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Kaposi sarcoma
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 herpesvirus (KSHV) or human herpesvirus 8 (HHV8), predominantly transmitted via saliva but also by solid organ transplantation. In the United States, epidemic or acquired immunodeficiency syndrome (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 KSs are also encountered. Therapy is similar for each type.
Management Strategy
Therapy goals include cosmetic improvement, palliation, or cessation of progression. 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 decreased dosing of the immunosuppressive regimen or change 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 antiangiogenic agents, antiviral agents, matrix metalloproteinase inhibitors, tyrosine kinase inhibitors, laser therapy, PD-1 inhibitors, and agents targeting interleukin (IL)-12 .
Specific Investigations
Management of AIDS-related Kaposi’s sarcoma
Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al. Lancet Oncol 2007; 8: 167–76.
Review of current treatment strategies and ongoing investigations.
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, et al.; Caelyx/KS Spanish Group. AIDS 2004; 18: 1737–40.
Randomized study comparing pegylated liposomal doxorubicin plus ART vs. ART alone showed a greater response rate in the former group.
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, et al. JAIDS 2012; 60: 150–7.
Fifty-nine treatment-naive 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.
Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma
Cianfrocca M, Lee S, Von Roenn J, et al. Cancer 2010; 116: 3969–77.
Seventy-three patients with advanced HIV-associated KS were randomized to paclitaxel vs. 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.
In patients with early disease (stage T 0 ), 80% of patients who had not previously received ART showed regression with ART alone.
Imiquimod 5% cream versus cryotherapy in classic Kaposi sarcoma
Odvakmaz DE, Bayramugurler D, Caglayan C. J Cutan Med Surg 2019; 23: 488–95.
Single-blinded, non-controlled study. Of the patients receiving cryotherapy, 50% had complete response compared with 42.3% in the imiquimod group.
Radiotherapy in the management of classic Kaposi sarcoma: a single institution experience in northeast Turkey
Kandaz M, Bahat Z, Guler OC. Dermatol Ther 2018; 31: e12605.
For non-HIV–associated KS, the complete response rate at 5 years was 91.6% for radiotherapy with >20 Gy and 89.6% with 8 Gy.
Phase III vehicle-controlled, multicentered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi’s sarcoma
Bodsworth NJ, Bloch M, Bower M, et al.; International Panretin Gel KS Study Group. Am J Clin Dermatol 2001; 2: 77–87.
Response rate was 37% (compared with 7% treated with vehicle).
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, et al. AIDS 2006; 41: 149–53.
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, et al. 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
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A pilot study of liposomal doxorubicin combined with bevacizumab followed by bevacizumab monotherapy in patients with advanced Kaposi sarcoma
Ramaswami R, Uldrick TS, Polizzotto MN, et al. Clin Cancer Res 2019; 25: 4238–47.
Sixteen patients were treated with bevacizumab and liposomal doxorubicin, followed by bevacizumab monotherapy maintenance. Overall response rate was 56%, with a median time to response of 1.5 years.
A phase Ib study of sorafenib (BAY 43-9006) in patients with Kaposi sarcoma
Uldrick TS, Goncalves PH, Wyvill KM, et al. Oncologist 2017; 22(5): 505–49.
Minimal clinical response with only 2/7 patients experiencing a partial response.
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