Kaposi's Sarcoma: DaunoXome« Approved

DaunoXome, a liposomal form of the cancer chemotherapy drug daunorubicin, was approved by the FDA on April 8, and became available from distributors in the first week of May. It is approved as first-line chemotherapy for patients with advanced HIV-related KS -- and NOT recommended for less than advanced KS. Its main advantage is reduction in certain side effects compared with conventional chemotherapy.

Liposomal drugs are formulations in which the active chemical is enclosed in microscopic globules of fat. This can improve the targeting of certain drugs, causing more to be delivered to the tumor where it is needed, and less to go elsewhere in the body where it can cause side effects. Liposomal drugs tend to target both KS lesions and cancer tumors; the reason why is not known, but it is suspected that the liposomes leak out of defective blood vessels which grow in the lesions or tumors. (DaunoXome is also being tested for various cancers; at this time it is approved only for KS, although physicians can use it "off label" for other purposes.)

DaunoXome, which is being marketed by NeXstar Pharmaceuticals of San Dimas, California, is the second liposomal chemotherapy drug approved; the first, DOXIL(R), which is liposomal doxorubicin (it is named DOX-SL outside the U.S.), was approved in late 1995 (see AIDS TREATMENT NEWS #236). The two drugs have not been tested head-to-head in a trial, and are not likely to be, so there are no data comparing them. One major difference is that DaunoXome has been approved for first-line use, while DOXIL has been approved for KS patients who have failed standard chemotherapy.

Also, DaunoXome is been priced less than DOXIL; according to NeXstar, its price is comparable to that of standard chemotherapy. This cost advantage is partly offset by the fact that DOXIL is infused once every three weeks, while DaunoXome is infused once every two weeks, increasing the total infusion cost. NeXstar has a patient-assistance program to help in paying for the treatment; for more information (or to enroll), patients, physicians, or social workers can call 800/226-2056.

The major acute toxicity of DaunoXome is bone-marrow suppression -- especially loss of granulocytes (including neutropenia, which can lead to serious or life-threatening infections); blood tests are necessary so that treatment can be interrupted if required.

With the conventional form of daunorubicin, the most serious long-term risk is cumulative heart toxicity. This appears to be much less of a problem with the liposomal form of the drug. But because it is possible, the DaunoXome package insert begins with a prominent warning to monitor for possible heart toxicity -- especially for patients who are at risk, due to previous heart problems or previous use of this class of drug.

Many but not all side effects are less with DaunoXome than with the conventional chemotherapy most likely to be used instead (ABV, which is a combination of Adriamycin (doxorubicin), bleomycin, and vincristine). For example, neuropathy was reduced from 38% to 12%, and hair loss from 36% to 8%, in the major phase III trial which compared DaunoXome to ABV in a total of 227 patients.

Since chemotherapy is not a cure for KS, treatment may need to be continued indefinitely, or for as long as the drug continues to work.