametinib-based Mekinist.
Trametinib (Mekinist) is a substance which is also effective for melanoma. Doctors use it for patients with BRAF V600E and V600K mutations.
Vemurafenib (Zelboraf) is a highly active substance which is applied for treatment of patients with BRAF V600E mutation. Vemurafenib increases a survival rate of patients with melanoma and in combination with cobimetinib (Cotellic, a drug reduces risk of the further progressiveness of disease by twice.
Imatinib (Gleevec) is one of the best-targeted drugs for melanoma treatment in patients with the c-KIT mutation. Among mutations, connected with a skin tumor development, a quantity of cases with c-KIT is approximately 5%, but the effectiveness of this drug is very high in these cases.
Targeted medications are available in the form of tablets for swallowing, which is a very convenient option for the patient. It does not require long hospitalization.
Chemotherapy for melanoma
Chemotherapeutic drugs have a systemic effect when the blood flow is carried throughout the body. Therefore, it negatively impacts healthy tissues.
The effectiveness of melanoma treatment with "pure" chemotherapy is low.
That is why today chemotherapy is prescribed only in combination with immunotherapeutic and targeted drugs for the effective treatment of melanoma with a high risk of metastases and relapses. This approach is called biochemotherapy. It allows reducing the dose of chemotherapy and preventing severe side effects.
Specialists choose the drugs and chemotherapy regimens individually for each patient. Cycles include days of medication and rest days. Most often chemotherapy drugs are administered intravenously.
Local chemotherapy
If melanoma affects arm or foot tissues, doctors apply a method of isolated limb perfusion. It is one of the local chemotherapy types. Its aim is a “delivery” of chemo drug to the affected organ with minimal influence on the whole organism.
With a catheter inserted into a vein, a chemical drug gets to the blood vessels of the affected limb, and it "disconnects" from the general circulation. This approach allows applying chemotherapy locally and avoiding serious side effects.
Topical therapy for melanoma
In the case, if removal of relapsed melanoma is impossible, doctors prescribe topical therapy. A drug is applied locally on the external tissues. Active substances in the form of an ointment or cream are placed on the outer layer of the affected skin. If melanoma is located on the face, topical therapy helps to avoid surgery, however only in the case of small tumor size.
Radiotherapy for melanoma
Radiotherapy is a method of powerful irradiation for the destruction of malignant cells. Its aim is the maximum impact of the affected tissues with minimal influence on the health.
Radiotherapy method almost only is not used for the treatment of primary melanoma.
Radiotherapy is performed as palliative therapy to reduce pain with recurrent melanoma and metastatic lesions of brain tissue and bones.
For the removal of metastases in the brain and other organs, doctors prescribe radiosurgical method.
It is a safer alternative to surgical intervention.
Such methods are used for the treatment of melanoma metastases:
How to treat melanoma depending on stage?
Treatment of melanoma in situ
At stage 0, doctors remove the neoplasm surgically. If a tumor is located on the face, such an approach can be inapplicable because of possible cosmetic problems. In this case, doctors recommend conducting a topical therapy: a patient uses special cream contained imiquimod - Zyclara, Aldara.
Only a doctor can prescribe treatment for melanoma!
Therapy for melanoma stage 1
At the 1st stage, if the size of neoplasm is less than 1 mm, surgical intervention involves excision with capture of the healthy skin of 1 cm. If a tumor size is up to 2 mm, no more than 2 cm of healthy skin is removed from all sides of the neoplasm.
At stages 0-1 of melanoma, surgical removal of a tumor is the main and the only method of treatment. In such cases, a person is completely cured, and there is practically no risk of melanoma recurrence. Adjuvant therapy after removal of a tumor stage 0-1 is not assigned.
In some cases, during at stage 1 of melanoma, a biopsy of the sentinel lymph node may be required to prevent the spread of the process. Patients with melanoma stage 0-1 after the treatment should regularly visit a doctor at least once a year for 5 years. It is also necessary to check on a regular basis the regional lymph nodes and, if they are enlarged, to consult a doctor immediately.
Treatment of melanoma stage 2
At stage 2, the primary method of treatment is a wide excision of a tumor within the healthy tissue. At this stage of the disease, a specialist performs a biopsy of the sentinel lymph node to detect or exclude the process of metastatic spread. Some patients with melanoma stage 2 are assigned interferon-alfa as adjuvant therapy.
After treatment of melanoma stage 2, a patient needs to visit a doctor 2-3 times a year for 2 years, then 1-2 times a year for 3 years. It is also recommended to conduct CT or PET-CT of the whole body at least 1 time per year. It detects possible metastases. It is necessary to conduct a regular self-examination of the affected area after surgical removal, as well as to check regional lymph nodes.
Treatment of melanoma stage 3
At stage 3, surgeons perform lymph nodes dissection - removal of the affected lymph nodes. They remove all the foci of tumor formations. In case of massive tissue affection, radiation therapy, chemotherapy or combined treatment are prescribed. If the tissues of the hands or feet are involved, isolated perfusion of the limb is performed. It is characterized by local influence and does not affect internal organs.
If surgical removal of the tumor is impossible, doctors use local or systemic drug therapy. Also, at stage 3 of melanoma, together with extensive excision of the tumor, regional lymph nodes are removed, too. As an adjuvant treatment, immunotherapeutic drugs are used.
Some patients after excision of regional lymph nodes can be prescribed radiotherapy. After the treatment of melanoma at the 3rd stage, it is necessary to visit a doctor 2-3 times a year for 2 years, then 1-2 times a year for 3 years. It is recommended to conduct at least 1 time per year CT or PET-CT of the whole body and MRI of the brain for early detection of possible metastases.
It is worth visiting a dermatologist for examination annually.
Treatment of melanoma stage 4
If the metastases in the internal organs are limited, it is possible to remove them surgically.
If surgical removal of metastases is not possible, systemic drug therapy is prescribed.
Treatment of melanoma stage 4 is performed using immunological drugs, targeted therapy, and biochemotherapy. In 2015, the treatment protocols for metastatic melanoma included promising drugs - and Opdivo. The use of immunological drugs in combination has made it possible to achieve significant results in the continuation of the life of patients with metastatic melanoma.
Technologies for the treatment of malignant skin neoplasms are constantly developing: already known methods (for example, chemotherapy) are being improved, new drugs and methods are being invented.
Since 2011, new drugs appeared that made it possible to treat even advanced melanoma.