General Information About Kaposi Sarcoma

Epidemiology

KS was first described in 1872 by the Hungarian dermatologist, Moritz Kaposi. From that time until the current human immunodeficiency virus (HIV) disease epidemic identified with the Acquired Immunodeficiency Syndrome (AIDS), KS remained a rare tumor. While most of the cases seen in Europe and North America have occurred in elderly men of Italian or Eastern European Jewish ancestry, the neoplasm also occurs in several other distinct populations: young black African adult males, prepubescent children, renal allograft recipients, and other patients receiving immunosuppressive therapy. The disseminated, fulminant form of KS associated with HIV disease is referred to as epidemic KS to distinguish it from the classic, African, and transplant-related varieties of the neoplasm. In addition, KS has been identified in homosexual men apart from the HIV disease epidemic.[1 ]

Histopathology

Although the histopathology of the different types of the Kaposi tumor is essentially identical in all of these groups, the clinical manifestations and course of the disease differ dramatically.[2 ] A key piece to the puzzle of KS pathogenesis was the 1994 discovery of a gamma herpes virus, human herpes virus type 8 (HHV-8), also known as Kaposi sarcoma herpes virus.[3 ] HHV-8 was identified in KS tissue biopsies from virtually all patients with classic, African, transplant-related, and AIDS-associated KS but was absent from noninvolved tissue.[4 ,5 ,6 ,7 ]

Classic Kaposi Sarcoma

Considered a rare disease, classic KS occurs more often in males, with a ratio of approximately 10 to 15 males to 1 female. In North Americans and Europeans, the usual age at onset is between 50 and 70 years. Classic KS tumors usually present with one or more asymptomatic red, purple, or brown patches, plaques, or nodular skin lesions. The disease is often limited to single or multiple lesions usually localized to one or both lower extremities, especially involving the ankles and soles.

Classic KS most commonly runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesions. Venous stasis and lymphedema of the involved lower extremity are frequent complications. In long-standing cases, systemic lesions can develop along the gastrointestinal tract, in lymph nodes, and in other organs. The visceral lesions are generally asymptomatic and are most often discovered only at autopsy, though clinically, gastrointestinal bleeding can occur. As many as 33% of the patients with classic KS develop a second primary malignancy, which is most often non-Hodgkin lymphoma.[8 ,9 ,10 ]

African Kaposi Sarcoma

In the 1950s, KS was recognized as a relatively common neoplasm endemic in native populations in equatorial Africa and comprised approximately 9% of all cancers seen in Ugandan males. African KS is seen as either an indolent neoplasm identical to the classic disease seen in Europe and North America or as an aggressive disease with fungating and exophytic tumors that may invade the subcutaneous and surrounding tissue including the underlying bone. In Africa, both the indolent and locally more aggressive forms of KS occur with a male-to-female ratio comparable to that observed with the classic KS tumor seen in North America and Europe. In general, however, patients in Africa are significantly younger than their European counterparts. A lymphadenopathic form of KS is also seen in Africa, primarily in prepubescent children (male:female ratio, 3:1). In these cases, the generalized lymphadenopathy is frequently associated with visceral organ involvement. The prognosis is very poor with a 100% fatality rate within 3 years.[11 ,12 ]

Immunosuppressive Treatment-Related Kaposi Sarcoma

In 1969, the first case of KS in association with immunosuppression in a renal transplant patient was described. Since that time, a number of renal and other organ allograft recipients who received prednisone and azathioprine developed KS shortly after the onset of immunosuppressive therapy.[13 ] Estimates of the incidence of KS in immunosuppressed renal transplant recipients are between 150 and 200 times the expected incidence of the tumor in the general population. The average time to develop KS after transplantation is 16 months. Although the KS tumor in iatrogenically immunosuppressed patients often remains localized to the skin, widespread dissemination with mucocutaneous or visceral organ involvement is common. In some cases, the KS tumors have regressed as a result of reduction or changes in immunosuppressive therapy. Clinical management of renal transplant patients who develop KS is difficult and requires a balance between the risk of death from generalized KS and the risk of graft rejection and complications of renal failure that may occur if the immunosuppressive therapy is discontinued.

Epidemic Kaposi Sarcoma

In 1981, a fulminant and disseminated form of KS in young homosexual or bisexual men was first reported as part of an epidemic now known as AIDS.[14 ] The etiology of AIDS is a T-cell lymphotropic retrovirus known as HIV. The underlying immunologic deficiency that characterizes HIV disease is an acquired profound disorder of cell-mediated immune functions. This immunologic deficiency and immune dysregulation predisposes the host to a variety of opportunistic infections and unusual neoplasms, especially KS. HIV may play an indirect role in the development of KS.[15 ]

Approximately 95% of all the cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual men. In the past, approximately 26% of all homosexual males with HIV disease presented with, or eventually developed, KS during the course of their illness. By comparison, fewer than 3% of all heterosexual intravenous drug users with HIV disease developed KS. The proportion of HIV disease patients with KS has steadily decreased since the epidemic was first identified in 1981.[16 ] About 48% of AIDS patients in 1981 had KS as their presenting AIDS diagnosis. By August 1987, the cumulative proportion of AIDS patients with KS had diminished to fewer than 20%. The introduction of combined antiretroviral therapy (cART) has delayed or prevented the emergence of drug-resistant HIV strains, profoundly decreased viral load, led to increased survival, and lessened the risk of opportunistic infections.[17 ,18 ,19 ] The use of cART has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[20 ,21 ,22 ,23 ,24 ,25 ]

The lesions that develop may involve the skin; oral mucosa; lymph nodes; and visceral organs, such as the gastrointestinal tract, lung, liver, and spleen. Most patients with HIV disease who present with the mucocutaneous lesions of KS feel healthy and are usually free of systemic symptoms, as compared with HIV patients who first develop an opportunistic infection. The sites of disease at presentation of epidemic KS are much more varied than the sites seen in other types of this neoplasm. In an early report on the clinical manifestations of the disease, 49 patients were described.[26 ] Of these patients, 8% had no skin involvement, 27% had localized or fewer than five skin lesions, and 63% had innumerable skin lesions widely distributed over the skin surface area. Of these patients, 61% had generalized lymphadenopathy at the time of the first examination. Four of these patients, who had generalized lymphadenopathy in the absence of skin lesions or detectable visceral organ involvement at the time of presentation, were found to have biopsy-proven KS localized to the lymph nodes. In 45% of the patients studied, KS lesions were found in one or more sites along the gastrointestinal tract. Of these patients, 29% had either unexplained fever or unexplained weight loss when first seen. While most patients present with skin disease, KS involvement of lymph nodes or the gastrointestinal tract may occasionally precede the appearance of the cutaneous lesions.

Eventually, most patients with epidemic KS develop disseminated disease. The disease often progresses in an orderly fashion from a few localized or widespread mucocutaneous lesions to more numerous lesions and generalized skin disease with lymph node, gastrointestinal tract disease, and other organ involvement. Pleuropulmonary KS is an ominous sign usually occurring late in the course of the disease, especially in those patients whose death is directly attributed to KS.[27 ] Most patients with epidemic KS die of one or more complicating opportunistic infections.

Nonepidemic Gay-Related Kaposi Sarcoma

Several reports documented KS in homosexual men who persistently had no evidence of HIV infection. These patients had an indolent and cutaneous form of the disease, which caused new lesions to appear every few years. Lesions occur most commonly on the extremities and genitalia but can occur anywhere on the skin.[1 ] These cases may indicate the presence of causal factors other than HIV that homosexual men may be exposed to because of their lifestyle.

References:

1. Friedman-Kien AE, Saltzman BR, Cao YZ, et al.: Kaposi's sarcoma in HIV-negative homosexual men. Lancet 335 (8682): 168-9, 1990.
2. Safai B: Kaposi's sarcoma and acquired immunodeficiency syndrome. In: DeVita VT, Hellman S, Rosenberg S, eds.: AIDS: Etiology, Diagnosis, Treatment and Prevention. 4th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 295-318.
3. Chang Y, Cesarman E, Pessin MS, et al.: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266 (5192): 1865-9, 1994.
4. Moore PS, Chang Y: Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med 332 (18): 1181-5, 1995.
5. Su IJ, Hsu YS, Chang YC, et al.: Herpesvirus-like DNA sequence in Kaposi's sarcoma from AIDS and non-AIDS patients in Taiwan. Lancet 345 (8951): 722-3, 1995.
6. Gao SJ, Kingsley L, Li M, et al.: KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 2 (8): 925-8, 1996.
7. Chang Y, Ziegler J, Wabinga H, et al.: Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group. Arch Intern Med 156 (2): 202-4, 1996.
8. Safai B, Good RA: Kaposi's sarcoma: a review and recent developments. Clin Bull 10 (2): 62-9, 1980.
9. Reynolds WA, Winkelmann RK, Soule EH: Kaposi's sarcoma: a clinicopathologic study with particular reference to its relationship to the reticuloendothelial system. Medicine (Baltimore) 44 (5): 419-43, 1965.
10. Safai B, Miké V, Giraldo G, et al.: Association of Kaposi's sarcoma with second primary malignancies: possible etiopathogenic implications. Cancer 45 (6): 1472-9, 1980.
11. Taylor JF, Templeton AC, Vogel CL, et al.: Kaposi's sarcoma in Uganda: a clinico-pathological study. Int J Cancer 8 (1): 122-35, 1971.
12. Templeton AC, Bhana D: Prognosis in Kaposi's sarcoma. J Natl Cancer Inst 55 (6): 1301-4, 1975.
13. Penn I: Kaposi's sarcoma in organ transplant recipients: report of 20 cases. Transplantation 27 (1): 8-11, 1979.
14. Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men--New York City and California. MMWR Morb Mortal Wkly Rep 30 (25): 305-8, 1981.
15. Vogel J, Hinrichs SH, Reynolds RK, et al.: The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335 (6191): 606-11, 1988.
16. Selik RM, Starcher ET, Curran JW: Opportunistic diseases reported in AIDS patients: frequencies, associations, and trends. AIDS 1 (3): 175-82, 1987.
17. Flexner C: HIV-protease inhibitors. N Engl J Med 338 (18): 1281-92, 1998.
18. Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338 (13): 853-60, 1998.
19. Lodi S, Guiguet M, Costagliola D, et al.: Kaposi sarcoma incidence and survival among HIV-infected homosexual men after HIV seroconversion. J Natl Cancer Inst 102 (11): 784-92, 2010.
20. Portsmouth S, Stebbing J, Gill J, et al.: A comparison of regimens based on non-nucleoside reverse transcriptase inhibitors or protease inhibitors in preventing Kaposi's sarcoma. AIDS 17 (11): F17-22, 2003.
21. International Collaboration on HIV and Cancer: Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 92 (22): 1823-30, 2000.
22. Dupont C, Vasseur E, Beauchet A, et al.: Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodéficience humaine. AIDS 14 (8): 987-93, 2000.
23. Tam HK, Zhang ZF, Jacobson LP, et al.: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer 98 (6): 916-22, 2002.
24. Carrieri MP, Pradier C, Piselli P, et al.: Reduced incidence of Kaposi's sarcoma and of systemic non-hodgkin's lymphoma in HIV-infected individuals treated with highly active antiretroviral therapy. Int J Cancer 103 (1): 142-4, 2003.
25. Grabar S, Abraham B, Mahamat A, et al.: Differential impact of combination antiretroviral therapy in preventing Kaposi's sarcoma with and without visceral involvement. J Clin Oncol 24 (21): 3408-14, 2006.
26. Krigel RL, Laubenstein LJ, Muggia FM: Kaposi's sarcoma: a new staging classification. Cancer Treat Rep 67 (6): 531-4, 1983.
27. Gill PS, Akil B, Colletti P, et al.: Pulmonary Kaposi's sarcoma: clinical findings and results of therapy. Am J Med 87 (1): 57-61, 1989.

Stage Information for Kaposi Sarcoma

The staging evaluation of patients with classic Kaposi sarcoma (KS) should be individualized. The advanced age of most of the patients, localized nature of the tumor, rarity of visceral involvement, and usually indolent course of the disease should temper the extent of the evaluation. A careful examination of the skin and lymph nodes is sufficient in most cases. For the rare patient with rapidly progressive tumor or signs or symptoms of visceral involvement, appropriate evaluation is indicated. No universally accepted classification is available for epidemic KS. Staging schemes that incorporate laboratory parameters as well as clinical features have been proposed. Since most patients with epidemic KS do not die from the disease, factors besides tumor burden are apparently involved in survival.

The conventions used to stage KS and the methods used to evaluate the benefits of KS treatment continue to evolve because of changes in the treatment of human immunodeficiency virus (HIV) and in recognition of deficiencies in standard tumor assessment. The clinical course of KS, the selection of treatment, and the response to treatment are heavily influenced by the degree of underlying immune dysfunction and opportunistic infections.

The AIDS Clinical Trials Group (ACTG) Oncology Committee has published criteria for the evaluation of epidemic KS.[1 ] The staging system incorporates measures of extent of disease, severity of immunodeficiency, and presence of systemic symptoms. As shown in Table 1 below, the ACTG criteria categorizes the extent of the tumor as localized or disseminated, the CD4 cell number as high or low, and a systemic illness as absent or present.

A subsequent prospective analysis of 294 patients entered on ACTG trials for KS between 1989 and 1995 showed that each of the tumor, immune system, and systemic illness variables was independently associated with survival.[2 ] Multivariate analysis showed that immune system impairment was the most important single predictor of survival. In patients with relatively high CD4 counts, tumor stage was predictive. A CD4 count of 150 cells/mm³ may be a better discriminator than the published cutoff of 200 cells/mm³. A study is in progress to determine if viral load adds predictive information. None of the prior studies were conducted at a time when combined antiretroviral therapy (cART) was readily available. The impact of cART on survival in KS requires continued assessment.

Table 1. AIDS Clinical Trials Group Staging Classification

	Good Risk (0)	Poor Risk (1)
	(Any of the following)	(Any of the following)
Tumor (T)	Confined to skin and/or lymph nodes and/or minimal oral diseaseMinimal oral disease is non-nodular KS confined to the palate.	Tumor-associated edema or ulceration
		Extensive oral KS
		Gastrointestinal KS
		KS in other non-nodal viscera
Immune system (I)	CD4 cells ≥ = 200/µL	CD4 cells <200 per cubic mm
Systemic illness (S)	No history of OIs or thrushOIs are opportunistic infections.	History of OIs and/or thrush
	No "B" symptoms "B" symptoms are unexplained fever, night sweats, >10% involuntary weight loss, or diarrhea persisting >2 weeks.	"B" symptoms present
	Performance status ≥70 (Karnofsky)	Performance status <70
		Other HIV-related illness (e.g., neurological disease or lymphoma)

References:

1. Krown SE, Metroka C, Wernz JC: Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 7 (9): 1201-7, 1989.
2. Krown SE, Testa MA, Huang J: AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 15 (9): 3085-92, 1997.

Classic Kaposi Sarcoma Treatment

Classic Kaposi sarcoma (KS) usually is limited to the skin and has an indolent course. Patients with this tumor are predisposed to the development of a second primary malignancy, and the treating physician should consider this factor when arranging a schedule of follow-up treatment for the patient.

Equivalent standard treatment options:

Solitary lesions:

1. Radiation therapy: For solitary lesions or lesions of limited extent, modest doses of radiation applied to the lesions with a limited margin provide excellent control of disease in the treated area. Usually, superficial radiation beams such as electron beams are used. Some authors believe disease recurrence in adjacent, untreated skin is common if only involved-field radiation therapy is used and claim better cure rates when extended-field radiation therapy is used.[1 ,2 ]
   • Low-voltage (100 kv) photon radiation: 8 Gy to 10 Gy given as a single dose or 15 Gy to 20 Gy given over 1 week because solitary lesions control nearly 100% of local disease, but recurrence in adjacent areas is common.
   • Electron-beam radiation therapy (EBRT): 4 Gy given once weekly for 6 to 8 consecutive weeks with a 4-MeV to 6-MeV electron beam. Ports should include the entire skin surface 15 cm above the lesion.
2. Surgical excision may be of benefit in some patients with small superficial lesions, but local recurrence is likely to be a problem. However, over the years, multiple small excisions can be performed to achieve good disease control.

Widespread skin disease:

1. Radiation therapy: Modest doses are effective in controlling disease. The type of radiation (i.e., photon vs. electron) and fields used must be tailored to suit the distribution of disease in the individual patient.[2 ]
   • Extended-field EBRT.
   • For disease limited to areas distal to the knee, subtotal-skin EBRT directed to skin below the umbilicus.
   • For disease that extends above the knee, total-skin EBRT.

   EBRT used in this manner gave long-term results that were superior to those obtained with radiation therapy administered to successive individual lesions as they appeared.[2 ]

   • EBRT: 4 Gy given once weekly for 6 to 8 consecutive weeks, and subtotal- or total-skin radiation therapy given for extensive disease.
2. Chemotherapy: Because classic KS is such a rare disease in the United States and is usually treated initially with radiation therapy, few patients have been treated with chemotherapy, and no randomized prospective trials have compared one agent to another. Several authors have used single-agent vinblastine given as a weekly dose of approximately 0.1 mg/kg.[3 ,4 ,5 ,6 ] Almost all of the patients had good to excellent response. In most cases, patients required prolonged courses of therapy, for several years, to maintain a partial response. Doses of vinblastine were titrated in individual patients to maintain a white blood count of more than 3,000 leukocytes. Follow-up after completion of therapy was not presented. In a multicenter trial of 55 patients who were treated over a decade, a 71% overall response rate was seen using pegylated liposomal doxorubicin.[7 ][Level of evidence: 3iiiDiv] In addition to the positive response rates of pegylated liposomal doxorubicin and the vinca alkaloids, response rates showing a greater than 50% decrease in lesions have also been reported in small, uncontrolled series for etoposide, taxanes, gemcitabine, and interferon alfa.[8 ][Level of evidence: 3iiiDiv]

   One patient was treated repeatedly with intralesional injections of 0.25 to 0.50 mg of vincristine, which resulted in complete disappearance of the treated lesion.[9 ] Multiple courses of therapy were required because of the recurrence of disease in untreated areas.

Electroporation of the skin lesions was combined with intravenous bleomycin for 19 patients with classical KS. Most patients responded after one application, the rest after two or three applications, with a median duration of response of 16 months.[10 ][Level of evidence: 3iiiDiv]

Lymph node and gastrointestinal tract involvement:

1. Chemotherapy: Several patients who had widespread skin disease and were treated with chemotherapy also had lymph node and gastrointestinal tract involvement. The disease in these sites also responded to vinblastine. Trials are required to define therapy. One such trial, MSKCC-04055, has been completed.
2. Local radiation therapy may be added to chemotherapy if individual lesions require urgent therapy.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Hamilton CR, Cummings BJ, Harwood AR: Radiotherapy of Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 12 (11): 1931-5, 1986.
2. Nisce LZ, Safai B, Poussin-Rosillo H: Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma. Cancer 47 (4): 640-4, 1981.
3. Solan AJ, Greenwald ES, Silvay O: Long-term complete remissions of Kaposi's sarcoma with vinblastine therapy. Cancer 47 (4): 637-9, 1981.
4. Tucker SB, Winkelmann RK: Treatment of Kaposi sarcoma with vinblastine. Arch Dermatol 112 (7): 958-61, 1976.
5. Scott WP, Voight JA: Kaposi's sarcoma. Management with vincaleucoblastine. Cancer 19 (4): 557-64, 1966.
6. Klein E, Schwartz RA, Laor Y, et al.: Treatment of Kaposi's sarcoma with vinblastine. Cancer 45 (3): 427-31, 1980.
7. Di Lorenzo G, Kreuter A, Di Trolio R, et al.: Activity and safety of pegylated liposomal doxorubicin as first-line therapy in the treatment of non-visceral classic Kaposi's sarcoma: a multicenter study. J Invest Dermatol 128 (6): 1578-80, 2008.
8. Régnier-Rosencher E, Guillot B, Dupin N: Treatments for classic Kaposi sarcoma: a systematic review of the literature. J Am Acad Dermatol 68 (2): 313-31, 2013.
9. Odom RB, Goette DK: Treatment of cutaneous Kaposi's sarcoma with intralesional vincristine. Arch Dermatol 114 (11): 1693-4, 1978.
10. Di Monta G, Caracò C, Benedetto L, et al.: Electrochemotherapy as "new standard of care" treatment for cutaneous Kaposi's sarcoma. Eur J Surg Oncol 40 (1): 61-6, 2014.

Immunosuppressive Therapy-Related Kaposi Sarcoma Treatment

Some patients with Kaposi Sarcoma (KS) have noted spontaneous and lasting remissions following discontinuation of immunosuppressive therapy. In managing these patients, if immunosuppressive therapy is not critical, its discontinuation is a reasonable first step.

Standard treatment options:

1. Discontinue immunosuppressive therapy (often results in tumor regression). This option is critically important in patients who are receiving immunosuppressive drugs, as in the case of certain transplant patients.
2. Radiation therapy (for disease limited to skin).[1 ,2 ,3 ,4 ]
3. Chemotherapy (single or multiple drug): Most systemic chemotherapy trials in KS patients have been carried out in the African and epidemic varieties. See the section on the treatment of Epidemic Kaposi Sarcoma. The applicability of the results of these trials to KS in immunosuppressed patients is unknown.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Cohen L: Dose, time, and volume parameters in irradiation therapy of Kaposi's sarcoma. Br J Radiol 35 (415): 485-488, 1962.
2. Hamilton CR, Cummings BJ, Harwood AR: Radiotherapy of Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 12 (11): 1931-5, 1986.
3. Lo TC, Salzman FA, Smedal MI, et al.: Radiotherapy for Kaposi's sarcoma. Cancer 45 (4): 684-7, 1980.
4. Nisce LZ, Safai B, Poussin-Rosillo H: Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma. Cancer 47 (4): 640-4, 1981.

Epidemic Kaposi Sarcoma Treatment

Treatment may result:

1. In a disappearance or reduction in size of specific skin lesions, thereby alleviating the discomfort associated with the chronic edema and ulcerations that often accompany multiple skin tumors seen on the lower extremities.
2. In control of symptoms associated with mucosal or visceral lesions.

No data are available, however, to show that treatment improves survival.[1 ] In addition to antitumor treatment, essential components of an optimal Kaposi sarcoma (KS) treatment strategy include combined antiretroviral treatment (cART), prophylaxis for opportunistic infections, and rapid recognition and treatment of intercurrent infections.

Most good-risk patients, defined by the AIDS Clinical Trials Group as T0, show tumor regression with cART alone.[2 ,3 ,4 ] Poor-risk patients, defined as T1, usually require a combination of cART and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion.[2 ,3 ,4 ] The combination of cART and liposomal doxorubicin resulted in a 5-year overall survival (OS) rate of 85% in 140 patients with T1 disease.[3 ][Level of evidence: 3iiiDiv]

Local modalities

Small localized lesions of KS may be treated by electrodesiccation and curettage, cryotherapy, or by surgical excision. KS tumors are also generally very responsive to local radiation therapy, and excellent palliation has been obtained with doses at 20 Gy or slightly higher.[5 ,6 ,7 ] One report demonstrated a response rate higher than 90%, with a median time to progression of 21 months. Although no difference in response was noted with a variety of fractionation regimens, a single fraction of 8 Gy is indicated for cutaneous lesions and is associated with significantly fewer severe reactions.[8 ] Radiation therapy is generally reserved to treat localized areas of the skin and oral cavity. It is less often used to control pulmonary, gastrointestinal tract, or other sites of KS lesions. Localized KS lesions have also been effectively treated with intralesional injections of vinblastine.[9 ] Alitretinoin 0.1% gel provided local control in a randomized prospective multicenter trial.[10 ][Level of evidence: 1iiDiv]

Chemotherapy

In epidemic KS, the already profoundly depressed immunologic status of the host limits the therapeutic usefulness of systemic chemotherapy. Systemic chemotherapy studies in epidemic KS have used as single agents or in combinations doxorubicin, bleomycin, vinblastine, vincristine, etoposide, paclitaxel, and docetaxel.[11 ,12 ,13 ,14 ,15 ][Level of evidence: 3iiiDiv] The combination of cART and liposomal doxorubicin resulted in a 5-year OS of 85% in 140 patients with T1 disease.[3 ][Level of evidence: 3iiiDiv]

Randomized multicenter trials showed an improvement in response rate (45%-60% vs. 20%-25%) and a more favorable toxic effects profile for pegylated liposomal doxorubicin or liposomal daunorubicin, compared to the combination of doxorubicin, bleomycin, and vincristine or bleomycin and vincristine.[16 ,17 ,18 ][Level of evidence: 1iiDiv] During cART, both pegylated liposomal doxorubicin and paclitaxel are active single agents with response rates close to 50%.[19 ][Level of evidence: 1iiDiv]

Biologic and targeted therapy

The interferon alphas have also been widely studied and show a 40% objective response rate in patients with epidemic KS.[20 ,21 ] In these reports, the responses differed significantly according to the prognostic factors of extent of disease, prior or coexistent opportunistic infections, prior treatment with chemotherapy, CD4 lymphocyte counts lower than 200 cells/mm³, the presence of circulating acid-labile interferon alpha, and an increase in beta-2-microglobulin. Several treatment studies have combined interferon alpha with other chemotherapeutic agents. Overall, these trials have shown no benefit with the interferon-chemotherapy combinations as compared to the single-agent activities.

Recombinant interferon alpha-2a and interferon alpha-2b were the first agents approved for the treatment of KS. Approval was based on single-agent studies performed in the 1980s before the advent of antiretroviral therapy. The early studies demonstrated improved efficacy at relatively high doses. High-dose monotherapy is rarely used today, and instead, interferon is given in combination with other anti-HIV drugs in doses of 4 to 18 million units. Neutropenia is dose limiting, and trials of doses of 1 to 10 million units combined with less myelosuppressive antiretrovirals are in progress. Response to interferon is slow, and the maximum effect is seen after 6 or more months. Interferon should probably not be used in the treatment of patients with rapidly progressive, symptomatic KS.

Imatinib, a c-kit/PDGF (platelet-derived growth factor) receptor inhibitor, resulted in partial responses in 10 of 30 previously treated patients (cART + chemotherapy).[22 ]

Bevacizumab, the humanized, antivascular, endothelial growth-factor monoclonal antibody, had a response rate in 5 of 16 patients who did not improve after the institution of cART and chemotherapy.[23 ][Level of evidence: 3iiiDiv]

Interleukin-12 had a response rate of 71% (95% confidence interval, 48%-89%) among 24 evaluable patients in a phase I and phase II trial.[24 ][Level of evidence: 3iiiDiv]

Treatment options under clinical evaluation:

• Patients with epidemic KS are appropriate candidates for clinical trials evaluating new drugs or biologicals.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Safai B: Kaposi's sarcoma and acquired immunodeficiency syndrome. In: DeVita VT, Hellman S, Rosenberg S, eds.: AIDS: Etiology, Diagnosis, Treatment and Prevention. 4th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 295-318.
2. Krown SE: Highly active antiretroviral therapy in AIDS-associated Kaposi's sarcoma: implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi's sarcoma. J Clin Oncol 22 (3): 399-402, 2004.
3. Bower M, Dalla Pria A, Coyle C, et al.: Prospective stage-stratified approach to AIDS-related Kaposi's sarcoma. J Clin Oncol 32 (5): 409-14, 2014.
4. Krell J, Stebbing J: Broader implications of a stage-guided stratified therapeutic approach for AIDS-related Kaposi's sarcoma. J Clin Oncol 32 (5): 373-5, 2014.
5. Cooper JS, Steinfeld AD, Lerch I: Intentions and outcomes in the radiotherapeutic management of epidemic Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 20 (3): 419-22, 1991.
6. Nobler MP, Leddy ME, Huh SH: The impact of palliative irradiation on the management of patients with acquired immune deficiency syndrome. J Clin Oncol 5 (1): 107-12, 1987.
7. Singh NB, Lakier RH, Donde B: Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma--a prospective randomized trial. Radiother Oncol 88 (2): 211-6, 2008.
8. Berson AM, Quivey JM, Harris JW, et al.: Radiation therapy for AIDS-related Kaposi's Sarcoma. Int J Radiat Oncol Biol Phys 19 (3): 569-75, 1990.
9. Epstein JB, Lozada-Nur F, McLeod WA, et al.: Oral Kaposi's sarcoma in acquired immunodeficiency syndrome. Review of management and report of the efficacy of intralesional vinblastine. Cancer 64 (12): 2424-30, 1989.
10. Bodsworth NJ, Bloch M, Bower M, et al.: Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's sarcoma. Am J Clin Dermatol 2 (2): 77-87, 2001.
11. Evans SR, Krown SE, Testa MA, et al.: Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study. J Clin Oncol 20 (15): 3236-41, 2002.
12. Saville MW, Lietzau J, Pluda JM, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 346 (8966): 26-8, 1995.
13. 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 103 (2): 417-21, 2005.
14. Gill PS, Tulpule A, Espina BM, et al.: Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma. J Clin Oncol 17 (6): 1876-83, 1999.
15. Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al.: Management of AIDS-related Kaposi's sarcoma. Lancet Oncol 8 (2): 167-76, 2007.
16. Stewart S, Jablonowski H, Goebel FD, et al.: Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group. J Clin Oncol 16 (2): 683-91, 1998.
17. Northfelt DW, Dezube BJ, Thommes JA, et al.: Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol 16 (7): 2445-51, 1998.
18. Gill PS, Wernz J, Scadden DT, et al.: Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol 14 (8): 2353-64, 1996.
19. Cianfrocca M, Lee S, Von Roenn J, et al.: Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer 116 (16): 3969-77, 2010.
20. Real FX, Oettgen HF, Krown SE: Kaposi's sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol 4 (4): 544-51, 1986.
21. Groopman JE, Gottlieb MS, Goodman J, et al.: Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med 100 (5): 671-6, 1984.
22. Koon HB, Krown SE, Lee JY, et al.: Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol 32 (5): 402-8, 2014.
23. Uldrick TS, Wyvill KM, Kumar P, et al.: Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol 30 (13): 1476-83, 2012.
24. Little RF, Pluda JM, Wyvill KM, et al.: Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 107 (12): 4650-7, 2006.

Recurrent Kaposi Sarcoma Treatment

The prognosis for any treated Kaposi sarcoma patient with progressing, recurring, or relapsing disease is highly variable. Deciding on further treatment depends on many factors, most importantly the clinical setting (i.e., classic, immunosuppressive treatment, or AIDS) in which the tumor arises as well as individual patient considerations.

Clinical trials are appropriate and should be considered when possible.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (10 / 01 / 2015)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Classic Kaposi Sarcoma Treatment

Added text to state that electroporation of the skin lesions was combined with intravenous bleomycin for 19 patients with classical KS. Also added that most patients responded after one application, the rest after two or three applications, with a median duration of response of 16 months (cited Di Monta et al. as reference 10 and level of evidence 3iiiDiv).

Epidemic Kaposi Sarcoma Treatment

Revised text to state that most good-risk patients, defined by the AIDS Clinical Trials Group as T0, show tumor regression with combined antiretroviral therapy (cART) alone. Also revised text to state that poor-risk patients, defined as T1, usually require a combination of cART and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion (cited Krell et al. as reference 4). Added that the combination of cART and liposomal doxorubicin resulted in a 5-year overall survival rate (OS) of 85% in 140 patients with T1 disease (cited Bower et al. as reference 3 and level of evidence 3iiiDiv).

Added text to state that the combination of cART and liposomal doxorubicin resulted in a 5-year OS of 85% in 140 patients with T1 disease (cited level of evidence 3iiiDiv).

Revised subheading to read Biologic and targeted therapy.

Added text to state that imatinib, a c-kit/PDGF (platelet-derived growth factor) receptor inhibitor, resulted in partial responses in 10 of 30 previously treated patients (cited Koon et al. as reference 22).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Kaposi sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Kaposi Sarcoma Treatment are:

• Eric J. Seifter, MD (Johns Hopkins University)
• Minh Tam Truong, MD (Boston University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Kaposi Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/kaposi-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389335]

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Disclaimer

Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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Last Revised: 2015-10-01