Kaposi sarcoma

Published on 18/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

This article have been viewed 2086 times

114

Kaposi sarcoma

Lindsay A. Eminger and Steven M. Manders

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

Kaposi sarcoma (KS) is a distinct, often multifocal endothelial neoplasm etiologically linked to Kaposi sarcoma herpes virus (KSHV/HHV-8), predominantly transmitted via saliva, but also by solid organ transplantation. In the US, epidemic or AIDS-associated KS is the most common presentation; however, transplant or iatrogenic immunosuppression-related KS is on the increase. In clinical practice, classic and endemic KS are also encountered. Therapy is similar for each type.

Management strategy

Generally, the goals of therapy target cosmetic improvement, palliation, or cessation of progression. For treatment purposes, patients can be divided into several groups. Dermatologists most often encounter limited cutaneous KS, defined as fewer than 10 skin lesions, a lack of oral or visceral involvement, and the absence of tumor-associated lymphedema. Treatment options include cryotherapy, intralesional vinblastine, radiotherapy, and alitretinoin gel. Because treatment is essentially for cosmesis, side effects such as pigmentary changes and pain become important in therapeutic decisions.

For patients with resistant limited disease, extensive cutaneous involvement, systemic KS, or tumor-associated lymphedema, treatment modalities include liposomal anthracyclines (pegylated liposomal doxorubicin or liposomal daunorubicin), taxanes (paclitaxel), and interferon-α. For epidemic KS, effective antiretroviral therapy (ART) can by itself be sufficient to halt disease progression, and has been found to have a synergistic effect with the liposomal anthracyclines, paclitaxel, and interferon-α. However, several cases of worsening of KS with the initiation of ART have been reported, as part of an immune reconstitution syndrome. Iatrogenic immunosuppression-associated KS can respond to a reduction in treatment doses or change in immunosuppressive regimen to sirolimus. Radiotherapy remains an alternative treatment option for this group of patients.

Treatment of oral lesions is problematic because of inaccessibility to cryotherapy and radiation-induced mucositis. Options include intralesional vinblastine, sclerosing agents such as sodium tetradecyl sulfate, or systemic treatments.

An increasing number of investigational therapeutics have been explored for the treatment and prevention of KS, including anti-angiogenic agents, antiviral agents, orally active matrix metalloproteinase inhibitors, tyrosine kinase inhibitors, and agents targeting interleukin (IL)-12.

Specific investigations

Serology for HIV, CD4+ T-lymphocyte counts, viral load (if HIV positive)

Complete blood count, renal and hepatic function

Chest radiograph

Stool for occult blood

Management of AIDS-related Kaposi’s sarcoma.

Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, Di Trolio R, De Placido S, Dezube BJ. Lancet Oncol 2007; 8: 167–76.

Review of current treatment strategies and ongoing investigations.

Update on KSHV epidemiology, Kaposi sarcoma pathogenesis, and treatment of Kaposi sarcoma.

Uldrick TS, Whitby D. Cancer Lett 201; 30: 150–62.

Comprehensive review of KS, including etiology and treatment options.

First-line therapies

Pegylated liposomal doxorubicin	A
Paclitaxel	A
Antiretroviral therapy	B
Cryotherapy	B
Radiotherapy	B
Alitretinoin gel	A

PEGylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi’s sarcoma.

Martin-Carbonero L, Barrios A, Saballs P, Sirera G, Santos J, Palacios R, et al. Caelyx/KS Spanish Group. AIDS 2004; 18: 1737–40.

Randomized study comparing pegylated liposomal doxorubicin (20 mg/m² every 3 weeks) plus ART vs ART alone showed a greater response rate (76% vs 20%, respectively, in the intent-to-treat analysis) in the former group.

Liposomal doxorubicin is currently the chemotherapeutic agent of choice.

A randomized controlled trial of highly active antiretroviral therapy versus highly active antiretroviral therapy and chemotherapy in therapy-naive patients with HIV-associated Kaposi sarcoma in South Africa.

Mosam A, Shaik F, Uldrick TS, Esterhuizen T, Friedland GH, Scadden DT, et al. JAIDS 2012; 60: 150–7.

Fifty-nine treatment-naïve patients were randomized to ART (stavudine, lamivudine, and nevirapine) and 53 to ART and chemotherapy (Triomune plus bleomycin, doxorubicin, and vincristine). Overall KS response was 39% in the ART arm and 66% in the combination therapy arm. There was no survival difference.

Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma.

Tulpule A, Groopman J, Saville MW, Harrington Jr W, Friedman-Kien A, Espina BM, et al. Cancer 2002; 95: 147–54.

Phase II trial of 107 patients showed a complete or partial response with or without concomitant protease inhibitor of 59% and 54%, respectively.

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma.

Cianfrocca M, Lee S, Von Roenn J, Tulpule A, Dezube BJ, Aboulafia DM, et al. Cancer 2010; 116: 3969–77.

Seventy-three patients with advanced-HIV associated KS were randomized to paclitaxel versus pegylated liposomal doxorubicin, both of which resulted in significant improvement of pain and swelling. Overall incidence of toxicity was greater in those treated with paclitaxel.

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.

Krown SE. J Clin Oncol 2004; 22: 399–402.

This article reviews the evidence regarding the use of monotherapy in KS. In patients with early disease (stage T₀), 80% of patients who had not previously received ART showed regression with ART alone.

Cryotherapy for cutaneous Kaposi’s sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial.

Tappero JW, Berger TG, Kaplan LD, Volberding PA, Kahn JO. JAIDS 1991; 4: 839–46.

Subjects received an average of three treatments per lesion resulting in a 70% cosmetic response rate.

Radiotherapy of classic and human immunodeficiency virus-related Kaposi’s sarcoma: results in 1482 lesions.

Caccialanza M, Marca S, Piccinno R, Eulisse G. J Eur Acad Dermatol Venereol 2008; 22: 297–302.

A 98% clearance rate was reported in classic lesions, and a 91% clearance rate in HIV-associated lesions, with good overall tolerability.

Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi’s sarcoma.

Bodsworth NJ, Bloch M, Bower M, Donnell D, Yocum R, International Panretin Gel KS Study Group. Am J Clin Dermatol 2001; 2: 77–87.

Response rate was 37% (compared to 7% treated with vehicle).

Marginal response rate and exorbitant cost make the usefulness of this modality questionable. Tretinoin gel may be a reasonable alternative topical retinoid option (Topical treatment of epidemic Kaposi’s sarcoma with all-trans-retinoic acid. Bonhomme L, Fredj G, Averous S, Szekely AM, Ecstein E, Trumbic B, et al. Ann Oncol 1991; 2: 234–5).

Second-line therapies

Intralesional interferon	C
Interferon-α_2b	C
Intralesional vinblastine	C

Intralesional interferon-alpha and zidovudine in epidemic Kaposi’s sarcoma.

Dupuy J, Prize M, Lynch G, Bruce S, Schwartz M. J Am Acad Dermatol 1993; 28: 966–72.

Intralesional interferon-α (1 million units three times weekly for 6 weeks) showed a response rate of 85%, but this was not statistically significant.

Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial.

Krown SE, Lee JY, Lin L, Fischl MA, Ambinder R, Von Roenn JH. AIDS 2006; 41: 149–53.

The authors observed that the administration of interferon-α_2b led to limited improvement in KS lesions. The maximum tolerated dose was 5 million IU/day.

Intralesional vinblastine for cutaneous Kaposi’s sarcoma associated with acquired immunodeficiency syndrome.

Boudreaux AA, Smith LL, Cosby CD, Bason MM, Tappero JW, Berger TG. J Am Acad Dermatol 1993; 28: 61–5.

Responses were achieved in 88% of treated lesions, but pain and hyperpigmentation are common. Pain was minimized by the addition of bicarbonate-buffered lidocaine to the diluent.

Third-line therapies

Bevacizumab	C
Sorafenib	E
Lenolidamide	E
Thalidomide	B
Liposomal all-trans-retinoic acid, intravenous	B
Photodynamic therapy	B
9-cis-retinoic acid	B
Etoposide	B
mTOR inhibitors (sirolimus/rapamycin)	C
IL-12	C
Matrix metalloproteinase inhibitor (COL-3 [metastat])	C
Halofuginone	C
Imiquimod 5% cream	C
Sodium tetradecyl sulfate 3%	C
Surgical excision	E
Antiviral agents (ganciclovir, valganciclovir, foscarnet)	B
Intramuscular immuneglobulin	E