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Kaposi Sarcoma Treatment (PDQ®)

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Kaposi sarcoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Epidemiology and clinical presentation.
• Cellular classification.
• Staging.
• Treatment options for different types of tumor.

This summary 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.

Some of the reference citations in the 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. Based on the strength of the available evidence, treatment options are described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

General Information About Kaposi Sarcoma

Kaposi sarcoma (KS) was first described in 1872 by the Hungariandermatologist, Moritz Kaposi. From that time until the current humanimmunodeficiency virus (HIV) disease epidemic identified with the AcquiredImmunodeficiency Syndrome (AIDS), KS remained a rare tumor. While most of thecases seen in Europe and North America have occurred in elderly men of Italianor Eastern European Jewish ancestry, the neoplasm also occurs in several otherdistinct populations: young black African adult males, prepubescent children,renal allograft recipients, and other patients receiving immunosuppressivetherapy. The disseminated, fulminant form of KS associated with HIV disease isreferred to as epidemic KS to distinguish it from the classic, African, andtransplant-related varieties of the neoplasm. In addition, KS has beenidentified in homosexual men apart from the HIV disease epidemic.[1]

Althoughthe histopathology of the different types of the Kaposi tumor is essentiallyidentical in all of these groups, the clinical manifestations and course of thedisease differ dramatically.[2] A key piece to the puzzle of KS pathogenesiswas 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 identifiedin KS tissue biopsies from virtually all patients with classic, African,transplant-related, and AIDS-associated KS but was absent from noninvolvedtissue.[4,5,6,7]

Classic Kaposi Sarcoma

Considered a rare disease, classic KS occurs more often in males, with a ratioof 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 tumorsusually present with one or more asymptomatic red, purple, or brown patches,plaques, or nodular skin lesions. The disease is often limited to single ormultiple lesions usually localized to one or both lower extremities, especiallyinvolving the ankles and soles.

Classic KS most commonly runs arelatively benign, indolent course for 10 to 15 years or more, with slowenlargement of the original tumors and the gradual development of additionallesions. Venous stasis and lymphedema of the involved lower extremity arefrequent complications. In long-standing cases, systemic lesions can developalong the gastrointestinal tract, in lymph nodes, and in other organs. Thevisceral lesions are generally asymptomatic and are most often discovered onlyat 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 innative populations in equatorial Africa and comprised approximately 9% of allcancers seen in Ugandan males. African KS is seen as either an indolentneoplasm identical to the classic disease seen in Europe and North America oras an aggressive disease with fungating and exophytic tumors that may invadethe subcutaneous and surrounding tissue including the underlying bone. InAfrica, both the indolent and locally more aggressive forms of KS occur with amale-to-female ratio comparable to that observed with the classic KS tumor seenin North America and Europe. In general, however, patients in Africa aresignificantly younger than their European counterparts. A lymphadenopathicform of KS is also seen in Africa, primarily in prepubescent children(male:female ratio 3:1). In these cases, the generalized lymphadenopathy isfrequently associated with visceral organ involvement. The prognosis is verypoor 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 renaltransplant patient was described. Since that time, a number of renal and otherorgan allograft recipients who received prednisone and azathioprine developedKS shortly after the onset of immunosuppressive therapy.[13] Estimates of the incidence ofKS in immunosuppressed renal transplant recipients are between 150 and 200 times the expected incidence of the tumor in the generalpopulation. The average time to develop KS after transplantation is 16months. Although the KS tumor in iatrogenically immunosuppressed patientsoften remains localized to the skin, widespread dissemination withmucocutaneous or visceral organ involvement is common. In some cases, the KStumors have regressed as a result of reduction or changes in immunosuppressivetherapy. Clinical management of renal transplant patients who develop KS isdifficult and requires a balance between the risk of death from generalized KSand the risk of graft rejection and complications of renal failure that mayoccur if the immunosuppressive therapy is discontinued.

Epidemic Kaposi Sarcoma

In 1981, a fulminant and disseminated form of KS in young homosexual orbisexual 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. Theunderlying immunologic deficiency that characterizes HIV disease is an acquiredprofound disorder of cell-mediated immune functions. This immunologicdeficiency and immune dysregulation predisposes the host to a variety ofopportunistic infections and unusual neoplasms, especially KS. HIV mayplay an indirect role in the development of KS.[15]

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

The lesions that develop may involve the skin; oral mucosa; lymphnodes; and visceral organs, such as the gastrointestinal tract, lung, liver, andspleen. Most patients with HIV disease who present with the mucocutaneouslesions of KS feel healthy and are usually free of systemic symptoms, ascompared to patients with HIV disease who first develop an opportunisticinfection. The sites of disease at presentation of epidemic KS are much morevaried than the sites seen in other types of this neoplasm. In an early reporton the clinical manifestations of the disease, 49 patients were described.[25] Of these patients, 8% had no skin involvement, 27% had localized or fewer than five skinlesions, and 63% had innumerable skin lesions widely distributed over the skinsurface area. Of these patients, 61% had generalizedlymphadenopathy at the time of the first examination. Four of these patients,who had generalized lymphadenopathy in the absence of skin lesions ordetectable visceral organ involvement at the time of presentation, were found tohave biopsy-proven KS localized to the lymph nodes. In 45% of the patientsstudied, KS lesions were found in one or more sites along the gastrointestinaltract. Of these patients, 29% had either unexplained fever orunexplained weight loss when first seen. While most patients present with skindisease, KS involvement of lymph nodes or the gastrointestinal tract mayoccasionally 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 orwidespread mucocutaneous lesions to more numerous lesions and generalized skin diseasewith lymph node, gastrointestinal tract disease, and other organ involvement. Pleuropulmonary KS is an ominous sign usually occurring late in the course ofthe disease, especially in those patients whose death is directly attributed toKS.[26] Most patients with epidemic KS die of one or more complicatingopportunistic infections.

Nonepidemic Gay-Related Kaposi Sarcoma

Several reports documented KS in homosexual men whopersistently had no evidence of HIV infection. These patients had anindolent and cutaneous form of the disease, which caused new lesions to appear everyfew years. Lesions occur most commonly on the extremities and genitalia butcan occur anywhere on the skin.[1] These cases may indicate the presence ofcausal 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. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. Krigel RL, Laubenstein LJ, Muggia FM: Kaposi's sarcoma: a new staging classification. Cancer Treat Rep 67 (6): 531-4, 1983.
26. 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 beindividualized. The advanced age of most of the patients, localized natureof the tumor, rarity of visceral involvement, and usually indolent course ofthe disease should temper the extent of the evaluation. A careful examinationof the skin and lymph nodes is sufficient in most cases. For the rare patient with rapidly progressive tumor or signs or symptoms of visceralinvolvement, appropriate evaluation is indicated. No universallyaccepted classification is available for epidemic KS. Staging schemes that incorporate laboratory parameters as well as clinical features have been proposed. Sincemost 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 benefitsof KS treatment continue to evolve because of changes inthe treatment of HIV and in recognition of deficiencies in standard tumorassessment. The clinical course of KS, the selection of treatment, andthe response to treatment are heavily influenced by the degree of underlying immunedysfunction and opportunistic infections.

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

A subsequent prospective analysis of294 patients entered on ACTG trials for KS between 1989 and 1995 showed thateach of the tumor, immune system, and systemic illness variables wasindependently associated with survival.[2] Multivariate analysis showed thatimmune system impairment was the most important single predictor of survival. In patients with relatively high CD4 counts, tumor stage was predictive. A CD4count of 150 cells/mm³ may be a better discriminator than thepublished cutoff of 200 cells/mm³. A study is in progress todetermine if viral load adds predictive information. None of the prior studies were conducted at a time when highly activeantiretroviral therapy (HAART) was readily available. The impact of HAART onsurvival in KS requires continued assessment.

AIDS Clinical Trials Group Staging Classification

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

Note: Some citations in the text of this section are followed by a level ofevidence. The PDQ editorial boards use a formal ranking system to help thereader judge the strength of evidence linked to the reported results of atherapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for moreinformation.)

Classic Kaposi sarcoma (KS) usually is limited to the skin and has an indolentcourse. Patients with this tumor are predisposed to the development of asecond primary malignancy, and the treating physician should consider thisfactor 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 limitedmargin provide excellent control of disease in the treated area. Usually,superficial radiation beams such as electron beams are used. Some authors believe diseaserecurrence in adjacent, untreated skin is common ifonly involved-field radiation therapy is used and claim better curerates when extended-field radiation therapy is used.[1,2]
   • Low-voltage (100 kv) photon radiation: 8 Gy to 10 Gy given as a single doseor 15 Gy to 20 Gy given over 1 week because solitary lesions control nearly100% 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 weekswith a 4-MeV to 6-MeV electron beam. Ports should include the entire skinsurface 15 cm above the lesion.
2. Surgical excision may be of benefit in some patients with small superficiallesions, but local recurrence is likely to be a problem. However, over the years, multiplesmall excisions can be performed to achieve good diseasecontrol.

WIDESPREAD SKIN DISEASE:

1. Radiation therapy: Modest doses are effective in controlling disease. Thetype of radiation (i.e., photon vs. electron) and fields used must betailored to suit the distribution of disease in the individual patient.[2]
   • Extended-field EBRT.
   • Fordisease 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 tothose obtained with radiation therapy administered to successive individual lesions as theyappeared.[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 inthe United States and is usually treated initially with radiation therapy, fewpatients have been treated with chemotherapy, and no randomized prospectivetrials have compared one agent to another. Several authors have usedsingle-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, tomaintain a partial response. Doses of vinblastine were titrated in individualpatients to maintain a white blood count of more than 3,000 leukocytes. Follow-up aftercompletion 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: 3iiiDiii]

   One patient was treated repeatedly with intralesional injections of 0.25to 0.50 mg of vincristine, which resulted in complete disappearance of the treated lesion.[8] Multiple courses of therapy were required because of the recurrence of disease inuntreated areas.

LYMPH NODE AND GASTROINTESTINAL TRACT INVOLVEMENT:

1. Chemotherapy: Several patients who had widespread skin disease and were treated with chemotherapy also had lymphnode and gastrointestinal tract involvement. The disease in these sites also responded tovinblastine. No studies are otherwise available to address the treatment ofvisceral classic KS specifically.
2. Local radiation therapy may be added to chemotherapy if individual lesionsrequire urgent therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with classic Kaposi sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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. Odom RB, Goette DK: Treatment of cutaneous Kaposi's sarcoma with intralesional vincristine. Arch Dermatol 114 (11): 1693-4, 1978.

Immunosuppressive Treatment-Related Kaposi Sarcoma

Some patients with Kaposi Sarcoma (KS) have noted spontaneous and lastingremissions 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 receivingimmunosuppressive 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 inKS patients have been carried out in the African and epidemicvarieties. See the section on the treatment of Epidemic Kaposi Sarcoma. Theapplicability of the results of these trials to KS inimmunosuppressed patients is unknown.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with immunosuppressive treatment related Kaposi sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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

Note: Some citations in the text of this section are followed by a level ofevidence. The PDQ editorial boards use a formal ranking system to help thereader judge the strength of evidence linked to the reported results of atherapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for moreinformation.)

Treatment may result:

1. In a disappearance or reduction in size of specific skinlesions, thereby alleviating the discomfort associated with the chronic edemaand ulcerations that often accompany multiple skin tumors seen on the lowerextremities.
2. In control of symptoms associated with mucosal or viscerallesions.

No data are available, however, to show that treatment improvessurvival.[1] In addition to antitumor treatment, essential components of anoptimal Kaposi sarcoma (KS) treatment strategy include highly active antiretroviraltreatment (HAART), prophylaxis for opportunistic infections, and rapid recognition andtreatment of intercurrent infections.

Most good-risk patients, as defined by the AIDS Clinical Trials Group, show tumor regression with HAART alone.[2] Poor-risk patients usually require a combination of HAART and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion.[2]

LOCAL MODALITIES

Small localized lesions of KS may be treated by electrode siccation andcurettage cryotherapy or by surgical excision. KS tumors are also generallyvery responsive to local radiation therapy, and excellent palliation has beenobtained with doses not much larger than 20 Gy.[3,4] One reportdemonstrated a response rate higher than 90%, with a median time to progressionof 21 months. Although no difference in response was noted with a variety offractionation regimens, a single fraction of 8 Gy is indicated for cutaneouslesions and is associated with significantly fewer severe reactions.[5] Radiation therapy is generally reserved to treat localized areas of the skinand oral cavity. It is less often used to control pulmonary, gastrointestinaltract, or other sites of KS lesions. Localized KS lesions have alsobeen effectively treated with intralesional injections of vinblastine.[6]Alitretinoin 0.1% gel provided local control in a randomized prospective multicenter trial.[7][Level of evidence: 1iiDiv]

CHEMOTHERAPY

In epidemic KS, the already profoundly depressed immunologic status of the hostlimits the therapeutic usefulness of systemic chemotherapy. Systemicchemotherapy studies in epidemic KS have used as single agents or incombinations doxorubicin, bleomycin, vinblastine, vincristine, etoposide, paclitaxel, and docetaxel.[8,9,10,11,12][Level of evidence: 3iiiDiv]

Randomized multicenter trialsshowed an improvement in response rate (45% to 60% vs. 20% to 25%) and a more favorable toxic effectsprofile for pegylated liposomal doxorubicin or liposomal daunorubicin, compared to the combination of doxorubicin, bleomycin, and vincristine or bleomycin and vincristine.[13,14,15][Level of evidence: 1iiDiv]

BIOLOGIC THERAPY

The interferon alphas have also been widely studied and show a 40% objectiveresponse rate in patients with epidemic KS.[16,17] In these reports, theresponses differed significantly according to the prognostic factors of extentof disease, prior or coexistent opportunistic infections, prior treatment withchemotherapy, CD4 lymphocyte counts lower than 200 cells/mm³,the presence of circulating acid-labile interferon alpha, and an increase inbeta-2-microglobulin. Several treatment studies have combined interferon alphawith other chemotherapeutic agents. Overall, these trials have shown nobenefit with the interferon-chemotherapy combinations as compared to thesingle-agent activities.

Recombinant interferon alpha-2a and interferon alpha-2b were the first agentsapproved for the treatment of KS. Approval was based on single-agent studiesperformed in the 1980s before the advent of antiretroviral therapy. The earlystudies demonstrated improved efficacy at relatively high doses. High-dosemonotherapy is rarely used today, and instead, interferon is given incombination 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 unitscombined with less myelosuppressive antiretrovirals are in progress. Responseto 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.

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.[18][Level of evidence: 3iiiDiv]

TREATMENT OPTIONS UNDER CLINICAL EVALUATION:

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

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with AIDS-related Kaposi sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Saville MW, Lietzau J, Pluda JM, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 346 (8966): 26-8, 1995.
10. 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.
11. 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.
12. Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al.: Management of AIDS-related Kaposi's sarcoma. Lancet Oncol 8 (2): 167-76, 2007.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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

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

Clinical trials are appropriate andshould be considered when possible.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent Kaposi sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Get More Information From NCI

CALL 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

CHAT ONLINE

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

WRITE TO US

For more information from the NCI, please write to this address:

SEARCH THE NCI WEB SITE

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our "Best Bets" search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

FIND PUBLICATIONS

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

Changes to This Summary (01/21/2009)

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

Added text about a multicenter trial in which patients showed a positive overall response rate using pegylated liposomal doxorubicin (cited DiLorenzo as reference 7 and level of evidence 3iiiDiii).

More Information

ABOUT PDQ

• PDQ® - NCI's Comprehensive Cancer Database.

  Full description of the NCI PDQ database.

ADDITIONAL PDQ SUMMARIES

• PDQ® Cancer Information Summaries: Adult Treatment

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine

  Information about complementary and alternative forms of treatment for patients with cancer.

IMPORTANT:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Date Last Modified: 2009-01-21