Introduction

Kaposi’s Sarcoma (KS) is a type of cancer which develops from the cells lining lymphatic or blood vessels. It is typically presented as tumours on the skin or mucosal membrane - the tissue that lines the body’s cavities and organs. It can also specifically affect internal organs, such as the gastrointestinal tract, lungs, or liver. 

KS has a strong association with human herpesvirus-8 (HHV-8) and primarily occurs in immunocompromised individuals, like those who have had an organ transplant and are on immunosuppressive therapy, or those with AIDS or HIV. 

Chemotherapy is a type of cancer treatment which uses drugs to kill or stop the cancer cells from progressing. While milder cases can be managed by antiretroviral therapy for individuals with HIV-related KS or radiotherapy for local treatment, chemotherapy is essential for aggressive KS.¹

This article reviews the effectiveness of different chemotherapy drugs for KS, how they work and their clinical outcomes. It will aim to discuss how treatments are adapted based on disease stage and immune status, and how these therapies are advancing in cancer treatment.

Understanding sarcomas and how Kaposi's sarcomas differ

Sarcomas are mesenchymal cancers, meaning they develop from connective tissues such as bone, muscle or fat, caused by genetic mutations. KS is a distinct vascular sarcoma caused by HHV-8 infections in immunocompromised patients. Unlike typical sarcomas, which can be characterised as solid tumours, KS are vascular and present as multiple skin or organ lesions. They spread more like an infection because it's linked to a virus (HHV-8), not just uncontrolled cancer growth like other tumours. So managing them requires a combination of chemotherapy and immune restoration.^2,3

Different variations of Kaposi's sarcoma

KS can be classified into four types, each one associated with different risk factors and populations.² 

Classic KS 

This typically occurs in older men of Eastern European or Mediterranean descent. Tumours of this type are less aggressive and can be managed with localised treatment like radiotherapy or surgical removal. 

Endemic KS

This affects the sub-Saharan African population and can affect individuals who aren't immunocompromised. Endemic KS presents as more aggressive, with tumours, and affects both the skin and internal organs.

Epidemic KS

This type is associated with AIDS and HIV and is common among individuals with weakened immune systems due to the virus. Tumours appear fast and can spread easily, affecting internal organs. Antiretroviral therapy can help manage HIV, but chemotherapy is required for epidemic KS. 

Immunosuppression-associated KS

This develops in patients receiving immunosuppressive therapy after an organ transplant or for autoimmune diseases. The risk of gaining KS rises due to the weakened immune system, allowing HHV-8 to become active and cause KS. 

When is chemotherapy used? 

Chemotherapy is used when KS becomes widespread, threatening organ failure. There are a couple of indications for when chemotherapy is used, including advanced cutaneous KS with multiple painful lesions which rapidly progress. Another example is visceral involvement, meaning the disease has spread to the internal organs, like the lungs, causing respiratory issues, or the lymphatic system, causing lymphoedema. Additionally, HIV associated KS continues to spread within the body, regardless of undergoing antiretroviral therapy; therefore, combining that with chemotherapy can help to reduce the mortality rate. Lastly, it can be used for post-transplant KS in organ recipients. 

It is important to note that not all KS cases will need chemotherapy, as early cases can be treated using local treatments.⁴

Types of chemotherapy for Kaposi’s sarcoma

First-line therapies

KS treatment relies primarily on systemic chemotherapy for advanced cases. Liposomal anthracyclines, particularly liposomal doxorubicin and daunorubicin, are used as first-line therapy. These drugs demonstrate high efficacy and safety due to the liposome formulation, which is used for targeted drug delivery, ensuring the drug only reaches areas of KS and not healthy cells. This reduces cytotoxicity, meaning healthy cells will remain alive rather than the drug attacking all healthy and unhealthy cells in the body. These are administered every 2-3 weeks by IV and can be synergistic when combined with antiretroviral therapy in HIV related KS and have a response rate of 60-70%.

Paclitaxel

For cases with advanced pulmonary involvement, paclitaxel is an effective option. Paclitaxel is a derivative of taxanes, which work by interfering with microtubules in cell division, stopping cell division, which is how cancerous cells continue to progress. Paclitaxel dosing is given weekly and has a response rate of 50-70% as it stabilises the microtubules, thus stopping them from further division and reducing the cancerous growth.⁸ 

Older regimens for chemotherapy, like doxorubicin-bleomycin-vincristine and single-agent vinca alkaloids, which work the same way as taxanes, are, however, more toxic to the body.^5,6

Combination therapies

Clinical management heavily implies how important it is to combine chemotherapy while also prioritising immune system restoration. In HIV-positive patients, this includes optimising antiretroviral therapy, while in organ transplant recipients, it may involve adjusting immunosuppressive treatment. The treatment length and type are individualised per patient based on therapeutic response and tolerability to the therapy. 

How is chemotherapy evolving?

Currently, research has been moving towards more targeted drug delivery and novel formulations like nanomedicine, micelles and liposomes, all of which create this barrier around the drug, which ensures that healthy cells in the body are not affected by chemotherapy, allowing for the sarcomas alone to be targeted by the drug. 

Before this, chemotherapy drugs were highly toxic and would cause severe damage and side effects to the body, such as heart damage, hair loss and myelosuppression.

Since the approval of liposomal doxorubicin in 1995, which offered fewer side effects than the traditional formulation, like reducing the hair loss and lower toxicity to cardio function, it also improved tumour targeting, leading to higher efficacy and response rates.⁷

FAQs

What is Kaposi's Sarcoma?

Kaposi sarcoma is a cancer derived from human herpesvirus 8 (HHV-8), which affects the blood and lymphatic vessels, occurring primarily in immunocompromised individuals. The list below indicates individuals who are more susceptible to KS:

• HIV/AIDS patients
• Immunosuppressed individuals, like those who have had an organ transplant
• People from sub-Saharan Africa
• Elderly men of Eastern European or Mediterranean descent

When is chemotherapy needed for KS?

Chemotherapy is used in four circumstances:

1. Rapid progression of KS, which is widespread or causes pain
2. Involvement of organs such as the lungs, liver, or intestines 
3. Post-transplant KS does not respond to reduced immunosuppression
4. HIV related KS, which doesn't respond positively to antiretroviral therapy alone

What are the common chemotherapy drugs used for KS?

First-line treatment is liposomal doxorubicin and daunorubicin, and second-line treatment is paclitaxel. Older therapies include doxorubicin-bleomycin-vincristine and vinblastine. 

How effective is chemotherapy?

Liposomal anthracycline formulations have a 60-80% success rate in practice, whereas paclitaxel has a slightly lower success rate of 50-70%. The effectiveness of these drugs is dependent on the disease stage and the immunity of the individual. 

How can you manage the side effects of KS during chemotherapy?

Maintain a healthy, well-balanced diet, partake in light exercise and rest to ease symptoms of fatigue. 

If you’re feeling nauseous, anti-nausea medication can be taken under the guidance of your GP. 

You can experience numbness or tingling in the hands or feet, which is more common with paclitaxel. Avoid extreme temperatures, and if it becomes extreme consult your GP on taking supplements, like vitamin B or medication.

Summary 

Kaposi’s sarcoma is an HHV-8 related vascular cancer that primarily affects immunocompromised individuals, including HIV/AIDS patients and transplant recipients. While localised KS can be treated with radiotherapy or surgery, chemotherapy is essential for more aggressive cases that are widespread. The most effective treatment with fewer side effects are liposomal anthracyclines like doxorubicin or daunorubicin, which offer targeted drug delivery and higher efficacy with reduced toxicity. Paclitaxel is used as a second-line treatment for more severe cases. 

Treatment strategies must be individualised and combined with immune restoration, optimising antiretroviral therapy for HIV patients or reducing immunosuppression in transplant recipients. The introduction of liposomal formulations increased the effectiveness and reduced the toxic effects the drugs cause to the body. 

The integration of both chemotherapy with immune system restoration has helped with many KS cases and allowed many patients to have a better quality of life and reduced mortality rates.