Liposomal chemotherapy

Researchers have developed new, less toxic formulations of chemotherapy drugs. Two such drugs, liposomal doxorubicin and liposomal daunorubicin (DaunoXome), are now licensed in the United Kingdom and are considered to be the standard of care for KS.

Liposomes are microscopic bubbles of fat that enclose drug molecules. These have several theoretical advantages. The liposomes circulate in the bloodstream without releasing the drug. The drug is only released when the liposome leaves the bloodstream and lodges in the body tissues. This is most likely to happen within KS lesions, because the lesions are made up of a mass of abnormally growing blood vessels that are very 'leaky'. Thus, the chemotherapy is targeted to the lesions, wherever they are in the body, with less of the drug affecting non-cancerous areas and thus fewer side-effects.

In Europe liposomal doxorubicin is licensed for the treatment of KS among people with CD4 cell counts below 200 cells/mm3 and extensive skin or visceral lesions, either as first-line or salvage therapy. It has been shown to be more effective than the combination of bleomycin and vincristine as initial treatment for KS, and less toxic. The recommended dose is 20mg/m2 every two to three weeks. About 90% of treated people tend to have a stabilisation or some reduction in the number or size of their KS lesions. This is difficult to compare with other trials as different methods are often used to measure the tumour burden (number, size and location of tumours).

One trial that compared standard chemotherapy and pegylated liposomal doxorubicin found the latter was the superior treatment.1 Furthermore, a Spanish study has shown that adding liposomal doxorubicin to a HAART regimen increases the rate of partial or complete remission of moderate or severe KS.2

The major side-effect is bone marrow suppression, which occurs in around 50% of people, leading to leukopenia, anaemia or thrombocytopenia. Other side-effects may include inflammation of the mouth (stomatitis) and hair loss. These are side-effects seen with the parent drug doxorubicin. However, doxorubicin's most serious side-effect of damage to the heart muscle is far less likely with the liposomal form. Some recipients have developed ulcers on the hands and feet, known as hand-foot syndrome. Neutropenia caused by liposomal doxorubicin or other drugs can be treated with an agent such as granulocyte colony stimulating factor (G-CSF), which promotes the growth of white blood cells.

Liposomal daunorubicin, is used to treat KS, with similar response rates to liposomal doxorubicin. It is approved in the United Kingdom for initial treatment of advanced KS, as an alternative to combination chemotherapy regimens.

A comparative analysis of clinical trial data of the two products found liposomal doxorubicin to be more effective than daunorubicin, with response rates of 59 and 25%. There have been anecdotal reports that people who have stopped responding to one liposomal drug may benefit from switching to the other.

References

  1. Northfelt DW et al. Pegylated 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: 2445-2451, 1998
  2. Martin-Carbonero L et al. Pegylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi's sarcoma. AIDS 18: 1737-1739, 2004