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Kaposi’s Sarcoma

Overview

Kaposi’s sarcoma causes abnormalities to develop in the tissues below the skin surface anywhere on the body or in the mucous membranes of the mouth, nose, or anus. These skin abnormalities occur on the lower limbs in 90% of cases and appear as raised and discolored blotches or lumps that may be disfiguring but rarely cause discomfort or pain.

Kaposi’s sarcomas are usually not life threatening or disabling, but the condition may become life threatening when the cancer spreads to the lungs, liver, or gastrointestinal tract. Metastatic Kaposi’s sarcoma is associated with major symptoms, such as bleeding in the gastrointestinal tract or difficulty breathing due to lung metastases.

Kaposi’s sarcoma is caused by a type of herpes virus, called Kaposi’s sarcoma-associated herpes virus (KSHV or HHV-8). This disease was once considered very rare and affected primarily Mediterranean or eastern European men. In the last 20 years, however, most Kaposi’s sarcoma cases have developed in individuals with the human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). These groups have a weakend immune system, making them more vulnerable to the virus that causes this tumor. HIV-infected persons have a 450-fold increased risk of Kaposi’s sarcoma. When Kaposi’s occurs in AIDS patients, it progresses rapidly and responds poorly to treatment.

Other groups who suffer from suppressed immunity are also at a higher risk for developing Kaposi’s sarcoma. Recipients of solid organ transplants, including kidney, heart, and liver, have a 128-fold increased risk of developing the disease.1

The virus that causes Kaposi’s sarcoma is sexually transmitted, which accounts for the high rate of spread among homosexual men. Recent research indicates that the disease appears to occur in families, suggesting a genetic component to susceptibility.2 Since the majority of Kaposi’s sarcoma occurs in AIDS patients and transplant patients, the following treatment information will focus on these two groups.

About this Kaposi’s Treatment Information

The following is a general overview of treatment for Kaposi’s sarcoma. Treatment may consist of surgery, chemotherapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques has become an important approach for increasing a patient’s chance of cure and prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment.

Circumstances unique to each individual’s situation influence which treatment or treatments are utilized. The potential benefits of combination treatment, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

  • Kaposi’s Sarcoma in HIV-infected Individuals
    • Treatment for AIDS-related Kaposi’s sarcoma
    • Treatment of recurrent or refractory Kaposi’s sarcoma
    • Early chemotherapy for flare of Kaposi’s after initiation of HAART
  • Kaposi’s Sarcoma in Transplant Patients
  • Treatment of Classic Kaposi’s Sarcoma

Kaposi’s Sarcoma in HIV-infected Individuals

Researchers have observed that malignancy is becoming a major cause of death among HIV-infected individuals in industrialized nations. Historically, the most common cause of death for individuals with AIDS has been infection; however, deaths due to AIDs-related malignancy have increased to 28%. This has increased from 10% observed prior to the use of highly-active antiretroviral therapy (HAART).3 These findings indicate that HAART is prolonging survival but making patients more susceptible to developing cancer.

Treatment for AIDS-related Kaposi’s sarcoma: There are currently no curative treatment options for patients with AIDS-related Kaposi’s sarcoma. These patients are initially treated with combination chemotherapy. Doxil® (liposomal doxorubicin) may be the most active drug for the treatment of Kaposi’s sarcoma and has the advantage of causing less heart damage than standard doxorubicin.4 While chemotherapy is not curative, it does relieve symptoms in approximately half of patients.

The topical Panretin® gel (alitretinoin), comprised of a derivative of vitamin A as its active ingredient has been shown to be beneficial in one-third (35%) of patients treated with Panretin gel experienced a positive response to treatment compared to 18% who responded to a placebo.5 Panretin gel is FDA approved for the treatment of AIDS-related Kaposi’s sarcoma.

Treatment of recurrent or refractory Kaposi’s sarcoma: The chemotherapy drugs Taxol® (paclitaxel) and Taxotere® (docetaxel) appear to be active treatments for recurrent or refractory Kaposi’s sarcoma.

Taxol has been found to cause tumors to shrink significantly in the majority of patients with advanced Kaposi’s sarcoma who have not responded to previous systemic chemotherapy. Overall, more than half (56%) of patients treated with Taxol experience an anticancer response, and the responses last an average of almost nine months. The majority of patients who responded (70%) did so after six weeks of treatment and four cycles of therapy. However, complete anticancer responses were observed in only four of the 54 patients who responded. Patients who responded to treatment also experienced a significant improvement in quality of life. It has not been determined whether Taxol may extend survival.6

Taxotere has also been shown to produce partial anticancer responses in nearly half of patients with recurrent disease and produced stable disease in another one-third of patients. On average, patients survived more than two years without disease progression.7

Early chemotherapy for flare of Kaposi’s after initiation of HAART: Researchers have reported a worsening of Kaposi’s sarcoma with the initiation of HAART. A flare-up of Kaposi’s is associated with a fatal disorder of the immune system, called immune reconstitution inflammatory syndrome (IRIS), which may follow initiation of HAART. An IRIS-associated flare does not necessarily result in a poor prognosis. Even for those patients with a rapid and symptomatic onset, early systemic chemotherapy can effectively suppress an IRIS-associated flare. Close clinical supervision of patient initiating, changing, or resuming HAART may lead to earlier diagnosis of IRIS-associated flare, when it is most treatable.8

Kaposi’s Sarcoma in Transplant Patients

Patients who receive solid organ transplants are at increased risk of developing Kaposi’s sarcoma. However, this is not the same aggressive disease that is seen in patients infected with HIV. Kaposi’s sarcoma in transplant patients often remains localized to the skin, however it may become widespread and spread to other organs.

The usual management is to reduce the doses of immunosuppressive drugs once Kaposi’s sarcoma is diagnosed. This requires carefully balancing the risk of death from generalized Kaposi’s sarcoma and the risk of organ rejection and complications of renal failure that may occur if the immunosuppressive therapy is discontinued.

In a clinical trial involving 14 kidney transplant recipients who developed Kaposi’s sarcoma, all but one had their tumors completely disappear after their immunosuppressive drugs were discontinued. One patient required chemotherapy, and two had a deterioration of renal function.

Most patients receive cyclosporine for immunosuppression after a kidney transplant. Sirolimus (rapamycin) is an alternative to cyclosporine. Researchers from Spain first noted that Kaposi’s sarcoma regressed after substituting sirolimus for cyclosporine. They observed two patients who had complete regression of Kaposi’s sarcoma after discontinuing cyclosporine and starting sirolimus. A small clinical trial involving 15 renal transplant patients has confirmed this finding. Three months after changing to sirolimus, all patients had a complete disappearance of the Kaposi’s.9

Treatment of Classic Kaposi’s Sarcoma

Kaposi’s sarcoma that occurs in individuals who are not infected with HIV or are not transplant patients is a rare disease. It typically runs a benign course that may last 10 to 15 years or more with slow enlargement of the original skin abnormalities and the gradual development of additional ones.

Single tumors may be removed with surgery or laser therapy, or frozen off with cryotherapy. Advanced disease requires systemic chemotherapy. Two of the most commonly used drugs in the treatment of Kaposi’s sarcoma are pegylated liposomal doxorubicin (Doxil®) and interferon alfa-2a (IF-alfa). In one German study, monthly administration of Doxil was found to be superior to IF-alfa therapy.10

The combination of vinblastin and bleomycin appears to be an active initial chemotherapy treatment for advanced Kaposi’s sarcoma. More then three-quarters of patients have an immediate response to treatment and one in five patients experience a complete anticancer response. On average anticancer responses lasted four months and a maximum of five months.11

References


1 Serraino D, Angeletti C, Carrieri MP, et al. Kaposi’s sarcoma in transplant and HIV-infected patients: an epidemiologic study in Italy and France. Transplantation. 2005;80:1699-1704.

2 Guttman-Yassky E, Kra-Oz Z, Dubnov J, et al. Infection with Kaposi’s sarcoma-associated herpesvirus among families of patients with classic Kaposi’s sarcoma. Arch Dermatol. 2005 Nov;141(11):1429-34.

3 Bonnet F, Lewden C, May T, et al. Malignancy-Related Causes of Death in Human Immunodeficiency Virus-Infected Patients in the Era of Highly Active Antiretroviral Therapy. Cancer. 2004;101:317-324.

4 Theodoulou M and Hudis C, Cardiac Profiles of Liposomal Anthracyclines. Greater Cardiac Safety Versus Conventional Doxorubicin? Cancer. 2004;100:2052-1063.

5 Walmsley S, Northfelt DW, Melosky B, et al. Treatment of AIDS-related cutaneous Kaposi’s sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group.Journal of Acquired Immune Deficiency Syndrome. 1999;22(3):235-46.

6 Tulpule A, Groopman J, Saville MW, et al. Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi’s sarcoma. Cancer. 2002;95:147-154.

7 Lim ST, Tupule A, Espina BM, et al. Weekly docetaxel is safe and effective in the treatment of advanced-stage acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer. 2005;103:417-421.

8 Leidner RS, Aboulafia DM. Recrudescent Kaposi’s sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. AODS Patiet Care STDS. 2005;19:635-644.

9 Stallone G, Schena A, Infante, et al. Sirolimus for Kaposi’s sarcoma in renal transplant recipients. New England Journal of Medicine. 2005;352:1317-1323.

10 Kreuter A, Rasokat H, Klouche M, et al. Liposomal pegylated doxorubicin versus low-dose recombinant interferon Alfa-2a in the treatment of advanced classic Kaposi’s sarcoma; retrospective analysis of three German centers. Cancer Invest. 2005;23:653-659.

11 Brambilla L, Miedico A, Ferrucci S, et al. Combination of vinblastine and bleomycin as first line therapy in advanced classic Kaposi’s sarcoma. J Eur Acad Dermatol Venereol. 2006 Oct;20(9):1090-4.

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