First Line

A treatment for advanced HIV-associated Kaposi’s sarcoma is relaunched
by Chael Needle

Newly acquired by Galen from Gilead Sciences, DaunoXome (daunorubicin citrate liposome injection) is an anthracycline chemotherapy agent indicated for advanced HIV-associated Kaposi’s sarcoma (KS). First approved in the United States in 1996, DaunoXome is only recently back on the market.

Associated with the human herpes virus 8, KS is a common malignancy affecting the skin and internal organs. It is the most prevalent HIV-associated malignancy worldwide, affecting up to twenty percent of people with AIDS who are not on antiretrovirals. The cancer mostly affects men.

In the early days of the pandemic the red and purple patches on the skin, one of the symptoms of KS, became perhaps the best known of all the AIDS-defining illnesses. KS became less common in the nineties in developed countries as improved AIDS treatments became available. KS is re-emerging aggressively, however, and treatments are needed. In a September 2007 article published in the International Journal of Nanomedicine, Christin E. Petre and Dirk P. Dittmer state: “Yet, even today, less than 50% of all KS patients in the US, i.e., with ready access to HAART, reach the 5-year survival mark. The outlook is even worse for the growing number of African American KS patients.”

For some patients, treatment with HAART and its effects on the immune system keep KS from developing or at bay. Those patients fall into the first of two broad categories of AIDS-related Kaposi’s sarcoma patients, says oncologist Anil Tulpule, MD, Associate Professor of Medicine, at the Norris Cancer Center in Los Angeles. He explains: “When we first see a patient, if the patient has lesions only on the skin and fewer than ten to twenty lesions, with no associated edema or swelling and [with no] lymph node, lung, or GI tract involvement (those are the extra skin involvements), they fall into a category called limited disease and these are patients whom we can just treat with HAART. And their disease either stabilizes or even responds.”

He explains the other category: “If the patients have any one of the following: more than twenty lesions, or if the disease grows at a pace of more than ten new skin lesions per month, or if they have gastrointestinal, lung, or lymph node involvement, or if their skin lesions are associated with edema—these are the patients classified as having disseminated disease. And unfortunately this cannot be controlled with HAART alone. So these are the patients who need chemotherapy and DaunoXome is a first-line chemotherapy drug for these patients.”

DaunoXome has a delivery system different than other conventional anthracyclines. Encapsulated in a protective coating called a liposome, the drug molecules remain in the body longer, and thus more of the treatment is delivered to cancer cells. “The first treatment for KS was a combination of doxorubicin, bleomycin, and vincristine—we used to call it the ABV combination. This combination was restrictive by the side effects of each drug,” says Dr. Tulpule. “ABV combination in a Phase III study was compared to DaunoXome as a single agent. This study was published in 1996. The conclusion was that the efficacy of DaunoXome as a single agent was comparable to the ABV combination. So it was like using one drug instead of three drugs with comparative efficacy.”

DaunoXome can also produce negative side effects, including a decrease in the production of blood cells, resulting in a suppressed immune system and an increased susceptibility to infections, and cardiac toxicity and congestive heart failure, among others.

In conclusion, Dr. Tulpule commented on the need for DaunoXome in resource-limited settings. “What has happened in the past is DaunoXome has been the first-line treatment for patients who need chemotherapy and Taxol is traditionally the second-line agent for people who fail DaunoXome or Doxil, another liposomal anthracycline. DaunoXome has not been available for a couple of years now. Recently Doxil was not available; I’ve heard that is also being made available now. What has happened is we have had to treat these patients with Taxol, which we would have otherwise reserved as a second-line. So what I am saying is that we’ve had to burn our bridge, so to speak…So, yes, there has been a void which we would love to be filled.”

Chael Needle wrote about education and advocacy Web site, in the February issue.

April 2012