AIDS-Associated Cancers: Diagnosis & Treatment at Memorial Sloan Kettering

Physicians diagnose Kaposi’s sarcoma by biopsy. They obtain a small, disk-shaped tissue sample from a lesion using a sharp, hollow device (called a punch biopsy), or they remove an entire lesion (called an excisional biopsy). A pathologist then examines the tissue under a microscope.

When Kaposi’s sarcoma occurs internally, doctors can sometimes see the lesions and obtain samples by inserting a flexible tube through the esophagus and stomach (endoscopy), the colon (colonoscopy), or the trachea and lung passages (bronchoscopy).

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 drugs to control the HIV infection, as well as therapies to prevent and promptly treat any infections that occur.

Treatments that reduce levels of the virus that causes 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, 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

Cryotherapy
In cryotherapy, doctors use liquid nitrogen to freeze lesions, which then blister, scab, and eventually slough off. This treatment usually leaves minimal marks on light-skinned people, but often causes loss of pigmentation (white spots) on those with darker skin. Laser surgery is also sometimes used to treat Kaposi’s sarcoma lesions.

Radiation Therapy
Physicians may use radiation therapy to treat Kaposi’s sarcoma, particularly if the lesions are large and bulky or cause pain. Radiation is used to treat lesions on the skin and oral cavity more often than those that develop on the internal organs.

Local Chemotherapy
A gel containing alitretinoin (a derivative of vitamin A) was approved by the FDA in 1999 for topical application on Kaposi’s sarcoma lesions. In the past, doctors treated lesions with injections of a chemotherapy drug (an approach called intralesional chemotherapy), but they rarely use this treatment now because it is quite painful and can lead to scarring.

Systemic Therapy

When a patient has many lesions, especially those that affect the internal organs or cause swelling, chemotherapy drugs may be needed. The most commonly used drugs are liposomal doxorubicin and paclitaxel given through a vein.

Physicians at Memorial Sloan Kettering began using the biological therapy drug interferon alpha to treat Kaposi’s sarcoma in the early 1980s.(1) This drug inhibits some of the proteins that make Kaposi’s sarcoma cells divide and survive, and in laboratory experiments it inhibits both HIV and HHV-8 as well. Responses to interferon alpha can occur slowly and patients often experience side effects.

Investigational Approaches

Researchers at Memorial Sloan Kettering are involved in developing and conduction studies developed performed with support from the National Cancer Institute’s 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 — for the treatment of Kaposi’s sarcoma.(2) Drugs like imatinib might work in Kaposi’s sarcoma because they block a set of proteins needed to create these lesions.

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.

One such drug is halofuginone, which is applied as an ointment to Kaposi’s sarcoma lesions. Halofuginone is thought to inhibit angiogenesis by decreasing the production of enzymes required for blood vessel and tumor cell growth and invasion. Another drug under investigation is PTC299, a drug that inhibits the production of a protein called VEGF, which stimulates angiogenesis and the growth of Kaposi’s sarcoma. The group is also developing a study to test lenalidomide, a drug that has many effects on immune function and angiogenesis, as a potential treatment for Kaposi’s sarcoma.

We have completed 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. Rapamycin has led to shrinkage of Kaposi’s sarcoma tumors in some patients with kidney transplants.

In addition, we are currently studying how to influence HHV-8, the virus that causes lesions. A recently completed study 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)

  1. S. 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.
  2. B. 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.
  3. A. 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.
  4. S. 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.
  5. S. 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.