Epidemic Kaposi Sarcoma
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Treatment may result:
- 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.
- 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 highly active antiretroviral
treatment (HAART), prophylaxis for opportunistic infections, and rapid recognition and
treatment 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 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 not much larger than 20 Gy.[3,4] 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.[5]
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.[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 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.[8-12][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.[13-15][Level of evidence: 1iiDiv]
Biologic therapy
The interferon alphas have also been widely studied and show a 40% objective
response rate in patients with epidemic KS.[16,17] 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.
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 trials
evaluating 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
-
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.
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Saville MW, Lietzau J, Pluda JM, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 346 (8966): 26-8, 1995.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al.: Management of AIDS-related Kaposi's sarcoma. Lancet Oncol 8 (2): 167-76, 2007.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Little RF, Pluda JM, Wyvill KM, et al.: Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 107 (12): 4650-7, 2006.
[PUBMED Abstract]
Back to Top
< Previous Section | Next Section > |