What is melanoma?

Melanoma is a well-studied condition and a major public health threat with 2,341 deaths recorded from 2017-2019 according to Cancer Research UK. However, unlike common skin melanomas, Mucosal melanoma (MM) is less understood and develops from cells called melanocytes found in the mucus membranes of the body, such as the lining of the mouth, nasal passages and the genital areas. Melanocytes are the specialised cells which make melanin, the pigment which gives our skin colour and protects against harmful UV rays. Melanocytes are also found in mucosal tissues, however in regions which are not commonly exposed to sunlight, therefore the exact mechanism of how these cells become cancerous is unknown.¹

Currently, the main treatments used including surgery and radiation have had minimal success in improving survival rates. Researchers are looking into whether adding chemotherapy to current treatment plans could help improve the prognosis of the disease.

In this article we will explore whether chemotherapy could lead to effective treatment of the disease, discussing the challenges and current studies to find a better treatment.² 

Understanding mucosal melanoma and its symptoms

1.3% of all melanomas are mucosal melanomas (MM). Mucosal melanomas (MM) is a rare form of skin cancer (melanoma) which occurs in the melanocytes of the mucosal lining in the body, which can lead to tumours forming in internal tissues.⁵ 

Skin melanomas are often quite easy to spot in skin manifestations such as moles changing shape, size or colour. However,  mucosal melanomas are often hidden away and within the tissues of the body therefore, they go unnoticed until it is too late. Making the diagnosis of MM very challenging and hard to achieve at an early stage. Therefore they are usually discovered within patients once they have already taken on an advanced form and have spread to lymph nodes and major organs. This makes treatment all the more challenging.⁵

MM is often a very aggressive form of cancer and typically has a very poor prognosis. The survival rate for MM is often pretty low ranging from around 10-20% over a five year period. Although typical therapies such as surgery and radiation treatment are not particularly effective at treating this disease there has been research into novel therapies which could improve patient outcomes such as adjuvant chemotherapy.⁵

Recently, scientists have been able to identify the genetic characteristics of MM and where it differs from common skin melanomas. It was found to have a lower frequency of mutations in the BRAF gene, mutations which are highly prevalent in skin melanoma. A higher occurrence of mutations was found in the KIT gene. This new information is being implemented into the ongoing clinical trial research into treatment strategies for the condition and could help lead us to breakthroughs.⁵ 

What is chemotherapy?

Chemotherapy, is a vital component of cancer treatments, but how does it actually work to fight cancer?

Chemotherapy is a course of powerful drugs which have the ability to stop the growth and division of cancerous cells in the body which create tumours. The aim of the treatment is to decrease the size of tumours and potentially slow down the cancer's progression. Although it is a very effective treatment it comes with many adverse effects due to destroying normal safe cells such as in the hair, bone marrow (where immune cells are formed) and digestive tract. It can cause hair loss, nausea and an increased susceptibility to infections.³

Chemotherapy drug types

There are many different types of chemotherapy drugs which combat cancer through varying mechanisms. 

Alkylating agents

Alkylating agents are one of the main groups and these include drugs such as cyclophosphamide and temozolomide, these have the ability to destroy the DNA of cancer cells which stops them from multiplying and spreading throughout the body. 

Anthracyclines

Anthracyclines, such as doxorubicin, which affect DNA in cancer cells by inserting themselves into the DNA strands of dangerous cells. Alongside that they have the ability to kill cancer cells through the generation of free radicals.³ Chemotherapy is often used alongside other treatments such as surgery to remove tumours and radiation therapy to treat cancer patients. 

Clinical research on use of chemotherapy to treat  mucosal melanoma 

A case study looked at the effects of chemotherapy treatment on an 82-year-old woman with advanced stage mucosal melanoma. The treatment was employed after radiation to try and decrease the spread of cancer and the drug trofosfamide was used due to its effectiveness and the likelihood that it would not cause severe adverse effects. Trofosfamide works by interfering with cancer cell DNA and stopping the multiplication of cancer cells. 

Although mucosal melanoma often doesn't respond well to chemotherapy treatment, in this case there was a partial response in the patient. Where it was observed that some of her tumours decreased in size or stopped growing. An outcome which shows great promise as often mucosal melanoma spreads very aggressively. As well as this the treatment upheld the patients quality of life as the side effects of the drug in oral form were minimal and the patient received the treatment at home alongside her family.⁴

A study investigating the effects of chemotherapy on mucosal melanoma of the head and neck found that patients who had received adjuvant chemotherapy, meaning the chemotherapy was used after primary treatments, had significantly lower rates of recurrence. Primary treatments of the disease include surgery which is often the main treatment for this rare form of cancer. Although with surgery complete removal of the cancer cells from deep tissue is extremely challenging therefore additional treatments are vital to stop the cancer from coming back.

A study which investigated whether adjuvant chemotherapy (chemotherapy administered following primary treatments) lowers the rates of recurrent mucosal melanoma. This type of chemotherapy can be administered after surgery to fully remove all the cancer cells inhabiting the deep tissue in the body, which typically are extremely challenging to remove. It was found that adjuvant chemotherapy was able to help target these dangerous cells and significantly reduced recurrent cases in a small trial. 

Alongside the promising results, adjuvant chemotherapy also has very minimal side effects which meant that the patients receiving this treatment still had a high quality of life as this treatment could also be administered from home allowing patients to be with their families. 

This study also looked into the molecular characteristics of mucosal melanoma tumours, particularly looking at the proteins p53 and MDM2. 

These proteins are crucial in the control of cell growth and conducting cell death when necessary. A main takeaway from the research was that the patterns of these proteins were different to many more common types of melanoma which may be the reason that mucosal melanoma does not typically react so well to chemotherapy. 

Future directions 

Although this study produced very positive findings, there were some limitations that should be considered such as the small sample size of patients which may decrease reliability. To confirm these results a larger and more diverse set of patients would be required.²

FAQs

What is the role of chemotherapy in treating mucosal melanoma?

Chemotherapy often plays a secondary role in treating melanoma. It is used cancer has become advanced and spread to multiple areas of the body and removal of cancerous cells is not possible via surgery. Chemotherapy drugs such as dacarbazine and temozolomide are employed in such cases to help kill dangerous cells. Although mucosal melanoma and skin melanomas don't respond to chemotherapy it can be a useful addition to a treatment plan in certain cases.

What are the common chemotherapy drugs used for mucosal melanoma?

The chemotherapy drugs commonly used for mucosal melanoma include dacarbazine, temozolomide, and platinum-based drugs like cisplatin and carboplatin. These drugs work by damaging the DNA of cancer cells which prevents them from dividing and growing. Sometimes, chemotherapy drugs are used in combination with each other or with other treatments like immunotherapy to enhance their effectiveness. The choice of chemotherapy regimen depends on factors such as the stage of the cancer, the patient's overall health, and specific genetic characteristics of the tumour.

What are the side effects of chemotherapy for mucosal melanoma?

Chemotherapy affects cancer cells and healthy cells that divide rapidly, such as those in the hair follicles, bone marrow and digestive tract. 

Common side effects of chemotherapy may include nausea, vomiting, hair loss, fatigue and increased susceptibility to infections. Patients should discuss potential side effects with their healthcare team to receive appropriate supportive care throughout their treatment.

Is chemotherapy the only treatment option for mucosal melanoma?

No, chemotherapy is not the only treatment option for mucosal melanoma. Depending on the stage and location of the cancer, treatment may include surgery to remove the tumour, radiation therapy to target cancer cells with high-energy rays, immunotherapy to boost the body's immune response against cancer cells or targeted therapy to attack specific genetic mutations driving the cancer growth. A combination of treatments is used to achieve the best possible outcome for the patient. The choice of treatment plan is personalised based on individual factors and the specific characteristics of the cancer.

Summary

In conclusion, chemotherapy used in adjuvant to other treatments shows promise in the treatment of mucosal melanoma. Although it has only mainly been studied in small patient cohorts the efficacy of the treatment has been shown and the quality of life preserved with the treatment makes it an encouraging option for patients and their families. In future, larger clinical trials will be required to appropriately determine the effectiveness of chemotherapy treatment in the treatment of mucosal melanoma.