Treatment of AIDS-associated Kaposi's sarcoma depends on the extent of the disease, how quickly it is progressing, and the presence and severity of symptoms that affect the patient's daily activities and quality of life. The choice of treatment may also be influenced by the severity of the underlying HIV infection and by the presence of any other complications. Management of Kaposi's sarcoma includes antiretroviral therapy (a combination of agents that prevents the virus from reproducing properly) for the HIV infection, as well as therapies to prevent and promptly treat any infections that occur. Treatments that reduce levels of HIV and relieve AIDS symptoms may also decrease the severity of Kaposi's sarcoma lesions. Researchers are not sure whether this is because improved immune function allows the body to control HHV-8 (the virus associated with Kaposi's sarcoma) more effectively, or because control of HIV reduces the levels of certain proteins that stimulate the growth of Kaposi's sarcoma lesions, or both. Drugs used to treat HIV infection may also have a direct effect on Kaposi's sarcoma lesions and slow their growth. Local Therapies
Systemic Chemotherapy & Biologic TherapyWhen lesions are extensive, involve internal organs, or cause lymphedema (a condition in which excess fluid collects in tissue and causes swelling), doctors may administer chemotherapy drugs intravenously. The most commonly used drugs are liposomal doxorubicin and paclitaxel. Physicians at Memorial Sloan-Kettering began using interferon alpha to treat Kaposi's sarcoma in the early 1980s.1 This drug inhibits some of the growth factors associated with Kaposi's sarcoma, and in laboratory experiments it inhibits both HIV and HHV-8 as well. Responses to interferon alpha can occur slowly and include uncomfortable side effects, and patients must adhere to a regimen of frequent self-injections. Because the formation of new blood vessels (a process called angiogenesis) plays an important role in the growth of many cancers including Kaposi's sarcoma, researchers are studying natural and synthetic angiogenesis inhibitors in the treatment of AIDS-associated Kaposi's sarcoma. In the past few years, researchers at Memorial Sloan-Kettering, in collaboration with the AIDS Malignancy Consortium, have studied several experimental drugs, including COL-3, which was shown to be effective in some patients with Kaposi's sarcoma.2 Investigational ApproachesResearchers at Memorial Sloan-Kettering are involved in studies developed and conducted by the AIDS Malignancy Consortium to evaluate new treatments for Kaposi's sarcoma. One study evaluated the effectiveness of imatinib mesylate (Gleevec®) -- a drug used to treat chronic myelogenous leukemia and a rare form of sarcoma called gastrointestinal stromal tumor (GIST) -- for the treatment of Kaposi's sarcoma. We are also analyzing the results of a study of the effectiveness of halofuginone, which is a drug applied as an ointment to Kaposi's sarcoma lesions and is thought to inhibit angiogenesis by decreasing the production of enzymes required for blood vessel and tumor cell growth and invasion. We have recently started a pilot study of a drug called rapamycin (sirolimus), which is a drug used in kidney transplant patients to prevent graft rejection following the transplant. Using rapamycin has led to shrinkage of Kaposi's sarcoma tumors in some patients with kidney transplants. Another study under development by the AIDS Malignancy Consortium will investigate a new drug called PTC299. PTC299 inhibits the production of a protein called VEGF, which stimulates the growth of Kaposi's sarcoma. In addition, we are currently studying how to influence HHV-8, the virus that causes lesions. A recently completed study by the AIDS Malignancy Consortium showed that valproic acid, a drug used to treat certain neurologic conditions, might affect HHV-8 in ways that could improve treatments for Kaposi's sarcoma. The AIDS Malignancy Consortium is developing a similar approach in a study of bortezomib (Velcade®), a drug already approved for treatment of multiple myeloma.3 4 5 1S. E. Krown, F. X. Real, S. Cunningham-Rundles, P. L. Myskowski, B. Koziner, S. Fein, A. Mittleman, H. F. Oettgen, and B. Safai, Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's sarcoma, New England Journal of Medicine 308, 1983: 1071-1076. [PubMed Abstract] 2B. J. Dezube, S. E. Krown, J. Y. Lee, K. S. Bauer and D. M. Aboulafia, Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a randomized phase II AIDS Malignancy Consortium Study, Journal of Clinical Oncology 24(9), 2006: 1389-94. [PubMed Abstract] 3A. Noy, D. T. Scadden, J. Lee, B. J. Dezube, D. Aboulafia, A. Tulpule, S. Walmsley, and P. Gill, Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team, Journal of Clinical Oncology 23(5), 2005: 990-8. [PubMed Abstract] 4S. E. Krown, J. Y. Lee, R. A. Ambinder, and J. H. Von Roenn, Interferon-[alpha]2b with protease inhibitor-based therapy in patients with AIDS-related Kaposi's sarcoma: an AIDs Malignancy Consortium phase I trial, JAIDS 41(2), 2006: 149-53. [PubMed Abstract] 5S. A. Miles, B. J. Dezube, J. Y. Lee, S. E. Krown, M. A. Fletcher, M. W. Saville, L. D. Kaplan, J. Groopman, D. T. Scadden, T. Cooley, S. E. Krown, J. Von Roenn, and A. Friedman-Kien, for the AIDS Malignancy Consortium, Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma, AIDS 16(3), 2002: 421-429. [PubMed Abstract] |
